IONIS PHARMACEUTICALS INC
10-Ks and 10-Qs
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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549
Form
10-Q
(Mark One)
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QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
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For the Quarterly Period Ended
March 31, 2025
OR
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TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF SECURITIES EXCHANGE ACT OF 1934
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For the transition period from _____ to _____
Commission file number
000-19125
(Exact name of Registrant as specified in its charter)
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(State or other jurisdiction of incorporation or organization)
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(IRS Employer Identification No.)
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(Address of Principal Executive Offices)
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(Zip Code)
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(Registrant’s telephone number, including area code)
Securities registered pursuant to Section 12(b) of the Act:
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Title of each class
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Trading symbol
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Name of each exchange on which registered
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||
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“
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The
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Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities
Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.
Yes
☒
No
☐
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted and posted
pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).
Yes
☒
No
☐
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller
reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
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Accelerated Filer
☐
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Non-accelerated Filer
☐
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Smaller Reporting Company
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Emerging Growth Company
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If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for
complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
☐
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12(b)-2 of the Securities Exchange Act of 1934). Yes
☐
No
☒
The number of shares of voting common stock outstanding as of April 24, 2025 was
159,159,099
.
FORM 10-Q
INDEX
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PART I
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FINANCIAL INFORMATION
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ITEM 1:
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Financial Statements:
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3
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||
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Condensed Consolidated
Statements of Operations
for the
three months
ended
March 31, 2025
and
2024
(unaudited)
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4
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Condensed Consolidated
Statements of Comprehensive Loss
for the
three months
ended
March 31, 2025
and
2024
(unaudited)
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5
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Condensed Consolidated Statements of
Stockholders’ Equity
for the
three months
ended
March 31, 2025
and
2024
(unaudited)
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6
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Condensed Consolidated Statements of
Cash Flows
for the
three
months ended
March 31, 2025
and
2024
(unaudited)
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7
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8
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||
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ITEM 2:
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||
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22
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||
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24
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25
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||
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30
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||
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ITEM 3:
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32
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ITEM 4:
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32
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PART II
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33
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ITEM 1:
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33
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ITEM 1A:
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33
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ITEM 2:
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51
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ITEM 3:
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51
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ITEM 4:
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51
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ITEM 5:
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51
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ITEM 6:
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51
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52
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TRADEMARKS
“
Ionis,” the Ionis logo, and other
trademarks or service marks of Ionis Pharmaceuticals, Inc. appearing in this report are the property of Ionis Pharmaceuticals, Inc. “Akcea,” the Akcea logo, and other trademarks or service marks of Akcea Therapeutics, Inc. appearing in this report are
the property of Akcea Therapeutics, Inc., Ionis’ wholly owned subsidiary. This report contains additional trade names, trademarks and service marks of others, which are the property of their respective owners. Solely for convenience, trademarks and
trade names referred to in this report may appear without the ® or TM symbols.
PART I — FINANCIAL INFORMATION
| ITEM 1. |
FINANCIAL STATEMENTS
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CONDENSED CONSOLIDATED BALANCE SHEETS
(in thousands, except share data)
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March 31,
2025
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December 31
,
2024
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|||||||
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(unaudited)
|
||||||||
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ASSETS
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||||||||
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Current assets:
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||||||||
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Cash and cash equivalents
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$
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$
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||||
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Short-term investments
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||||||
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Contracts receivable
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||||||
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Inventories
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||||||
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Other current assets
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||||||
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Total current assets
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||||||
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Property, plant and equipment, net
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||||||
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Right-of-use assets
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||||||
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Deposits and other assets
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||||||
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Total assets
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$
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$
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||||
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LIABILITIES AND STOCKHOLDERS’ EQUITY
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||||||||
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Current liabilities:
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||||||||
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Accounts payable
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$
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$
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||||
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Accrued compensation
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||||||
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Accrued liabilities
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||||||
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Income taxes payable
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||||||
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Current portion of deferred contract revenue
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||||||
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Other current liabilities
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||||||
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Total current liabilities
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||||||
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Long-term deferred contract revenue
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||||||
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||||||
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Liability related to sale of future royalties, net
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||||||
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Long-term lease liabilities
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||||||
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Long-term obligations
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Total liabilities
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||||||
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Stockholders’ equity:
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||||||||
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Common stock, $
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||||||
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Additional paid-in capital
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||||||
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Accumulated other comprehensive loss
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(
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)
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(
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)
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||||
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Accumulated deficit
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(
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)
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(
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)
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||||
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Total stockholders’ equity
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||||||
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Total liabilities and stockholders’ equity
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$
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$
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||||
See accompanying notes.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(in thousands, except for per share amounts)
(Unaudited)
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Three Months Ended
March 31,
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||||||||
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2025
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2024
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|||||||
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Revenue:
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||||||||
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Commercial revenue:
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||||||||
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Product sales, net
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$
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$
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Royalty revenue
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Other commercial revenue
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||||||
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Total commercial revenue
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Research and development revenue:
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||||||||
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Collaborative agreement revenue
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WAINUA joint development revenue
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||||||
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Total research and development revenue
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Total revenue
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||||||
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Expenses:
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||||||||
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Cost of sales
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Research, development and patent
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Selling, general and administrative
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||||||
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Total operating expenses
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||||||
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Loss from operations
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(
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)
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(
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)
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||||
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Other income (expense):
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||||||||
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Investment income
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||||||
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Interest expense
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(
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)
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(
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)
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||||
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Interest expense related to sale of future royalties
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(
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)
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(
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)
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||||
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Gain (loss) on investments
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(
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)
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|||||
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Other income
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||||||
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Loss before income tax expense
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(
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)
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(
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)
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||||
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Income tax expense
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(
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)
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(
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)
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||||
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Net loss
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$
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(
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)
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$
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(
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)
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||
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Basic and diluted net loss per share
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$
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(
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)
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$
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(
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)
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||
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Shares used in computing basic and diluted net loss per share
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|
||||||
See accompanying notes.
CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS
(in thousands)
(Unaudited)
|
Three Months Ended
March 31,
|
||||||||
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2025
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2024
|
|||||||
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Net loss
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$
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(
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)
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$
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(
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)
|
||
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Unrealized gains (losses) on debt securities, net of tax
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(
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)
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|||||
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Currency translation adjustment
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(
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)
|
|||||
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Comprehensive loss
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$
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(
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)
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$
|
(
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)
|
||
See accompanying notes.
CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS
’
EQUITY
(in thousands)
(Unaudited)
|
Common Stock
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Additional
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Accumulated Other
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Accumulated
|
Total
Stockholders
’
|
||||||||||||||||||||
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Description
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Shares
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Amount
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Paid in Capital
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Comprehensive Loss
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Deficit
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Equity
|
||||||||||||||||||
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Balance at
December 31, 2023
|
|
$
|
|
$
|
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$
|
(
|
)
|
$
|
(
|
)
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$
|
|
|||||||||||
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Net loss
|
—
|
|
|
|
(
|
)
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(
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)
|
||||||||||||||||
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Change in unrealized losses, net of tax
|
—
|
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(
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)
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(
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)
|
||||||||||||||||
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Foreign currency translation
|
—
|
|
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(
|
)
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(
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)
|
||||||||||||||||
|
Issuance of common stock in connection with employee stock plans, net
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|
||||||||||||||||||
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Stock-based compensation expense
|
—
|
|
|
|
|
|
||||||||||||||||||
|
Balance at
March 31, 2024
|
|
$
|
|
$
|
|
$
|
(
|
)
|
$
|
(
|
)
|
$
|
|
|||||||||||
|
Balance at
December 31, 2024
|
|
$
|
|
$
|
|
$
|
(
|
)
|
$
|
(
|
)
|
$
|
|
|||||||||||
|
Net loss
|
—
|
|
|
|
(
|
)
|
(
|
)
|
||||||||||||||||
|
Change in unrealized gains, net of tax
|
—
|
|
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|
|
|
||||||||||||||||||
|
Foreign currency translation
|
—
|
|
|
|
|
|
||||||||||||||||||
|
Issuance of common stock in connection with employee stock plans, net
|
|
|
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|
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|
||||||||||||||||||
|
Stock-based compensation expense
|
—
|
|
|
|
|
|
||||||||||||||||||
|
Balance at
March 31, 2025
|
|
$
|
|
$
|
|
$
|
(
|
)
|
$
|
(
|
)
|
$
|
|
|||||||||||
See accompanying notes.
CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(in thousands)
(Unaudited)
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Operating activities:
|
||||||||
|
Net loss
|
$
|
(
|
)
|
$
|
(
|
)
|
||
|
Adjustments to reconcile net loss to net cash used in operating activities:
|
||||||||
|
Depreciation
|
|
|
||||||
|
Amortization of right-of-use operating lease assets
|
|
|
||||||
|
Amortization of other assets
|
|
|
||||||
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Amortization of discount on investments, net
|
(
|
)
|
(
|
)
|
||||
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Amortization of debt issuance costs
|
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|
||||||
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Non-cash royalty revenue related to sale of royalties
|
(
|
)
|
(
|
)
|
||||
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Non-cash interest related to sale of future royalties
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|
||||||
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Stock-based compensation expense
|
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|
||||||
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Loss (gain) on investments
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|
(
|
)
|
|||||
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Non-cash losses related to other assets
|
|
|
||||||
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Changes in operating assets and liabilities:
|
||||||||
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Contracts receivable
|
|
|
||||||
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Inventories
|
|
|
||||||
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Other current and long-term assets
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(
|
)
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|
|||||
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Accounts payable
|
(
|
)
|
(
|
)
|
||||
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Income taxes
|
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|
||||||
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Accrued compensation
|
(
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)
|
(
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)
|
||||
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Accrued liabilities and other current liabilities
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|
(
|
)
|
|||||
|
Deferred contract revenue
|
(
|
)
|
(
|
)
|
||||
|
Net cash used in operating activities
|
(
|
)
|
(
|
)
|
||||
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Investing activities:
|
||||||||
|
Purchases of short-term investments
|
(
|
)
|
(
|
)
|
||||
|
Proceeds from sale of short-term investments
|
|
|
||||||
|
Purchases of property, plant and equipment
|
(
|
)
|
(
|
)
|
||||
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Acquisition of licenses and other assets, net
|
(
|
)
|
(
|
)
|
||||
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Net cash provided by investing activities
|
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|
||||||
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Financing activities:
|
||||||||
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Proceeds from issuance of common stock through equity plans, net
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|
||||||
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Principal payments on mortgage debt
|
(
|
)
|
(
|
)
|
||||
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Net cash provided by financing activities
|
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|
||||||
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Effects of exchange rates on cash
|
|
(
|
)
|
|||||
|
Net increase (decrease) in cash and cash equivalents
|
|
(
|
)
|
|||||
|
Cash and cash equivalents at beginning of period
|
|
|
||||||
|
Cash and cash equivalents at end of period
|
$
|
|
$
|
|
||||
|
Supplemental disclosures of cash flow information:
|
||||||||
|
Interest paid
|
$
|
|
$
|
|
||||
|
Income taxes paid (refunds received)
|
$
|
(
|
)
|
$
|
|
|||
|
Supplemental disclosures of non-cash investing and financing activities:
|
||||||||
|
Amounts accrued for capital and patent expenditures
|
$
|
|
$
|
|
||||
See accompanying notes.
NOTES TO CONDENSED CONSOLIDATED FINANCIAL STATEMENTS
March 31, 2025
(Unaudited)
1. Organization and Basis of Presentation
Organization and Business Activity
We incorporated in California on January 10, 1989. In conjunction with our initial public offering, we reorganized as a Delaware
corporation in April 1991. We are a leader in the discovery and development of RNA-targeted therapeutics.
Basis of Presentation
We prepared the unaudited interim condensed consolidated financial statements for the three months ended March 31, 2025 and 2024 on the same basis as the audited financial statements for the year ended December 31, 2024. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at
such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these
financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2024
included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.
In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned
subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (“we”, “us” or “our”).
We operate as a
segment, Ionis operations, because our chief operating decision maker, or CODM, reviews operating results on an aggregate basis and manages our operations as a
operating segment. Refer to Note 14,
Segment Information
, for further details on our segment information.
Use of Estimates
We prepare our condensed consolidated financial statements in
conformity with accounting principles generally accepted in the United States, or
U.S., that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying
notes. Actual results could differ from our estimates.
2. Significant Accounting Policies
Below, we have included our accounting policies for revenue recognition related to product sales, net and cost of sales as a result of our
launch of TRYNGOLZA in the U.S. Our other significant accounting policies have not changed substantially from those included in our Annual Report on Form 10-K for the year ended December 31, 2024.
Revenue Recognition
Product Sales, Net
We recognize revenue from product sales when the customer obtains control of our product in the amount of the transaction price, which is
the amount that reflects the consideration which we expect to receive. We estimate reserves for variable consideration related to applicable discounts, rebates, chargebacks and other allowances included in our agreements with customers, payors and
other third parties. We include the amount of variable consideration in the transaction price to the extent that it is probable that a significant reversal in the amount of the cumulative revenue recognized will not occur in a future period. If actual
results vary significantly from our estimates, we adjust our estimates in the period that we become aware of such variances.
Cost of Sales
Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs
and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales.
Cost of sales for a newly launched product, such as TRYNGOLZA, does not include the full cost of manufacturing until we manufacture and
sell additional inventory after exhausting pre-launch inventory, which we previously recorded as research and development, or R&D, expense.
Recent Accounting Standards
In November 2023, the Financial Accounting Standards Board, or FASB, issued Accounting Standard Update, or ASU, 2023-07, which provides
updated guidance on segment reporting. The guidance requires public companies to disclose significant expenses that are regularly provided to the CODM, other segment items for each reportable segment and measures of segment profit or loss used by the
CODM for allocating resources. In addition, the updated guidance requires public companies with a single reportable segment to provide all disclosures required under Accounting Standards Codification, or ASC, Topic 280,
Segment Reporting
, and public companies to include in interim reports all disclosures related to a reportable segment’s profit or loss and assets that are currently required in
annual reports. We adopted the reporting requirements in our 2024 Annual Report on Form 10-K and in this Quarterly Report on Form 10-Q for the first quarter of 2025. Refer to Note 14,
Segment Information
, for further details on our segment information.
We do not expect any recently issued accounting standards other than those included in our Annual Report on Form 10-K for the year ended December 31, 2024 to have a material impact to our financial results.
3. Supplemental Financial Data
Inventories
Our inventories consisted of the following (in thousands):
|
March 31, 2025
|
December 31, 2024
|
|||||||
|
Raw materials
|
$
|
|
$
|
|
||||
|
Work in process
|
|
|
||||||
|
Finished goods
|
|
|
||||||
|
Total inventories
|
$
|
|
$
|
|
||||
Accrued Liabilities
Our accrued liabilities consisted of the following (in thousands):
|
March 31, 2025
|
December 31, 2024
|
|||||||
|
Clinical expenses
|
$
|
|
$
|
|
||||
|
In-licensing expenses
|
|
|
||||||
|
Commercial expenses
|
|
|
||||||
|
Other miscellaneous expenses
|
|
|
||||||
|
Total accrued liabilities
|
$
|
|
$
|
|
||||
4. Revenues
During the three months ended March 31, 2025 and 2024, our revenues were comprised of the
following (in thousands):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Revenue:
|
||||||||
|
Commercial revenue:
|
||||||||
|
Product sales, net:
|
||||||||
|
TRYNGOLZA sales, net
|
$
|
|
$
|
|
||||
|
Total product sales, net
|
|
|
||||||
|
Royalty revenue:
|
||||||||
|
SPINRAZA royalties
|
|
|
||||||
|
WAINUA royalties
|
|
|
||||||
|
Other royalties
|
|
|
||||||
|
Total royalty revenue
|
|
|
||||||
|
Other commercial revenue:
|
||||||||
|
TEGSEDI and WAYLIVRA revenue, net
|
|
|
||||||
|
Other revenue
|
|
|
||||||
|
Total other commercial revenue
|
|
|
||||||
|
Total commercial revenue
|
|
|
||||||
|
Research and development revenue:
|
||||||||
|
Collaborative agreement revenue
|
|
|
||||||
|
WAINUA joint development revenue
|
|
|
||||||
|
Total research and development revenue
|
|
|
||||||
|
Total revenue
|
$
|
|
$
|
|
||||
Revenue Sources
The following are sources of revenue and when we typically recognize revenue.
Commercial Revenue
In December 2024, the U.S. Food and Drug Administration, or FDA, approved TRYNGOLZA (olezarsen) for the treatment of familial
chylomicronemia syndrome, or FCS. Following the approval, we launched TRYNGOLZA and began earning revenue from TRYNGOLZA sales. We recognize product sales, net of variable considerations related to applicable discounts and allowances, when the customer
obtains control of our product.
We earn royalty payments primarily on net sales of SPINRAZA, WAINUA and QALSODY.
We earn commercial revenue from TEGSEDI and WAYLIVRA sales under our distribution agreements with Swedish Orphan Biovitrum AB, or Sobi. In
addition, we receive royalties from PTC Therapeutics International Limited, or PTC, for TEGSEDI and WAYLIVRA sales. Refer to Part IV, Item 15, Note 4,
Collaborative
Arrangements and Licensing Agreements
, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 for details on our commercialization partnerships with Sobi and PTC.
Research and development revenue under collaboration agreements
We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration
agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, R&D services and manufacturing services.
For R&D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the
effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period,
relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make
numerous estimates that may involve judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.
Upfront payments:
When we
enter into a collaboration agreement and receive an upfront payment, we record the entire upfront payment as deferred revenue if our only performance obligation is for R&D services we will provide in the future. We amortize the upfront payment into
revenue as we perform the R&D services. If part or all of the upfront payment is a license fee, we recognize as revenue the portion related to the license when we deliver the license to our partner because our partner has full use of the license
and we do not have any additional performance obligations related to the license after delivery.
Milestone payments:
We
consider milestone payments to be variable consideration and include them in the transaction price when it is probable. We typically include milestone payments for R&D services in the transaction price when they are achieved. We include these
milestone payments when they are achieved because there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include regulatory milestone payments in the transaction price once the medicine is
approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting rules.
We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, when we
achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&D services performance obligation and
recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone payment to the
transaction price.
Conversely, we recognize in full those milestone payments that we earn based on our partners’ activities when our partner achieves the
milestone event and we do not have a remaining performance obligation.
License fees:
We recognize
as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner because our partner has full use of the license and we do not have any additional performance obligations
related to the license after delivery.
WAINUA (Eplontersen) Collaboration with AstraZeneca
In 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize WAINUA for the
treatment of transthyretin amyloidosis, or ATTR. Under the terms of the agreement, we received a $
200
million upfront payment in 2021.
We evaluated our WAINUA collaboration under ASC Topic 808,
Collaborative Arrangements
, or ASC 808, and identified
four
material components: (i) the license we granted to
AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are
performing.
We determined that we had a vendor-customer relationship within the scope of ASC Topic 606,
Revenue from Contracts with Customers
, or ASC 606, for the license we granted to AstraZeneca and as a result we had
one
performance obligation. For our sole performance obligation, we determined the transaction price was the $
200
million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations after we delivered the
license to AstraZeneca.
We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
the scope of ASC 808, because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is currently responsible for
55
percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an
accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca’s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible
for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing WAINUA to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related
to commercial and medical affairs activities as reductions of our selling, general and administrative, or SG&A, expense and R&D expense, respectively.
Swedish Orphan Biovitrum AB (Sobi)
Under our distribution agreements with Sobi, we concluded that our performance obligation is to provide services to Sobi over the term of
the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We
view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize
distribution fee revenue based on Sobi’s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.
5. Collaborative Arrangements and Licensing Agreements
Below, we have included our Ono collaboration, which is the
only collaboration that had either substantive changes or was new from those included in Part IV, Item 15, Note 4,
Collaborative Arrangements and
Licensing Agreements
, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024.
Ono
In March 2025, we entered into an agreement with Ono Pharmaceutical, Ltd, or Ono, to develop and commercialize sapablursen, an
investigational RNA-targeted medicine for the potential treatment of polycythemia vera, or PV, a rare and potentially life-threatening hematologic disease. We are responsible for completing the ongoing Phase 2 IMPRSSION study, while Ono will be solely
responsible for subsequent development, regulatory filings and commercialization of sapablursen.
Over the term of our sapablursen collaboration, we are eligible to receive up to $
940
million, which is comprised of a $
280
million upfront payment and up
to $
660
million in development, regulatory and sales milestone payments. In addition, we are eligible to receive royalties in the mid-teen
percentage range on net sales.
In April 2025, we achieved a $
280
million upfront payment when this transaction received clearance under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, or HSR Act.
6. Basic and Diluted Net Loss Per Share
Basic net loss per share
We calculated our basic net loss per share for the three months ended March 31, 2025 and 2024 by dividing our net loss by our weighted-average number of common shares outstanding during the period.
Diluted net loss per share
For the three months ended March 31, 2025 and 2024, we incurred a net
loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss
per share:
| ● |
|
| ● |
|
| ● |
Note hedges related to the
|
| ● |
Dilutive stock options;
|
| ● |
Unvested restricted stock units, or RSUs;
|
| ● |
Unvested performance restricted stock units, or PRSUs; and
|
| ● |
Employee Stock Purchase Plan, or ESPP.
|
For the three months ended March 31, 2024, common stock underlying the
0.125
percent
convertible senior notes, or
0.125
%
Notes
, and n
ote hedges related to the
0.125
%
Notes
would also have had an anti-dilutive effect on net loss per share.
Additionally, as of March 31, 2025
and 2024, we had warrants related to our
0
%
and
0.125
% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when
the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.
7. Investments
The following table summarizes the contract maturity of the available-for-sale securities we held as of March 31, 2025:
|
|
|
%
|
||
|
After
|
|
%
|
||
|
After
|
|
%
|
||
|
Total
|
|
%
|
As illustrated above, at March 31, 2025,
94
percent of our available-for-sale securities had a maturity of less than
two years
.
All of our available-for-sale debt securities are available to us for use in our current operations. As a result, we categorize all of
these securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date.
We invest in debt securities
with strong credit
ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard & Poor’s, Moody’s or Fitch, respectively.
At March 31, 2025, we had an
equity ownership interest of less than 20 percent in
seven
private companies and
three
public companies with which we conduct business.
The following is a summary of our investments (in thousands):
|
Amortized
|
Gross Unrealized
|
Estimated
|
||||||||||||||
|
March 31, 2025
|
Cost
|
Gains
|
Losses
|
Fair Value
|
||||||||||||
|
Available-for-sale debt securities:
|
||||||||||||||||
|
Corporate debt securities (1)
|
$
|
|
$
|
|
$
|
(
|
)
|
$
|
|
|||||||
|
Debt securities issued by U.S. government agencies
|
|
|
(
|
)
|
|
|||||||||||
|
Debt securities issued by the U.S. Treasury (1)
|
|
|
(
|
)
|
|
|||||||||||
|
Debt securities issued by states of the U.S. and political subdivisions of the states
|
|
|
|
|
||||||||||||
|
Total debt securities with a maturity of one year or less
|
|
|
(
|
)
|
|
|||||||||||
|
Corporate debt securities
|
|
|
(
|
)
|
|
|||||||||||
|
Debt securities issued by U.S. government agencies
|
|
|
(
|
)
|
|
|||||||||||
|
Debt securities issued by the U.S. Treasury
|
|
|
(
|
)
|
|
|||||||||||
|
Debt securities issued by states of the U.S. and political subdivisions of the states
|
|
|
|
|
||||||||||||
|
Other municipal debt
|
|
|
|
|
||||||||||||
|
Total debt securities with a maturity of more than one year
|
|
|
(
|
)
|
|
|||||||||||
|
Total available-for-sale debt securities
|
$
|
|
$
|
|
$
|
(
|
)
|
$
|
|
|||||||
|
Equity securities:
|
||||||||||||||||
|
Publicly traded equity securities included in other current assets (2)
|
$
|
|
$
|
|
$
|
(
|
)
|
$
|
|
|||||||
|
Privately held equity securities included in deposits and other assets (3)
|
|
|
(
|
)
|
|
|||||||||||
|
Total equity securities
|
|
|
(
|
)
|
|
|||||||||||
|
Total available-for-sale debt and equity securities
|
$
|
|
$
|
|
$
|
(
|
)
|
$
|
|
|||||||
|
Amortized
|
Gross Unrealized
|
Estimated
|
||||||||||||||
|
December 31, 2024
|
Cost
|
Gains
|
Losses
|
Fair Value
|
||||||||||||
|
Available-for-sale debt securities:
|
||||||||||||||||
|
Corporate debt securities (1)
|
$
|
|
$
|
|
$
|
(
|
)
|
$
|
|
|||||||
|
Debt securities issued by U.S. government agencies
|
|
|
(
|
)
|
|
|||||||||||
|
Debt securities issued by the U.S. Treasury (1)
|
|
|
(
|
)
|
|
|||||||||||
|
Debt securities issued by states of the U.S. and political subdivisions of the states
|
|
|
|
|
||||||||||||
|
Total debt securities with a maturity of one year or less
|
|
|
(
|
)
|
|
|||||||||||
|
Corporate debt securities
|
|
|
(
|
)
|
|
|||||||||||
|
Debt securities issued by U.S. government agencies
|
|
|
(
|
)
|
|
|||||||||||
|
Debt securities issued by the U.S. Treasury
|
|
|
(
|
)
|
|
|||||||||||
|
Other municipal debt securities
|
|
|
(
|
)
|
|
|||||||||||
|
Total debt securities with a maturity of more than one year
|
|
|
(
|
)
|
|
|||||||||||
|
Total available-for-sale debt securities
|
$
|
|
$
|
|
$
|
(
|
)
|
$
|
|
|||||||
|
Equity securities:
|
||||||||||||||||
|
Publicly traded equity securities included in other current assets (2)
|
$
|
|
$
|
|
$
|
(
|
)
|
$
|
|
|||||||
|
Privately held equity securities included in deposits and other assets (3)
|
|
|
(
|
)
|
|
|||||||||||
|
Total equity securities
|
|
|
(
|
)
|
|
|||||||||||
|
Total available-for-sale debt and equity securities
|
$
|
|
$
|
|
$
|
(
|
)
|
$
|
|
|||||||
| (1) |
|
| (2) |
|
| (3) |
|
The following is a summary of our investments we consider to be temporarily impaired at March 31, 2025 (in thousands, except for number of investments):
|
Less than 12 Months of
Temporary Impairment
|
More than 12 Months of
Temporary Impairment
|
Total Temporary
Impairment
|
||||||||||||||||||||||||||
|
Number of
Investments
|
Estimated
Fair Value
|
Unrealized
Losses
|
Estimated
Fair Value
|
Unrealized
Losses
|
Estimated
Fair Value
|
Unrealized
Losses
|
||||||||||||||||||||||
|
Corporate debt securities
|
|
$
|
|
$
|
(
|
)
|
$
|
|
$
|
(
|
)
|
$
|
|
$
|
(
|
)
|
||||||||||||
|
Debt securities issued by U.S. government agencies
|
|
|
(
|
)
|
|
|
|
(
|
)
|
|||||||||||||||||||
|
Debt securities issued by the U.S. Treasury
|
|
|
(
|
)
|
|
(
|
)
|
|
(
|
)
|
||||||||||||||||||
|
Debt securities issued by states of the U.S. and political subdivisions of the states
|
|
|
|
|
|
|
|
|||||||||||||||||||||
|
Total temporarily impaired securities
|
|
$
|
|
$
|
(
|
)
|
$
|
|
$
|
(
|
)
|
$
|
|
$
|
(
|
)
|
||||||||||||
We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates
since purchase rather than underlying credit deterioration for any of the issuers. We believe it is more likely than not that we will be able to hold our debt securities with declines in value to maturity. Therefore, we intend to hold these securities
to maturity and anticipate full recovery of our debt securities’ amortized cost basis at maturity.
8. Fair Value Measurements
The following tables present the major security types we held at March 31, 2025 and December 31, 2024 that we regularly measure and
carry at fair value. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective security’s fair value (in thousands):
|
At
March 31, 2025
|
Quoted Prices in
Active Markets
(Level 1)
|
Significant Other
Observable Inputs
(Level 2)
|
||||||||||
|
Cash equivalents (1)
|
$
|
|
$
|
|
$
|
|
||||||
|
Corporate debt securities (2)
|
|
|
|
|||||||||
|
Debt securities issued by U.S. government agencies (3)
|
|
|
|
|||||||||
|
Debt securities issued by the U.S. Treasury (3)
|
|
|
|
|||||||||
|
Debt securities issued by states of the U.S. and political subdivisions of the states (3)
|
|
|
|
|||||||||
|
Other municipal debt (3)
|
|
|
|
|||||||||
|
Publicly traded equity securities included in other current assets (4)
|
|
|
|
|||||||||
|
Total
|
$
|
|
$
|
|
$
|
|
||||||
|
At
December 31, 2024
|
Quoted Prices in
Active Markets
(Level 1)
|
Significant Other
Observable Inputs
(Level 2)
|
||||||||||
|
Cash equivalents (1)
|
$
|
|
$
|
|
$
|
|
||||||
|
Corporate debt securities (3)
|
|
|
|
|||||||||
|
Debt securities issued by U.S. government agencies (3)
|
|
|
|
|||||||||
|
Debt securities issued by the U.S. Treasury (3)
|
|
|
|
|||||||||
|
Debt securities issued by states of the U.S. and political subdivisions of the states (3)
|
|
|
|
|||||||||
|
Other municipal debt securities (3)
|
|
|
|
|||||||||
|
Publicly traded equity securities included in other current assets (4)
|
|
|
|
|||||||||
|
Total
|
$
|
|
$
|
|
$
|
|
||||||
The following footnotes reference lines in our condensed consolidated balance sheets:
| (1) |
|
| (2) |
|
| (3) |
|
| (4) |
|
Convertible Notes
Our
1.75
% Notes and
0
% Notes had a fair value of $
559.0
million and $
623.0
million at March 31, 2025, respectively.
Our
1.75
% Notes and
0
% Notes had a
fair value of $
569.3
million and $
612.8
million at December 31, 2024, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are
Level 2 measurements because the notes do not trade regularly.
9. Stock-based Compensation Expense
The following table summarizes stock-based compensation expense for the three months ended March 31, 2025 and 2024 (in thousands):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Cost of sales
|
$
|
|
$
|
|
||||
|
Research, development and patent expense
|
|
|
||||||
|
Selling, general and administrative expense
|
|
|
||||||
|
Stock-based compensation expense, net of amounts capitalized
|
|
|
||||||
|
Capitalized stock-based compensation expense
|
|
|
||||||
|
Total stock-based compensation expense
|
$
|
|
$
|
|
||||
As of March 31, 2025, total
unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $
51.9
million, $
117.1
million and $
17.8
million, respectively.
Our actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures, including any PRSUs that do not vest. We expect to recognize the cost of stock-based compensation
expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of
1.3
years,
1.8
years and
1.9
years, respectively.
Refer to Part IV, Item 15, Note 1,
Organization
and Significant Accounting Policies
, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 for further details on how we determine the fair value of stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP.
For the three months ended March 31, 2025 and 2024, we used the
following weighted-average assumptions in our Black-Scholes calculations:
Employee Stock Options:
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Risk-free interest rate
|
|
%
|
|
%
|
||||
|
Dividend yield
|
|
%
|
|
%
|
||||
|
Volatility
|
|
%
|
|
%
|
||||
|
Expected life
|
|
|
||||||
ESPP:
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Risk-free interest rate
|
|
%
|
|
%
|
||||
|
Dividend yield
|
|
%
|
|
%
|
||||
|
Volatility
|
|
%
|
|
%
|
||||
|
Expected life
|
|
|
||||||
RSUs:
The weighted-average grant date fair value of RSUs granted to employees for the three months ended March 31, 2025 and 2024 was $
33.21
and $
53.54
per share, respectively.
PRSUs:
Under the terms of the PRSUs we granted in 2025 and 2024,
100
percent of the PRSUs may vest at the end of the
three-year
performance period based on our relative
total shareholder return, or TSR, as compared to a peer group of companies and as measured at the end of the performance period. Under the terms of the grants,
no
number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from
zero
to
200
percent of the target number depending on our
relative TSR.
The weighted-average grant date fair value of PRSUs we granted to our executive officers for the three months ended March 31, 2025 and 2024 was $
48.81
and $
78.41
per share, respectively.
10. Income Taxes
We recorded income tax expense of $
0.1
million for the three months ended March 31, 2025 compared to $
0.1
million for the same period in 2024.
We continue to maintain a full valuation allowance on all of our net deferred tax assets.
11. Liability Related to Sale of Future Royalties
In 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of our
future SPINRAZA and pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. As a result, we received an upfront payment of $
500
million and we are eligible to receive up to $
625
million in additional milestone payments. Under the terms of
the agreement, Royalty Pharma will receive
25
percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to
45
percent of royalty payments in 2028, on up to $
1.5
billion in annual sales. In addition, Royalty Pharma will receive
25
percent of any future royalty payments on pelacarsen, our medicine in
development to treat patients with elevated lipoprotein(a)-driven cardiovascular disease. Royalty Pharma’s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $
475
million or $
550
million, depending on the
timing and occurrence of FDA approval of pelacarsen.
We recorded the upfront payment of $
500
million as a liability related to the sale of future royalties, net of transaction costs of $
10.4
million, which we are amortizing over the
estimated life of the arrangement using the effective interest rate method. We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. We record royalty payments made to Royalty
Pharma as a reduction of the liability.
We determine the effective interest rate used to record interest expense under this agreement based on an estimate of future royalty
payments to Royalty Pharma. As of March 31, 2025 and 2024, the estimated effective interest rate under the agreement was
13.5
percent.
The following table sets forth information on our liability related to sale of future royalties (in thousands):
|
Liability related to sale of future royalties, net as of December 31, 2024
|
$
|
|
||
|
Royalty payments to Royalty Pharma
|
(
|
)
|
||
|
Interest expense related to sale of future royalties
|
|
|||
|
Amortization of issuance costs related to sale of future royalties
|
|
|||
|
Liability related to sale of future royalties, net as of March 31, 2025
|
$
|
|
||
|
Less: Current portion (1)
|
(
|
)
|
||
|
Liability related to sale of future royalties, net as of March 31, 2025 – Non-current
|
$
|
|
| (1) |
Included in other current liabilities in our condensed consolidated balance sheet.
|
There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of royalty
payments from Biogen and Novartis, and result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to, the commercial sales of SPINRAZA, the regulatory approval and commercial sales of
pelacarsen, competing products or other significant events.
12. Convertible Debt
In 2023, we completed a $
575.0
million offering of our
1.75
% Notes. We used $
532.7
million of the net proceeds from the issuance of our
1.75
% Notes to repurchase and settle our
0.125
% Notes, which matured in December 2024.
At March 31, 2025, we had the following
1.75
% Notes outstanding (in millions except interest rate and price per share data):
|
|
||||
|
Outstanding principal balance
|
$
|
|
||
|
Unamortized debt issuance costs
|
$
|
|
||
|
Maturity date
|
|
|||
|
Interest rate
|
|
%
|
||
|
Effective interest rate
|
|
%
|
||
|
Conversion price per share
|
$
|
|
||
|
Total shares of common stock subject to conversion
|
|
|||
In 2021, we completed a $
632.5
million offering of our
0
% Notes. We used $
319.0
million of the net proceeds from the issuance of our
0
% Notes to pay the remaining $
309.9
million principal balance of our
1
percent convertible senior
notes, or
1
% Notes, in 2021.
At March 31, 2025, we had the following
0
%
Notes outstanding (in millions except interest rate and price
per share data):
|
|
||||
|
Outstanding principal balance
|
$
|
|
||
|
Unamortized debt issuance costs
|
$
|
|
||
|
Maturity date
|
|
|||
|
Interest rate
|
|
%
|
||
|
Effective interest rate
|
|
%
|
||
|
Conversion price per share
|
$
|
|
||
|
Effective conversion price per share with call spread
|
$
|
|
||
|
Total shares of common stock subject to conversion
|
|
|||
In conjunction with the 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and
selling warrants, to minimize the impact of potential economic dilution upon conversion of our
0
%
Notes by increasing the effective conversion price on our
0
%
Notes. We increased our effective conversion price to $
76.39
with the same number of underlying shares as our
0
%
Notes.
The call spread cost us $
46.9
million, of which $
136.7
million was for the note hedge purchase, offset by $
89.8
million we received for selling the warrants. Similar to our
0
%
Notes, our note hedges are subject to adjustment. Additionally, our note hedges
are exercisable upon conversion of the
0
%
Notes. The note
hedges will expire upon maturity of the
0
%
Notes, or April
2026. The warrants will expire in July 2026. The note hedges and warrants are separate transactions and are not part of the terms of our
0
%
Notes. The holders of the
0
%
Notes do not have any rights with respect to the note hedges and warrants.
We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our
condensed consolidated balance sheets. Refer to Part IV, Item 15, Note 1,
Organization and Significant Accounting Policies
, of our audited
financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 for our Call Spread accounting policy. We
reassess our ability to continue to classify the note hedges and warrants in shareholders’ equity at each reporting period.
Other Terms of Convertible Senior Notes
The
1.75
% and
0
% Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash,
shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of
certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to
100
percent of the principal
amount of the notes to be purchased, plus any accrued and unpaid interest.
13. Legal Proceedings
From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the
status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of
any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the
amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates.
There are no pending material legal proceedings to which we are a party or of which our property is the subject.
14. Segment Information
We operate as a
operating segment, Ionis operations, focused on the research, development and commercialization of our RNA-targeted medicines to bring better futures to people with serious diseases. As the CODM, our Chief Executive Officer manages our company, reviews
operating results, assesses performance and allocates resources on an aggregate basis using consolidated net income or loss as the key measure of segment profit or loss. As such, results of our operations are reported on a consolidated basis for
purposes of management and segment reporting.
Ionis operations derives its revenues from commercial and R&D revenue sources. Refer to Note 4,
Revenues
, for further details on our sources of revenue.
The following table sets forth information on segment profit or loss, including significant segment expenses (in thousands):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Revenue
|
$
|
|
$
|
|
||||
|
Less:
|
||||||||
|
Cost of sales
|
|
|
||||||
|
Drug discovery
|
|
|
||||||
|
Drug development
|
|
|
||||||
|
Medical affairs
|
|
|
||||||
|
Manufacturing and development chemistry
|
|
|
||||||
|
R&D support
|
|
|
||||||
|
Selling, general and administrative
|
|
|
||||||
|
Other segment items (1)
|
|
|
||||||
|
Consolidated net loss
|
$
|
(
|
)
|
$
|
(
|
)
|
||
| (1) |
|
| ITEM 2. |
MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS
|
In this Report on Form 10-Q, unless the context requires otherwise, “Ionis,” the “Company,” “we,” “our,” and “us,”
means Ionis Pharmaceuticals, Inc. and its subsidiaries.
Forward-Looking Statements
In addition to historical information contained in this Report on Form 10-Q, the Report includes forward-looking
statements regarding our business and the therapeutic and commercial potential of our commercial medicines, additional medicines in development and technologies. Any statement describing our goals, expectations, financial or other projections,
intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties and particularly those inherent in the process of discovering, developing and
commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Our forward-looking statements also involve assumptions that, if they never materialize or prove
correct, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those discussed in this report and
described in additional detail in our annual report on Form 10-K for the year ended December 31, 2024, which is on file with the U.S.
Securities and Exchange Commission and is available from us, and those identified within Part II Item 1A. Risk Factors of this Report. Although our forward-looking statements reflect the good faith judgment of our management, these statements are based
only on facts and factors currently known by us. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements.
For three decades, we have invented medicines that bring better futures to people with serious diseases. As a pioneer in RNA-targeted
medicines with a deep understanding of disease biology and an industry-leading drug discovery technology, we are driven to deliver innovative, life-changing advances for patients.
With our commercial launch of TRYNGOLZA (olezarsen) in the United States, or U.S., following its approval by the U.S. Food and Drug
Administration, or FDA, we began a new chapter as a fully integrated commercial-stage biotechnology company. We currently have six marketed medicines to treat serious diseases: TRYNGOLZA, WAINUA (eplontersen), SPINRAZA (nusinersen), QALSODY (tofersen),
TEGSEDI (inotersen) and WAYLIVRA (volanesorsen). In addition, we are also positioned to independently launch multiple medicines in the next two years, including donidalorsen for the treatment of hereditary angioedema, or HAE. Donidalorsen is currently
under regulatory review in the U.S., positioning us for our second independent commercial launch in the second half of this year. We are also on track for Phase 3 readouts later this year, which include olezarsen for severe hypertriglyceridemia, or
sHTG, and zilganersen for Alexander disease, or AxD. We also have a rich innovative pipeline across our focus areas of neurology, cardiology and select areas of high patient need. We currently have three wholly owned medicines and six partnered
medicines in Phase 3 development and additional medicines in early and mid-stage development, including ION528 for Angelman syndrome, or AS, which we plan to advance into a Phase 3 study in the second quarter of 2025.
Our multiple sources of revenue and capital structure enable our continued investments to support ongoing and upcoming planned launches
and to advance our wholly owned medicines in development. Our key recent achievements, combined with our independent and partnered product launches anticipated over the next three years, position us well to help millions of patients with serious
diseases and to deliver increasing product and royalty revenue.
Our Marketed Medicines
TRYNGOLZA is a once monthly, self-administered LIgand-Conjugated Antisense, or LICA, medicine approved in the U.S. as an adjunct to diet to reduce
triglycerides in adults with familial chylomicronemia syndrome, or FCS. TRYNGOLZA is the first and only FDA-approved treatment that significantly and substantially reduces triglyceride levels in adults with FCS and provides a clinically meaningful
reduction in acute pancreatitis, or AP, events. TRYNGOLZA is the first medicine we are commercializing independently in the U.S. TRYNGOLZA is currently under regulatory review in the European Union, or EU. Sobi has exclusive rights to commercialize
TRYNGOLZA in most countries outside of the U.S., Canada and China.
WAINUA (WAINZUA in Europe) is a once monthly, self-administered subcutaneous LICA medicine that is approved in the U.S., EU and other
countries for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis, or ATTRv-PN, a debilitating, progressive, and fatal disease. WAINUA is the only approved medicine for the treatment of ATTRv-PN that can be
self-administered via an auto-injector. The launch of WAINUA is underway in numerous countries, including the EU, following the approval by the European Commission, or EC, in March 2025. AstraZeneca has exclusive rights to commercialize WAINUA
outside of the U.S. From inception through March 31, 2025, we have earned more than $545 million in revenues from our WAINUA collaboration, including approximately $30 million in royalties on sales of WAINUA.
SPINRAZA is an antisense medicine for the treatment of
patients with spinal muscular atrophy, or SMA, a progressive, debilitating and often fatal genetic disease. Our partner, Biogen, is responsible for commercializing SPINRAZA worldwide
. From inception through March 31, 2025, we have earned more than $2.3
billion in revenues from our SPINRAZA collaboration, including more than $1.9 billion in royalties on sales of SPINRAZA.
QALSODY is an antisense medicine that received accelerated
approval from the FDA in April 2023 and marketing authorization under exceptional circumstances from the European Medicines Agency, or EMA, in May 2024 for the treatment of adult patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or
SOD1-ALS, a rare, neurodegenerative disorder that causes progressive loss of motor neurons leading to death. QALSODY was the first treatment approved to target a genetic cause of ALS. Our partner, Biogen, is responsible for commercializing QALSODY
worldwide.
Biogen is also evaluating QALSODY as a potential treatment for presymptomatic SOD1-ALS patients in the ongoing ATLAS study. QALSODY was granted Orphan Drug designation by the FDA and EMA.
TEGSEDI is a once weekly, self-administered subcutaneous medicine approved in Europe and Brazil for the treatment of patients with
ATTRv-PN. We currently sell TEGSEDI in Europe through our distribution agreement with Swedish Orphan Biovitrum AB, or Sobi. In Latin America, PTC Therapeutics International Limited, or PTC, is commercializing TEGSEDI in Brazil and is pursuing access in
additional Latin American countries through its exclusive license agreement with us.
WAYLIVRA is a once weekly, self-administered, subcutaneous medicine approved in Europe and Brazil as an adjunct to diet in adult
patients with genetically confirmed FCS and at high risk for pancreatitis. We sell WAYLIVRA in Europe through our distribution agreement with Sobi. In Latin America, PTC is commercializing WAYLIVRA in Brazil for two indications, FCS and familial
partial lipodystrophy, or FPL, and is pursuing access in additional Latin American countries through its exclusive license agreement with us.
Our Innovative Late-Stage Pipeline of Ionis-Owned Investigational Medicines
Olezarsen is our medicine in development for sHTG, a second potential indication which has a more prevalent patient population. We are
currently conducting a broad Phase 3 development program for olezarsen for the treatment of sHTG including three Phase 3 studies supporting development (CORE, CORE2 and ESSENCE), which achieved full enrollment in 2024. In March 2025, we published the
Phase 3 study design and baseline characteristics for the CORE, CORE2 and ESSENCE studies in the
American Heart Journal
.
We licensed commercialization rights for olezarsen to Sobi in most countries outside of the U.S., Canada and China, and Theratechnologies in Canada.
Donidalorsen is our medicine in development for the prophylactic treatment of HAE. Donidalorsen is currently under regulatory review in
the U.S. with a Prescription Drug User Fee Act, or PDUFA, action date of August 21, 2025. Donidalorsen is also under regulatory review in the EU. Our regulatory submissions are based on the positive results from our comprehensive Phase 2 and Phase 3
development program for donidalorsen. This included the Phase 3 OASIS-HAE study in patients treated every four weeks and every eight weeks that were published in
NEJM
, and positive results from OASISplus, our trial that includes an open-label, or OLE, cohort for patients rolling over from the Phase 3 study and a separate cohort for patients who have transitioned to donidalorsen from other
prophylactic HAE medications that we refer to as the “switch study.” We licensed commercialization rights for donidalorsen to Otsuka Pharmaceutical Co., Ltd., or Otsuka, in Europe and the Asia-Pacific region. In addition, we licensed
commercialization rights for donidalorsen to Theratechnologies in Canada. The FDA and EMA granted Orphan Drug designation to donidalorsen.
Zilganersen is our medicine in development for AxD. We completed enrollment in the Phase 3 portion of the ongoing study for patients with
AxD in July 2024. Zilganersen was granted Fast Track designation for the treatment of AxD and Rare Pediatric designation by the FDA. Additionally, zilganersen was granted Orphan Drug designation by the FDA and EMA.
ION582 is our medicine in development for AS. We are conducting the ongoing open label Phase 1/2 study, HALOS, of ION582 in patients with
AS designed to assess the safety, tolerability and activity of multiple ascending doses of ION582 administered intrathecally. In 2024, we presented positive results from the completed multiple ascending dose, or MAD, portion of the study in people with
AS. Based on the positive results from the HALOS study and alignment with the FDA, we plan to advance ION582 into Phase 3 development in the second quarter of 2025. The FDA and EMA granted Orphan Drug designation to ION582. Additionally, the FDA
granted Fast Track and Rare Pediatric designations to ION582.
Our Innovative Late-Stage Pipeline of Partnered Investigational Medicines
Eplontersen is our medicine in development to treat patients with transthyretin amyloidosis cardiomyopathy, or ATTR-CM. We completed
enrollment in the Phase 3 CARDIO-TTRansform study in July 2023. The FDA granted Fast Track designation to eplontersen for the treatment of patients with ATTR-CM. Additionally, the FDA and EMA granted Orphan Drug designation to eplontersen for the
treatment of ATTR.
Pelacarsen is our medicine in development to treat patients with elevated lipoprotein(a)-driven cardiovascular disease, or Lp(a)-driven
CVD. Novartis is developing pelacarsen, including conducting the ongoing Phase 3 Lp(a) HORIZON cardiovascular outcome study in patients with elevated Lp(a)-driven CVD, which achieved full enrollment in July 2022 with more than 8,000 patients. The study
design and baseline characteristics of the Phase 3 Lp(a) HORIZON study were published in the
American Heart Journal
in April 2025. The FDA granted
Fast Track designation and the Center for Drug Evaluation of China National Medical Products Administration granted Breakthrough Therapy designation to pelacarsen for the treatment of patients with elevated Lp(a) and established CVD.
Bepirovirsen is our medicine in development for chronic hepatitis B virus, or HBV. GSK is developing bepirovirsen, including conducting
the ongoing B-Well Phase 3 program in patients with HBV, which achieved full enrollment in June 2024. The FDA granted Fast Track designation and the Japanese Ministry of Health, Labour and Welfare granted SENKU designation to bepirovirsen for the
treatment of patients with HBV.
Sefaxersen is our medicine in development for immunoglobulin A, or IgA, nephropathy, or IgAN. In the second quarter of 2023, Roche
advanced sefaxersen into Phase 3 development in patients with IgAN based on interim Phase 2 data.
Ulefnersen is our medicine in development for amyotrophic lateral sclerosis, or ALS, with mutations in the fused in sarcoma gene, or FUS.
We are currently conducting a Phase 3 study of ulefnersen in juvenile and adult patients with FUS-ALS. We licensed global commercialization rights for ulefnersen to Otsuka. The FDA and EMA granted Orphan Drug designation to ulefnersen.
We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the U.S. As
such, we make certain estimates, judgments and assumptions that we believe are reasonable, based upon the information available to us. These judgments involve making estimates about the effect of matters that are inherently uncertain and may
significantly impact our quarterly or annual results of operations and financial condition. Each quarter, our senior management reviews the development, selection and disclosure of such estimates with the audit committee of our board of directors. The
following are our significant accounting estimates, which we believe are the most critical to aid in fully understanding and evaluating our reported financial results:
| ● |
Assessing the propriety of revenue recognition and associated deferred revenue;
|
| ● |
Determining the appropriate cost estimates for unbilled preclinical studies and clinical development activities; and
|
| ● |
Assessing the appropriate estimate of anticipated future royalty payments under our royalty purchase agreement
|
There have been no material changes to our critical accounting estimates from the information provided in Item 7,
Management’s Discussion and Analysis of Financial Condition and Results of Operations
, included in our Annual Report on Form 10-K for the year ended December 31, 2024.
The following is a summary of our financial results (in millions):
|
Three Months Ended
March 31
|
||||||||
|
2025
|
2024
|
|||||||
|
Total revenue
|
$
|
131.6
|
$
|
119.5
|
||||
|
Total operating expenses
|
$
|
278.5
|
$
|
269.0
|
||||
|
Loss from operations
|
$
|
(146.9
|
)
|
$
|
(149.5
|
)
|
||
|
Net loss
|
$
|
(146.9
|
)
|
$
|
(142.8
|
)
|
||
Revenue
Total revenue for the three months ended March 31, 2025 was $131.6 million compared to $119.5 million for the same period in 2024 and
was comprised of the following (in millions):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Revenue:
|
||||||||
|
Commercial revenue:
|
||||||||
|
Product sales, net:
|
||||||||
|
TRYNGOLZA sales, net
|
$
|
6.3
|
$
|
—
|
||||
|
Total product sales, net
|
6.3
|
—
|
||||||
|
Royalty revenue:
|
||||||||
|
SPINRAZA royalties
|
48.0
|
38.5
|
||||||
|
WAINUA royalties
|
9.4
|
1.1
|
||||||
|
Other royalties
|
6.8
|
9.8
|
||||||
|
Total royalty revenue
|
64.2
|
49.4
|
||||||
|
Other commercial revenue:
|
||||||||
|
TEGSEDI and WAYLIVRA revenue, net
|
5.7
|
8.6
|
||||||
|
Other revenue
|
—
|
1.6
|
||||||
|
Total other commercial revenue
|
5.7
|
10.2
|
||||||
|
Total commercial revenue
|
76.2
|
59.6
|
||||||
|
Research and development revenue:
|
||||||||
|
Collaborative agreement revenue
|
45.0
|
49.3
|
||||||
|
WAINUA joint development revenue
|
10.4
|
10.6
|
||||||
|
Total research and development revenue
|
55.4
|
59.9
|
||||||
|
Total revenue
|
$
|
131.6
|
$
|
119.5
|
||||
Commercial revenue for the three months ended March 31, 2025 increased 28% compared to the same period in 2024, driven in part by revenue
from U.S. product sales from the launch of TRYNGOLZA. Higher royalty revenues from SPINRAZA, WAINUA and QALSODY also contributed to the year over year increase.
The remainder of our revenue came from programs under our research and development, or R&D, collaborations, reflecting the value that
our pipeline and technology continue to generate.
WAINUA (Eplontersen) Collaboration with AstraZeneca
Our financial results for the three months ended March 31, 2025 and 2024 reflected the cost-sharing provisions related to our
collaboration with AstraZeneca to develop and commercialize WAINUA for the treatment of ATTR. Under the terms of the collaboration agreement, AstraZeneca is currently paying 55 percent of the costs associated with the ongoing global Phase 3 development
program. Because we are leading and conducting the Phase 3 development program, we are recognizing as R&D revenue the 55 percent of cost-share funding AstraZeneca is responsible for, net of our share of AstraZeneca's development expenses, in the
same period we incur the related development expenses.
As AstraZeneca is responsible for the majority of the medical affairs and commercial costs in the U.S. and all costs associated with
bringing WAINUA to market outside the U.S., we are recognizing cost-share funding we receive from AstraZeneca related to these activities as a reduction of our medical affairs and commercialization expenses, which we classify as R&D and selling,
general and administrative, or SG&A expenses, respectively. We expect our medical affairs and commercialization expenses to increase as WAINUA advances toward the market for ATTR-CM under our collaboration with AstraZeneca.
The following table sets forth information on revenue and expenses under this collaboration (in millions):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
WAINUA joint development revenue
|
$
|
10.4
|
$
|
10.6
|
||||
|
Research and development expenses related to Phase 3 development of WAINUA
|
21.5
|
22.7
|
||||||
|
Medical affairs expenses for WAINUA
|
1.6
|
1.3
|
||||||
|
Commercialization expenses for WAINUA
|
7.7
|
6.0
|
||||||
Operating Expenses
The following table sets forth information on operating expenses (in millions):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Operating expenses, excluding non-cash compensation expense related to equity awards
|
$
|
248.8
|
$
|
237.7
|
||||
|
Non-cash compensation expense related to equity awards
|
29.7
|
31.3
|
||||||
|
Total operating expenses
|
$
|
278.5
|
$
|
269.0
|
||||
Operating expenses, excluding non-cash compensation expense related to equity awards, for the three months ended March 31, 2025 increased slightly compared to the
same period in 2024. SG&A expenses increased year over year primarily due to the launches of WAINUA and TRYNGOLZA, and advancing launch
preparation activities for donidalorsen. R&D expenses decreased year over year as several late-stage studies ended. We expect our operating expenses, excluding non-cash compensation expense related to equity awards, to continue to increase during
the remainder of 2025 as we advance our commercialization activities.
To analyze and compare our results of operations to other similar companies, we believe it is important to exclude non-cash compensation
expense related to equity awards from our operating expenses. We believe non-cash compensation expense related to equity awards is not indicative of our operating results or cash flows from our operations. Further, we internally evaluate the
performance of our operations excluding it.
Cost of Sales
Our cost of sales is comprised of costs related to our commercial revenue, which consisted of manufacturing costs, including certain fixed
costs, transportation and freight, indirect overhead costs associated with the manufacturing and distribution of TRYNGOLZA, TEGSEDI and WAYLIVRA and certain associated period costs.
Cost of sales for a newly launched product, such as TRYNGOLZA, does not include the full cost of manufacturing until we manufacture and
sell additional inventory after exhausting pre-launch inventory, which we previously recorded as R&D expense.
The following table sets forth information on cost of sales (in millions):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Cost of sales, excluding non-cash compensation expense related to equity awards
|
$
|
1.4
|
$
|
2.0
|
||||
|
Non-cash compensation expense related to equity awards
|
0.1
|
0.2
|
||||||
|
Total cost of sales
|
$
|
1.5
|
$
|
2.2
|
||||
Research, Development and Patent Expenses
Our research, development and patent expenses consist of expenses for drug discovery, drug development, medical affairs, manufacturing and
development chemistry and R&D support expenses.
The following table sets forth information on research, development and patent expenses (in millions):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Research, development and patent expenses, excluding non-cash compensation expense related to equity awards
|
$
|
180.4
|
$
|
192.0
|
||||
|
Non-cash compensation expense related to equity awards
|
20.4
|
22.2
|
||||||
|
Total research, development and patent expenses
|
$
|
200.8
|
$
|
214.2
|
||||
Drug Discovery
We use our proprietary technologies to generate information about the function of genes and to determine the value of genes as drug
discovery targets. We use this information to direct our own drug discovery research, and that of our partners. Drug discovery is also the function that is responsible for advancing our core technology. This function is also responsible for making
investments in complementary technologies to expand the reach of our technologies.
The following table sets forth information on drug discovery expenses (in millions):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Drug discovery expenses, excluding non-cash compensation expense related to equity awards
|
$
|
27.0
|
$
|
28.2
|
||||
|
Non-cash compensation expense related to equity awards
|
4.1
|
4.3
|
||||||
|
Total drug discovery expenses
|
$
|
31.1
|
$
|
32.5
|
||||
Drug discovery expenses
, excluding non-cash
compensation expense related to equity awards,
were essentially flat in the
three months ended
March 31, 2025
compared to the same period in
2024
.
Drug Development
The following table sets forth drug development expenses, including expenses for our marketed medicines and those in Phase 3 development
for which we have incurred significant costs (in millions):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Eplontersen
|
$
|
21.1
|
$
|
21.7
|
||||
|
Olezarsen
|
24.9
|
39.5
|
||||||
|
Donidalorsen
|
5.1
|
4.8
|
||||||
|
Zilganersen
|
5.2
|
2.1
|
||||||
|
Ulefnersen
|
3.0
|
3.5
|
||||||
|
Other development projects
|
22.2
|
25.1
|
||||||
|
Development overhead expenses
|
31.4
|
29.1
|
||||||
|
Total drug development expenses, excluding non-cash compensation expense related to equity awards
|
112.9
|
125.8
|
||||||
|
Non-cash compensation expense related to equity awards
|
9.5
|
10.4
|
||||||
|
Total drug development expenses
|
$
|
122.4
|
$
|
136.2
|
||||
Our development expenses
, excluding non-cash
compensation expense related to equity awards,
decreased for the
three months ended
March 31, 2025
compared to the same period in
2024
as several late-stage studies ended
.
We expect our development expenses will continue to stabilize as
several late-stage studies end and we reallocate resources toward earlier stage programs.
We may conduct multiple clinical trials on a drug candidate, including multiple clinical trials for the various indications we may be
studying. Furthermore, as we obtain results from trials, we may elect to discontinue clinical trials for certain drug candidates in certain indications in order to focus our resources on more promising drug candidates or indications. Our Phase 1 and
Phase 2 programs are clinical research programs that fuel our Phase 3 pipeline. When our medicines are in Phase 1 or Phase 2 clinical trials, they are in a dynamic state in which we may adjust the development strategy for each medicine. Although we may
characterize a medicine as “in Phase 1” or “in Phase 2,” it does not mean that we are conducting a single, well-defined study with dedicated resources. Instead, we allocate our internal resources on a shared basis across numerous medicines based on
each medicine’s particular needs at that time. This means we are constantly shifting resources among medicines. Therefore, what we spend on each medicine during a particular period is usually a function of what is required to keep the medicines
progressing in clinical development, not what medicines we think are most important. For example, the number of people required to start a new study is large, the number of people required to keep a study going is modest and the number of people
required to finish a study is large. However, such fluctuations are not indicative of a shift in our emphasis from one medicine to another and cannot be used to accurately predict future costs for each medicine. Because we always have numerous
medicines in preclinical and varying stages of clinical research, the fluctuations in expenses from medicine to medicine, in large part, offset one another. If we partner a medicine, it may affect the size of a trial, its timing, its total cost and the
timing of the related costs.
Medical Affairs
Our medical affairs function is responsible for funding and coordinating investigator-sponsored trials, communicating scientific and
clinical information to healthcare providers, medical professionals and patients, and managing publications.
The following table sets forth information on medical affairs expenses (in millions):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Medical affairs expenses, excluding non-cash compensation expense related to equity awards
|
$
|
5.6
|
$
|
4.7
|
||||
|
Non-cash compensation expense related to equity awards
|
0.3
|
0.9
|
||||||
|
Total medical affairs expenses
|
$
|
5.9
|
$
|
5.6
|
||||
Medical affairs expenses
, excluding non-cash
compensation expense related to equity awards, increased in the three months ended March 31, 2025 compared to the same period in 2024 as we continued
advancing our late-stage pipeline.
Manufacturing and Development Chemistry
Expenditures in our manufacturing and development chemistry function consist primarily of personnel costs, specialized chemicals for
oligonucleotide manufacturing, validation batches to support regulatory approvals, laboratory supplies and outside services. Our manufacturing and development chemistry function is responsible for providing drug supplies to drug development and our
collaboration partners. Our manufacturing procedures include testing to satisfy good laboratory and good manufacturing practice requirements.
The following table sets forth information on manufacturing and development chemistry expenses (in millions):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Manufacturing and development chemistry expenses, excluding non-cash compensation expense related to equity awards
|
$
|
14.3
|
$
|
11.4
|
||||
|
Non-cash compensation expense related to equity awards
|
2.1
|
2.3
|
||||||
|
Total manufacturing and development chemistry expenses
|
$
|
16.4
|
$
|
13.7
|
||||
Manufacturing and development chemistry expenses, excluding
non-cash compensation expense related to equity awards, increased in
the three months ended March 31, 2025 compared to the same period in 2024 due to the timing
of manufacturing performed by our contract manufacturing organizations for drug product related to several late-stage programs.
R&D Support
In our research, development and patent expenses, we include support costs such as rent, repair and maintenance for buildings and
equipment, utilities, depreciation of laboratory equipment and facilities, amortization of our intellectual property, information technology costs, procurement costs and waste disposal costs. We call these costs R&D support expenses.
The following table sets forth information on R&D support expenses (in millions):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Occupancy
|
$
|
7.3
|
$
|
7.1
|
||||
|
Personnel costs
|
6.8
|
7.8
|
||||||
|
Computer software and licenses
|
3.2
|
1.6
|
||||||
|
Insurance
|
1.0
|
0.9
|
||||||
|
Patent expenses
|
0.6
|
0.7
|
||||||
|
Consulting expenses
|
0.1
|
0.6
|
||||||
|
Other
|
1.6
|
3.2
|
||||||
|
Total R&D support expenses, excluding non-cash compensation expense related to equity awards
|
20.6
|
21.9
|
||||||
|
Non-cash compensation expense related to equity awards
|
4.4
|
4.3
|
||||||
|
Total R&D support expenses
|
$
|
25.0
|
$
|
26.2
|
||||
R&D support expenses
, excluding non-cash
compensation expense related to equity awards,
were essentially flat in the
three months ended
March 31, 2025
compared to the same period in
2024
.
Selling, General and Administrative Expenses
SG&A expenses include personnel, information technology systems and outside costs associated with the commercialization and
pre-commercialization activities for our medicines and costs to support our company, our employees and our stockholders including, legal, human resources, investor relations and finance. Additionally, we include in SG&A expenses such costs as rent,
repair and maintenance of buildings and equipment, depreciation and utilities costs that we need to support the corporate functions listed above. We also include fees we owe under our in-licensing agreements related to SPINRAZA and QALSODY and cost
sharing payments associated with co-commercialization activities under our WAINUA collaboration with AstraZeneca.
The following table sets forth information on SG&A expenses (in millions):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Selling, general and administrative expenses, excluding non-cash compensation expense related to equity awards
|
$
|
67.0
|
$
|
43.7
|
||||
|
Non-cash compensation expense related to equity awards
|
9.3
|
8.9
|
||||||
|
Total selling, general and administrative expenses
|
$
|
76.3
|
$
|
52.6
|
||||
SG&A expenses
, excluding non-cash compensation
expense related to equity awards,
increased in the
three months ended
March 31, 2025
compared to the same period in
2024 due to the launches of WAINUA and TRYNGOLZA and advancing
launch preparation activities for donidalorsen. We expect SG&A expenses to increase as we continue to invest in our independent commercial launches.
Investment Income
Investment income for the three months ended March 31, 2025 was $24.7
million compared to $26.3 million for the same period in 2024. Our investment income decreased primarily due to a decrease in interest rates associated with our investments during the three months ended March 31, 2025 compared to the same period in 2024.
Interest Expense
The following table sets forth information on interest expense (in millions):
|
Three Months Ended
March 31,
|
||||||||
|
2025
|
2024
|
|||||||
|
Convertible notes:
|
||||||||
|
Non-cash amortization of debt issuance costs
|
$
|
1.5
|
$
|
1.6
|
||||
|
Interest expense payable in cash
|
2.5
|
2.5
|
||||||
|
Interest on mortgage for manufacturing facility
|
0.1
|
0.1
|
||||||
|
Total interest expense
|
$
|
4.1
|
$
|
4.2
|
||||
Interest Expense Related to Sale of Future Royalties
We recorded $
18.8
million and $
18.0
million of interest expense related to the sale of future royalties in the
three months ended
March 31, 2025
and 2024. respectively. These amounts are related to the Royalty Pharma Investments,
or Royalty Pharma, transaction, in which we sold a minority interest in our future SPINRAZA and pelacarsen royalties to Royalty Pharma for a $500 million upfront payment and $625 million of potential future payments. Refer to
Part I, Item 1,
Note 11,
Liability Related to Sale of Future Royalties
, in the Notes to Condensed Consolidated Financial Statements for further details.
Gain (Loss) on Investments
We recorded a net loss on investments of $2.2
million for the three months ended March 31, 2025 compared to a net gain on investments of $2.3 million for the same period in 2024 primarily due to changes in the fair value of our investments in publicly traded biotechnology companies.
Income Tax Expense
We recorded income tax expense of $0.1
million for the three months ended March 31, 2025 compared to $0.1 million for the same period in 2024.
We continue to maintain a full valuation allowance on all of our net deferred tax assets.
Net Loss and Net Loss per Share
We had a net loss of $146.9
million for the three months ended
March 31, 2025 compared to a net loss of $142.8
million for the same period in 2024, which reflects the fluctuations discussed above. Our b
asic and diluted net loss per share for the
three months ended
March 31, 2025
and
2024
was $
0.93
and $
0.98
, respectively.
We have financed our operations primarily from research and development collaborative agreements. We also financed our operations from
commercial revenue from SPINRAZA, WAINUA and QALSODY royalties and TEGSEDI and WAYLIVRA commercial revenue. In addition, we began earning commercial revenue from TRYNGOLZA product sales in late December 2024. From our inception through March 31, 2025, we have earned approximately $8.0
billion in revenue. We have also financed our operations through the sale of our equity securities, the issuance of long-term debt and the sale of future royalties. From the time we were founded through March 31, 2025, we have raised net proceeds of approximately $2.6
billion from the sale of our equity securities. Additionally, from our inception through March 31, 2025, we have borrowed approximately $2.7 billion under long-term debt arrangements and received proceeds of $0.5 billion from the sale of future royalties to finance a portion of our
operations.
From
December 31, 2024
to
March 31, 2025, our working capital decreased as our cash, cash equivalents and short-term investments decreased, while our long-term obligations did not change significantly.
The following table summarizes our contractual obligations, excluding our liability related to the sale of future royalties, as of March 31, 2025. The table provides a breakdown of when obligations become due. We provide a more detailed description of the major components of our debt
in the paragraphs following the table:
|
Contractual Obligations
|
Payments Due by Period (in millions)
|
|||||||||||
|
(selected balances described below)
|
Total
|
Less than
1 year
|
More than
1 year
|
|||||||||
|
1.75% Notes (principal and interest payable)
|
$
|
610.3
|
$
|
10.1
|
$
|
600.2
|
||||||
|
0% Notes (principal payable) (1)
|
632.5
|
—
|
632.5
|
|||||||||
|
Operating leases
|
255.0
|
20.9
|
234.1
|
|||||||||
|
Building mortgage payments (principal and interest payable)
|
9.5
|
0.5
|
9.0
|
|||||||||
|
Other obligations (principal and interest payable)
|
0.7
|
0.1
|
0.6
|
|||||||||
|
Total
|
$
|
1,508.0
|
$
|
31.6
|
$
|
1,476.4
|
||||||
(1) Our 0% Notes become due in April 2026.
Our contractual obligations consist primarily of our convertible debt. In addition, we also have a facility mortgage, facility leases,
equipment financing arrangements and other obligations. We believe our cash, cash equivalents and short-term investments, as well as plans for cash in the future, will be sufficient to fund our planned operations and these obligations. We have not
entered into, nor do we currently have, any off-balance sheet arrangements (as defined under SEC rules).
Convertible Debt and Call Spread
Refer to Part I, Item 1, Note 12,
Convertible
Debt
, in the Notes to Condensed Consolidated Financial Statements for the significant terms of each convertible debt instrument.
Operating Facilities
Refer to Part IV, Item 15, Note 7 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 for further details on our operating facilities.
Operating Leases
Refer to Part IV, Item 15, Note 7 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 for further details on our operating leases.
Liability Related to Sale of Future Royalties
Refer to Part I, Item 1,
Note 11,
Liability Related to Sale of Future Royalties,
in the Notes to Condensed Consolidated Financial Statements for further details on our royalty purchase
agreement with Royalty Pharma.
Other Obligations
In addition to contractual obligations, we had outstanding purchase orders as of March 31, 2025 for the purchase of services, capital equipment and materials as part of our normal course of business.
We may enter into additional collaborations with partners which could provide for additional revenue to us and we may incur additional
cash expenditures related to our obligations under any of the new agreements we may enter into. We currently intend to use our cash, cash equivalents and short-term investments to finance our activities. However, we may also pursue other financing
alternatives, like issuing additional shares of our common stock, issuing debt instruments, refinancing our existing debt, securing lines of credit or executing royalty monetization agreements. Whether we use our existing capital resources or choose to
obtain financing will depend on various factors, including the future success of our business, the prevailing interest rate environment and the condition of financial markets generally.
| ITEM 3. |
QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK
|
We are exposed to changes in interest rates primarily from our investments in certain short-term investments. We primarily invest our
excess cash in highly liquid short-term investments of the U.S. Treasury and reputable financial institutions, corporations, and U.S. government agencies with strong credit ratings. We typically hold our investments for the duration of the term of the
respective instrument. We do not utilize derivative financial instruments, derivative commodity instruments or other market risk sensitive instruments, positions or transactions to manage exposure to interest rate changes. Accordingly, we believe that,
while the securities we hold are subject to changes in the financial standing of the issuer of such securities, we are not subject to any material risks arising from changes in interest rates, foreign currency exchange rates, commodity prices, equity
prices or other market changes that affect market risk sensitive instruments.
We are also exposed to changes in foreign currency exchange rates as we have foreign subsidiaries with functional currencies other than
the U.S. dollar. We translate our subsidiaries’ functional currencies into our reporting currency, the U.S. dollar. As a result, our financial position, results of operations and cash flows can be affected by market fluctuations in the foreign
currencies to U.S. dollar exchange rate, which are difficult to predict. A hypothetical 10 percent change in foreign exchange rates during any of the periods presented would not have had a material impact on our condensed consolidated financial
statements.
| ITEM 4. |
CONTROLS AND PROCEDURES
|
We maintain disclosure controls and procedures that are designed to ensure that information we are required to disclose in our Exchange
Act reports is recorded, processed, summarized and reported within the time periods specified in the SEC’s rules and forms, and that such information is accumulated and communicated to our management, including our Chief Executive Officer and Chief
Financial Officer, as appropriate, to allow timely decisions regarding required disclosure. We design and evaluate our disclosure controls and procedures recognizing that any controls and procedures, no matter how well designed and operated, can
provide only reasonable assurance and not absolute assurance of achieving the desired control objectives.
As of our most recently completed fiscal year and as of the end of the period covered by this Quarterly Report on Form 10-Q, we carried
out an evaluation of the effectiveness of the design and operation of our disclosure controls and procedures, as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended, under the supervision and with the
participation of our management, including our Chief Executive Officer and Chief Financial Officer. Based on our evaluation, our Chief Executive Officer and Chief Financial Officer concluded that our disclosure controls and procedures were effective as
of March 31, 2025.
There have been no significant changes in our
internal controls or in other factors that could significantly affect internal controls subsequent to
March 31, 2025.
We also performed an evaluation of any changes in our internal controls over financial reporting that occurred during our last fiscal
quarter and that have materially affected, or are reasonably likely to materially affect, our internal controls over financial reporting. We conducted this evaluation under the supervision of and with the participation of our management, including our
Chief Executive Officer and Chief Financial Officer. That evaluation did not identify any changes in our internal controls over financial reporting that occurred during our latest fiscal quarter and that have materially affected, or are reasonably
likely to materially affect, our internal controls over financial reporting.
| ITEM 1. |
LEGAL PROCEEDINGS
|
For details of legal proceedings, refer to Part I, Item 1, Note 13,
Legal Proceedings
, in the Notes to Condensed Consolidated Financial Statements
.
| ITEM 1A. |
RISK FACTORS
|
Investing in our securities involves a high degree of risk. You should carefully consider the following information
about the risks described below, together with the other information contained in this report and in our other public filings in evaluating our business. If any of the following risks actually occur, our business could be materially harmed, and our
financial condition and results of operations could be materially and adversely affected. As a result, the trading price of our securities could decline, and you might lose all or part of your investment. We have marked with an asterisk those risk
factors that reflect substantive changes from the risk factors included in our Annual Report on Form 10-K for the year ended December 31, 2024.
Summary of Risk Factors
There are a number of risks related to our business and our securities. Some of the principal risks related to our business include the
following:
| ● |
Our ability to generate substantial revenue from the sale of our medicines;
|
| ● |
Τ
he availability of adequate coverage and payment rates for our medicines;
|
| ● |
Our and our partners’ ability to compete effectively;
|
| ● |
Our ability to successfully manufacture our medicines;
|
| ● |
Our ability to successfully develop and obtain marketing approvals for our medicines;
|
| ● |
Our ability to secure and maintain effective corporate partnerships;
|
| ● |
Our ability to sustain cash flows and achieve consistent profitability;
|
| ● |
Our ability to protect our intellectual property;
|
| ● |
Our ability to maintain the effectiveness of our personnel;
|
| ● |
The impacts of health epidemics, climate change, war and other events;
|
| ● |
Our dependence upon our own and third-party information technology systems; and
|
| ● |
The other factors set forth below.
|
Risks Related to the Commercialization of our Medicines
We have limited experience as a company in commercializing medicines and we will have to continue to invest significant resources to
develop our capabilities. If we are unable to effectively establish or maintain an effective commercialization infrastructure, or enter into agreements with third parties to commercialize our medicines, we may not be able to successfully commercialize
our medicines.
We have historically relied on third parties to commercialize our marketed medicines and have limited experience as a company in
commercializing medicines. TRYNGOLZA is our first independently launched medicine and we expect to independently launch additional medicines in the future. Any failure to effectively commercialize our medicines, including our failure to allocate
resources to our commercial launches efficiently or timely, could adversely impact the revenue we generate from our medicines. If the commercialization of TRYNGOLZA and future sales are less successful than anticipated by us or our investors or
securities analysts, our stock price could decline and our business may be harmed.
We will have to continue to invest significant financial and management resources to build and maintain the infrastructure required to
successfully commercialize our medicines. We will need to establish and maintain effective sales teams for each of our independently launched medicines and there are significant risks involved in managing a sales organization, including our ability to
hire, retain and incentivize qualified individuals, generate sufficient sales leads, provide adequate training to sales and marketing personnel, and effectively manage a geographically dispersed sales and marketing team. We must also continue to
scale-up existing internal support functions to aid our commercialization efforts. Further, these existing support functions will need to work effectively in coordination with new commercial functional areas. Any failure to establish or maintain an
effective commercialization infrastructure, including our sales, marketing, market access, distribution, and related capabilities, scale-up our existing support functions, or effectively integrate new functional areas, could adversely affect our
ability to successfully commercialize our medicines.
If we choose to rely on third parties to assist us in commercializing our medicines, we may not be able to enter into collaborations or
hire consultants or external service providers on acceptable financial terms, or at all. In addition, if we continue to engage third parties to assist us in the commercialization of our medicines, our product revenues and profitability may be lower
than if we commercialized such medicines ourselves.
The proximity of our planned upcoming independent launches could increase the likelihood that the risks set forth above will occur.
If the market does not accept our medicines, including our commercial medicines and our medicines in development, we are not likely to
generate substantial revenues or become consistently profitable.
Even if our medicines are authorized for marketing, our success will depend upon the medical community, patients and third-party payers
accepting our medicines as medically useful, cost-effective, safe and convenient. Even when the FDA or foreign regulatory authorities authorize our or our partners’ medicines for commercialization, doctors may not prescribe our medicines to treat
patients. Furthermore, we and our partners may not successfully commercialize additional medicines.
Additionally, in many of the markets where we or our partners may sell our medicines in the future, if we or our partners cannot agree
with the government or other third-party payers regarding the price we can charge for our medicines, we may not be able to sell our medicines in that market. Similarly, cost control initiatives by governments or third-party payers could decrease the
price received for our medicines or increase patient coinsurance to a level that makes our medicines, including our commercial medicines and our medicines in development, economically unviable. If the pricing of any of our medicines decreases for any
reason, it will reduce our revenue for such medicine. For example, Biogen has in the past disclosed that SPINRAZA revenue decreased in part due to lower pricing in the U.S. and certain rest-of-world markets.
The degree of market acceptance for our medicines, including our commercial medicines and our medicines in development, depends upon
several factors, including the:
| ● |
receipt and scope of marketing authorizations;
|
| ● |
establishment and demonstration in the medical and patient community of the efficacy and safety of our medicines, public perception regarding our medicines and their
potential advantages over competing products;
|
| ● |
cost and effectiveness of our medicines compared to other available therapies;
|
| ● |
patient convenience of the dosing regimen for our medicines; and
|
| ● |
reimbursement policies of government and third-party payers.
|
Based on the profile of our medicines, physicians, patients, patient advocates, payers or the medical community in general may not accept or use any of the
medicines that we or our partners may develop. For example, the product label for WAYLIVRA in the EU requires regular blood monitoring, which has negatively affected our ability to attract and retain patients for this medicine.
If government or other third-party payers fail to provide adequate coverage and payment rates for our medicines, including our commercial
medicines and our medicines in development, our revenue will be limited.
In both domestic and foreign markets, sales of our current and future products will depend in part upon the availability of coverage and
reimbursement from third-party payers. The majority of patients in the U.S. who would fit within our target patient populations for our medicines have their healthcare supported by a combination of Medicare coverage, other government health programs
such as Medicaid, managed care providers, private health insurers and other organizations. Coverage decisions may depend upon clinical and economic standards that disfavor new medicines when more established or lower cost therapeutic alternatives are
already available or subsequently become available. Assuming coverage is approved, the resulting reimbursement payment rates might not be enough to make our medicines affordable. Even if favorable coverage status and adequate reimbursement rates are
attained, less favorable coverage policies and reimbursement rates may be implemented in the future. Accordingly, our commercial medicines and our medicines in development will face competition from other therapies and medicines for limited financial
resources. Furthermore, we or our partners may need to conduct post-marketing studies to demonstrate the cost-effectiveness of any future products to satisfy third-party payers. These studies might require us to commit a significant amount of
management time and financial and other resources. In addition, third-party payers may never consider our future products as cost-effective and adequate third-party coverage and reimbursement might not be available to enable us to maintain price levels
sufficient to realize an appropriate return on investment in product development.
Third-party payers, whether foreign or domestic, or governmental or commercial, are developing increasingly sophisticated methods of
controlling healthcare costs. In addition, in the U.S., no uniform policy of coverage and reimbursement for medicines exists among third-party payers. Therefore, coverage and reimbursement for medicines can differ significantly from payer to payer. For
example, the Affordable Care Act, or ACA, was passed in March 2010, and substantially changed the way healthcare is financed by both governmental and private insurers and continues to significantly impact the U.S. pharmaceutical industry. There have
been judicial and Congressional challenges to certain aspects of the ACA, as well as efforts to repeal or replace certain aspects of the ACA. It is unclear how future litigation and healthcare reform measures will impact the ACA and our business.
Further, we believe that future coverage, reimbursement and pricing will likely be subject to increased restrictions both in the U.S. and
in international markets. In the U.S., recent health reform measures have resulted in reductions in Medicare and other healthcare funding, and there have been several recent U.S. Congressional inquiries, legislation and executive orders designed to,
among other things, reduce drug prices, increase competition (including by enhancing support for generic and biosimilar drugs), lower out-of-pocket drug costs for patients, curtail spread pricing practices by pharmacy benefit managers, and foster
scientific innovation to promote better health care and improved health. In addition, the Inflation Reduction Act of 2022, or the IRA, includes key actions aimed at reducing the costs of prescription drugs and allows HHS to negotiate the price of
certain single-source drugs covered under Medicare and establish a price cap on such drugs. The IRA, among other things, (1) directs HHS to negotiate the price of certain single-source drugs and biologics that have been on the market for at least seven
years covered under Medicare, or the Medicare Drug Price Negotiation Program, and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation. These provisions began to take effect progressively
starting in fiscal year 2023, although the Medicare Drug Price Negotiation Program is currently subject to legal challenges. Under this program, HHS has already announced the agreed-upon prices of the first drugs that were subject to price negotiations
and will announce the agreed-upon prices of additional drugs in the coming years. In response to an October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the CMS Innovation Center that will
be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care. It is unclear whether the models will be utilized in any health reform measures in the future. Further, on December 7, 2023, the Biden
administration announced an initiative to control the price of prescription drugs using march-in rights under the Bayh-Dole Act. On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance
Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights. While march-in rights have not previously been exercised, it
is uncertain if that will continue under the new framework. It is unclear whether or how these selected models or similar policy initiatives will impact prescription drug pricing in the future, particularly in light of the recent U.S. presidential and
congressional elections.
Any reduction in reimbursement from Medicare and other government programs may result in a similar reduction in payments from private
payers. Our future product sales may be subject to additional discounts from list price in the form of rebates and discounts provided to covered entities under the Public Health Service Act 340B drug pricing program. Changes to the 340B program or to
Medicare or Medicaid programs at the federal or state level, including outcomes of ongoing litigation in our industry, may impact our product prices and rebate liability.
At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and
biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from
other countries and bulk purchasing. For example, on January 5, 2024, the FDA approved Florida’s Section 804 Importation Program, or SIP, proposal to import certain drugs from Canada for specific state healthcare programs. It is unclear how this
program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the United States or Canada. Other states have also submitted SIP proposals that are pending review by the FDA. Any such approved
importation plans, when implemented, may result in lower drug prices for products covered by those programs. Third-party coverage and reimbursement for medicines may not be available or adequate in either the U.S. or international markets, which would
negatively affect the potential commercial success of our products, our revenue and our profits.
If we or our partners fail to compete effectively, our medicines, including our commercial medicines and our medicines in development,
will not generate significant revenues.
Our competitors engage in drug discovery throughout the world, are numerous, and include, among others, major pharmaceutical companies and
specialized biopharmaceutical firms. In addition, other companies are engaged in developing RNA-targeted technology. Our competitors may succeed in developing medicines that are:
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priced lower than our medicines;
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reimbursed more favorably by government and other third-party payers than our medicines;
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safer than our medicines;
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more effective than our medicines; or
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more convenient to use than our medicines.
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These competitive developments could make our medicines, including our commercial medicines and our medicines in development, obsolete or
non-competitive.
Certain of our partners are pursuing other technologies or developing other medicines either on their own or in collaboration with others,
including our competitors, to treat some of the same diseases that our own programs target. Competition may negatively impact a partner’s focus on and commitment to our medicines and, as a result, could delay or otherwise negatively affect the
commercialization of our medicines, including our commercial medicines and our medicines in development.
Many of our competitors have substantially greater financial, technical and human resources than we do. In addition, many of these
competitors have significantly greater experience than we do in conducting preclinical testing and human clinical studies of new pharmaceutical products, in obtaining FDA and other regulatory authorizations of such products and in commercializing such
products. Accordingly, our competitors may succeed in obtaining regulatory authorization for products earlier than we do or more successfully commercialize their products.
There are several pharmaceutical and biotechnology companies engaged in the development or commercialization in certain geographic markets
of products against targets that are also targets of products in our development pipeline or of medicines we are commercializing. For example:
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Onasemnogene abeparvovec and risdiplam compete with SPINRAZA;
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Acoramidis, patisiran, tafamidis, tafamidis meglumine and vutrisiran compete with WAINUA;
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Nexiguran ziclumeran, ALXN2220 and NNC6019-0001 could compete with WAINUA;
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Plozasiran, pegozafermin and NST-1024 could compete with TRYNGOLZA and WAYLIVRA;
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Lanadelumab-flyo, C1 esterase inhibitor, berotralstat, C1 esterase inhibitor subcutaneous,
garadacimab,
deucrictibant,
NTLA-2002 and STAR-0215 could compete with donidalorsen;
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Olpasiran,
zerlasiran, lepodisiran and muvalaplin
could compete with pelacarsen;
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NI-005/AP-101 could compete with QALSODY;
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VIR-2218, VIR-3434, BRII-179, AB-729, selgantolimod,
bersacapavir, REP 2139-Mg and VTP-300 could complete with bepirovirsen;
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Budesonide, sparsentan, atrasentan, iptacopan, zigakibart, sibeprenlimab, atacicept, ravulizumab, vemircopan, felzartamab, telitacicept and povetacicept could compete
with sefaxersen; and
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GTX-102, alogabat and NNZ-2591 could compete with ION582.
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SPINRAZA injection for intrathecal use is an antisense medicine indicated for the treatment of SMA patients of all ages approved in over
50 countries. Specifically, SPINRAZA faces competition from onasemnogene abeparvovec, a gene therapy product that was approved in the U.S. in May 2019 and in the EU in May 2020 for the treatment of SMA, as well as risdiplam, an oral product for the
treatment of SMA that was approved in the U.S. in August 2020 and in the EU in March 2021. Biogen has in the past disclosed that SPINRAZA revenue decreased due to a reduction in demand as a result of increased competition and that future sales of
SPINRAZA may be adversely affected by competing products.
Additionally, companies that are developing medicines that
target the same patient populations as our medicines in development may compete with us to enroll participants in the clinical trials for such medicines, which could make it more difficult for us to complete enrollment for these clinical trials
.
Our medicines could be subject to regulatory limitations following approval.
Following approval of a medicine, we and our partners must comply with comprehensive government regulations regarding the manufacture,
marketing and distribution of medicines. The FDA and foreign regulatory bodies have the authority to impose significant restrictions on an approved medicine through the product label. We or our partners may not obtain the labeling claims necessary or
desirable to successfully commercialize our medicines, including our commercial medicines and our medicines in development.
Promotional communications regarding prescription medicines must be consistent with the information in the product’s approved labeling.
Additionally, prescription medicines may be promoted only for the approved indication(s) in accordance with the approved label. The FDA and other regulatory authorities actively enforce the laws and regulations prohibiting the promotion of off-label
uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.
In addition, when approved, the FDA or a foreign regulatory authority may condition approval on the performance of post-approval clinical
studies or patient monitoring, which could be time consuming and expensive. For example, in connection with the conditional marketing approval for WAYLIVRA in the EU, we are required to conduct a post-authorization safety study to evaluate the safety
of WAYLIVRA on thrombocytopenia and bleeding in FCS patients taking WAYLIVRA. If the results of such post-marketing studies are not satisfactory, the FDA, EC or other foreign regulatory authorities may withdraw the marketing authorization or may
condition continued marketing on commitments from us or our partners that may be expensive and time consuming to fulfill.
If we or others identify side effects after any of our medicines are on the market, or if manufacturing problems occur subsequent to
regulatory approval, or if we, our CMOs or our partners fail to comply with regulatory requirements, we or our partners may, among other things, lose regulatory approval and be forced to withdraw products from the market, need to conduct additional
clinical studies, incur restrictions on the marketing, distribution or manufacturing of the product, and/or change the labeling of our medicines.
We depend on our collaborations with Biogen for the development and commercialization of SPINRAZA and QALSODY.
We have entered into separate collaborative arrangements with Biogen to develop and commercialize SPINRAZA and QALSODY. We entered into
these collaborations primarily to:
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fund our development activities for SPINRAZA and QALSODY;
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seek and obtain regulatory approvals for SPINRAZA and QALSODY; and
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successfully commercialize SPINRAZA and QALSODY.
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We are relying on Biogen to obtain additional regulatory approvals for SPINRAZA and QALSODY, generate additional clinical data for
SPINRAZA and QALSODY, manufacture SPINRAZA and QALSODY, and successfully commercialize SPINRAZA and QALSODY. In general, we cannot control the amount and timing of resources that Biogen devotes to our collaborations. If Biogen fails to further develop
SPINRAZA or QALSODY, obtain additional regulatory approvals for SPINRAZA or QALSODY, manufacture SPINRAZA or QALSODY, or successfully commercialize SPINRAZA or QALSODY, or if Biogen’s efforts in any of these respects are ineffective, revenues for
SPINRAZA or QALSODY would be negatively affected.
In addition, our collaborations with Biogen may not continue for various reasons. Biogen can terminate our collaborations at any time. If
Biogen stops developing or commercializing SPINRAZA or QALSODY, we would have to seek or spend additional funding, and SPINRAZA’s or QALSODY’s commercialization may be harmed.
We depend on our collaboration with AstraZeneca for the joint development and commercialization of WAINUA.
We have entered into a collaborative arrangement with AstraZeneca to develop and commercialize WAINUA. Under the terms of the
collaboration agreement, we and AstraZeneca are co-developing and co-commercializing WAINUA in the U.S. and AstraZeneca has the sole right to commercialize WAINUA in all other countries. As a company we do not have experience with co-commercialization
arrangements. We also do not have control over (1) the amount and timing of resources that AstraZeneca devotes to our collaboration, particularly outside of the U.S; (2) the pricing and reimbursement strategies for WAINUA; and (3) whether AstraZeneca
elects to terminate the collaborative arrangement. If the co-commercialization arrangement for WAINUA is not successful for any reason, WAINUA may not meet our commercial objectives and our revenues for WAINUA may be limited.
In addition, a Joint Steering Committee, or JSC, having equal membership from us and AstraZeneca, and various subcommittees oversee and
coordinate the development, manufacturing, commercialization and other exploitation activities for WAINUA in the U.S. by mutual agreement. If any subcommittee cannot reach unanimous agreement on any matter within its respective scope of authority, such
matter may be referred to the JSC for resolution. If the JSC cannot come to a mutual agreement on any particular matter, this could delay our ability to develop or commercialize WAINUA.
If we are not successful in expanding our manufacturing capabilities or cannot manufacture our medicines or contract with a third party to
manufacture our medicines at costs that allow us to charge competitive prices to buyers, we cannot market our products profitably.*
To successfully commercialize any of our medicines, we need
to optimize and manage large-scale commercial manufacturing capabilities either on a standalone basis or through a third-party manufacturer. As our drug development and commercial pipeline increases and matures, we will have a greater need for
clinical trial and commercial manufacturing capacity. We will also need to ensure that we have the manufacturing capabilities in place to support advances in our drug development activities, such as new chemistries. While
we believe
our current capabilities and those we obtain through third-party manufacturers support our manufacturing needs now, it will be important to expand our manufacturing infrastructure
in the future, which will likely require substantial expenditures. If we are not successful in executing this expansion, it could limit our ability to meet our manufacturing requirements and commercial objectives in the future.
In addition, we have limited experience manufacturing pharmaceutical products of the chemical class represented by our medicines, called
oligonucleotides, on a commercial scale for the systemic administration of a medicine. There are a small number of suppliers for certain capital equipment and raw materials that we use to manufacture our medicines, and some of these suppliers will need
to increase their scale of production to meet our projected needs for commercial manufacturing. If a supplier chooses to devote more resources to other products, especially products with higher manufacturing capacity needs, that could impact such
supplier’s capability to deliver our requirements timely. Further, we must continue to improve our manufacturing processes to allow us to reduce our drug costs. We or our partners may not be able to manufacture our medicines at a cost or in quantities
necessary to make commercially successful products.
Manufacturers, including us, must adhere to the FDA’s cGMP regulations and similar regulations in foreign countries, which the applicable
regulatory authorities enforce through facilities inspection programs. We, our partners and our contract manufacturers may not comply or maintain compliance with cGMP, or similar foreign regulations. Non-compliance could significantly delay or prevent
receipt of marketing authorizations for our medicines, including authorizations for our commercial medicines and our medicines in development, or could result in enforcement action after authorization that might limit the commercial success of our
medicines.
We rely on third-party manufacturers to supply the drug
substance and drug product for TRYNGOLZA and WAINUA and drug product for WAYLIVRA. The operations of our suppliers, many of which are located outside of the United States, are subject to additional risks that are beyond our control. For example,
tariffs on the raw materials, components, or equipment we use to manufacture our products, or on our drug substance or finished products, will increase our manufacturing costs. There have also been Congressional legislative proposals, such as the
recent bill titled the BIOSECURE Act, to discourage contracting with Chinese companies for the development or manufacturing of pharmaceutical products. In addition, merger and acquisition activity within the commercial manufacturing space could
reduce the availability of resources from our third-party manufacturers. Delays or disruption to our own or third-party commercial manufacturing capabilities for any reason could limit the commercial success of our medicines
.
Risks Related to the Development and Regulatory Approval of our Medicines
If we or our partners fail to obtain regulatory approval for our medicines and additional approvals for our commercial medicines, we or
our partners cannot sell them in the applicable markets.
We cannot guarantee that any of our medicines will be considered safe and effective or will be approved for commercialization. In
addition, it is possible that our commercial medicines may not be approved in additional markets or for additional indications. We and our partners must conduct time-consuming, extensive and costly clinical studies to demonstrate the safety and
efficacy of each of our medicines before they can be approved or receive additional approvals for sale. We and our partners must conduct these studies in compliance with FDA regulations and with comparable regulations in other countries.
We and our partners may not obtain necessary regulatory approvals on a timely basis, if at all, for our medicines. It is possible that
regulatory authorities will not approve our medicines for marketing or our commercial medicines in additional markets or for additional indications. If the FDA or another regulatory authority believes that we or our partners have not sufficiently
demonstrated the safety or efficacy of any of our medicines, including our commercial medicines or our medicines in development, the authority will not approve the specific medicine or will require additional studies, which could be time consuming and
expensive and delay or harm commercialization of the medicine. For example, in August 2018 we received a complete response letter from the FDA regarding the new drug application for WAYLIVRA in which the FDA determined that the safety concerns
identified with WAYLIVRA in our clinical development program outweighed the expected benefits of triglyceride lowering in patients with FCS. We also received a Notice of Non-Compliance Withdrawal Letter, or Non-W, from Health Canada for WAYLIVRA in
November 2018.
The FDA or other comparable foreign regulatory authorities can delay, limit or deny approval of a medicine for many reasons, including:
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such authorities may disagree with the design or implementation of our clinical studies;
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we or our partners may be unable to demonstrate to the satisfaction of the FDA or other regulatory authorities that a medicine is safe and effective for any indication;
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such authorities may not accept clinical data from studies conducted at clinical facilities that have deficient clinical practices or that are in countries where the
standard of care is potentially different from the U.S.;
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we or our partners may be unable to demonstrate that our medicine’s clinical and other benefits outweigh its safety risks to support approval;
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such authorities may disagree with the interpretation of data from preclinical or clinical studies;
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such authorities may find deficiencies in the manufacturing processes or facilities of third-party manufacturers who manufacture clinical and commercial supplies for our
medicines; and
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the approval policies or regulations of such authorities or their prior guidance to us or our partners during clinical development may significantly change in a manner
rendering our clinical data insufficient for approval.
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Failure to receive marketing authorization for our medicines in development, or failure to receive additional marketing authorizations for
our commercial medicines, or delays in these authorizations, could prevent or delay commercial introduction of the medicine, and, as a result, could negatively impact our ability to generate revenue from product sales.
If the results of clinical testing indicate that any of our medicines are not suitable for commercial use, we may need to abandon one or
more of our drug development programs.
Drug discovery and drug development have inherent risks and the historical failure rate for drugs is high. Antisense medicines are a
relatively new approach to therapeutics. If we cannot demonstrate that our medicines are safe and effective for human use in the intended indication(s), we may need to abandon one or more of our drug development programs.
Even if our medicines are successful in preclinical and human clinical studies, the medicines may not be successful in late-stage clinical
studies. Similarly, topline, preliminary or interim data we release for any of our clinical studies may not be indicative of full or final results from such study.
Successful results in preclinical or initial human clinical studies, including the Phase 2 results for some of our medicines in
development, may not predict the results of subsequent clinical studies. If any of our medicines in Phase 3 clinical studies do not show sufficient safety and efficacy in patients with the targeted indication, or if such studies are discontinued for
any other reason, it could negatively impact our development and commercialization goals for these medicines and our stock price could decline. In addition, we may release topline, preliminary or interim data for any of our clinical studies. The
interim, topline or preliminary results we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. As a result, such
data should be viewed with caution until the final data are available.
In the past, we have invested in clinical studies of medicines that have not met the primary clinical endpoints in their Phase 3 studies
or have been discontinued for other reasons. For example, in October 2021, Biogen reported that QALSODY did not meet the primary clinical endpoint in the Phase 3 VALOR study; however, trends favoring QALSODY were seen across multiple secondary and
exploratory measures of disease activity and clinical function. In addition, in March 2021, Roche decided to discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest Huntington’s disease based on the results of a
pre-planned review of data from the Phase 3 study conducted by an unblinded Independent Data Monitoring Committee. Similar results could occur in clinical studies for our other medicines.
There are a number of factors that could cause a clinical study to fail or be delayed, including:
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the clinical study may produce negative or inconclusive results;
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regulators may require that we hold, suspend or terminate clinical research for noncompliance with regulatory requirements;
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we, our partners, the FDA or foreign regulatory authorities could suspend or terminate a clinical study due to adverse side effects of a medicine on subjects or lack of
efficacy in the trial;
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we or our partners may decide, or regulators may require us, to conduct additional preclinical testing or clinical studies;
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enrollment in our clinical studies may be slower than we anticipate;
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we or our partners, including our independent clinical investigators, contract research organizations and other third-party service providers on which we rely, may not
identify, recruit or train suitable clinical investigators at a sufficient number of study sites or timely enroll a sufficient number of study subjects in the clinical study;
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the institutional review board for a prospective site might withhold or delay its approval for the study;
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people who enroll in the clinical study may later drop out due to adverse events, a perception they are not benefiting from participating in the study, fatigue with the
clinical study process or personal issues;
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a clinical study site may deviate from the protocol for the study;
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the cost of our clinical studies may be greater than we anticipate;
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our partners may decide not to exercise any existing options to license and conduct additional clinical studies for our medicines; and
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the supply or quality of our medicines or other materials necessary to conduct our clinical studies may be insufficient, inadequate or delayed.
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Further, the FDA or other regulatory authorities could request, among other things, additional information or commitments before we can
start or continue a clinical study, protocol amendments, increased safety monitoring, additional product labeling information, and post-approval commitments. This happened in connection with the conditional marketing approval for WAYLIVRA in the EU, as
the European Commission is requiring us to conduct a post-authorization safety study to evaluate the safety of WAYLIVRA on thrombocytopenia and bleeding in FCS patients taking WAYLIVRA. In addition, under accelerated approval the FDA is requiring
completion of the ongoing Phase 3 trial for QALSODY to confirm the clinical benefit of QALSODY.
Moreover, our commercial medicines are chemically similar to each other. As a result, a safety observation we encounter with one of our
medicines could have, or be perceived by a regulatory authority to have, an impact on a different medicine we are developing. This could cause the FDA or other regulators to ask questions or take actions that could harm or delay our ability to develop
and commercialize our medicines or increase our costs. Any failure or delay in our clinical studies could reduce the commercial potential or viability of our medicines.
We depend on third parties to conduct clinical studies for our medicines and any failure of those parties to fulfill their obligations
could adversely affect our development and commercialization plans.
We depend on independent clinical investigators, contract research organizations and other third-party service providers to conduct our
clinical studies for our medicines and expect to continue to do so in the future. For example, we use clinical research organizations, such as Icon Clinical Research Limited, Medpace, Inc., Parexel International Corporation, Syneos Health, Inc. and
Thermo Fisher Scientific Inc. for the clinical studies for our medicines, including WAINUA for the treatment of ATTR-CM, donidalorsen, olezarsen, ulefnersen and zilganersen. We rely heavily on these parties for successful execution of our clinical
studies, but do not control many aspects of their activities. For example, the investigators are not our employees, but we are responsible for ensuring that such investigators conduct each of our clinical studies in accordance with the general
investigational plan and approved protocols for the study. Third parties may not complete activities on schedule or may not conduct our clinical studies in accordance with regulatory requirements or our stated protocols. For example, some of our key
vendors have in the past experienced labor shortages, which impacted their ability to perform services for us for certain of our clinical trials. Subsequent failures of these third parties to carry out their obligations, or a termination of our
relationship with such third parties, could delay or prevent the development, marketing authorization and commercialization of our medicines.
In addition, while we do not have any clinical trial sites in Russia, Ukraine or Gaza, we do have a limited number of clinical trial sites
in Israel that may be materially impacted by the ongoing military conflicts in Israel and elsewhere in the Middle East and could result in difficulties enrolling or completing our clinical trials in such areas on schedule.
Since corporate partnering is part of our strategy to fund the advancement and commercialization of some of our development programs, if
any of our collaborative partners fail to fund our collaborative programs, or if we cannot obtain additional partners, we may have to delay or stop progress on those drug development programs.
To date, corporate partnering has played a significant role in our strategy to fund our development programs and to add key development
resources. While we are now commercializing some of our medicines independently, we still plan to continue to rely on additional collaborative arrangements to develop and commercialize some of our unpartnered medicines. However, we may not be able to
negotiate favorable collaborative arrangements for these drug programs. If we cannot continue to secure additional collaborative partners, our revenues could decrease and the development of our medicines could suffer.
Our corporate partners are developing and funding many of the medicines in our development pipeline. For example, we are relying on:
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AstraZeneca for the joint development and funding of WAINUA;
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Novartis for development and funding of pelacarsen;
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GSK for development and funding of bepirovirsen; and
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Roche for development and funding of sefaxersen.
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If any of these pharmaceutical companies stops developing and funding these medicines, our business could suffer and we may not have, or
be willing to dedicate, the resources available to develop these medicines on our own. Our collaborators can terminate their relationships with us under certain circumstances, many of which are outside of our control. For example, in 2022, Pfizer and
Bayer decided to discontinue the clinical development programs for vupanorsen and fesomersen, respectively.
Even with funding from corporate partners, if our partners do not effectively perform their obligations under our agreements with them, it
would delay or stop the progress of our drug development and commercial programs.
In addition to receiving funding, we enter into collaborative arrangements with third parties to:
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conduct clinical studies;
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seek and obtain marketing authorizations; and
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manufacture and commercialize our medicines.
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Once we have secured a collaborative arrangement to further develop and commercialize one of our drug development programs, such as our
collaborations with AstraZeneca, Biogen, GSK, Novartis, Otsuka and Roche, these collaborations may not continue or result in commercialized medicines, or may not progress as quickly as we anticipated.
For example, a collaborator such as AstraZeneca, Biogen, GSK, Novartis, Otsuka or Roche, could determine that it is in its financial
interest to:
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pursue alternative technologies or develop alternative products that may be competitive with the medicine that is part of the collaboration with us;
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pursue higher-priority programs or change the focus of its own development programs; or
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choose to devote fewer resources to our medicines than it does to its own medicines.
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If any of these occur, it could affect our partner’s commitment to the collaboration with us and could delay or otherwise negatively
affect the commercialization of our medicines, including QALSODY, SPINRAZA, WAINUA, bepirovirsen, donidalorsen, sefaxersen and pelacarsen.
We may not be able to benefit from designations for our medicines from regulatory authorities that are intended to confer benefits such as
financial incentives or an accelerated regulatory pathway.
In the U.S., under the Orphan Drug Act, the FDA may designate a medicine as an Orphan Drug if it is intended to treat a rare disease or
condition affecting fewer than 200,000 individuals in the U.S. Orphan Drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process, but it can provide financial incentives, such as tax
advantages and user-fee waivers, as well as longer regulatory exclusivity periods. The FDA has granted Orphan Drug designation to TRYNGOLZA for the treatment of patients with FCS, to WAINUA for the treatment of patients with ATTR, to ulefnersen for the
treatment of patients with FUS-ALS, to ION582 for the treatment of patients with Angelman syndrome, and to some of our earlier stage medicines. The FDA and EMA have granted Orphan Drug designation to donidalorsen for the treatment of patients with HAE,
to WAYLIVRA for the treatment of patients with FCS, to tominersen for the treatment of patients with HD, and to some of our earlier stage medicines. In addition, the EMA has granted Orphan Drug designation to WAYLIVRA for the treatment of patients with
FPL. Even if approval is obtained on a medicine that has been designated as an Orphan Drug, we may lose Orphan Drug exclusivity if the FDA or EMA determines that the request for designation was materially defective or if we cannot assure sufficient
quantity of the applicable medicine to meet the needs of patients with the rare disease or condition, or if a competitor is able to gain approval for the same or a substantially similar medicine in a safer or more effective form or that makes a major
contribution to patient care. If we lose Orphan Drug exclusivity on any of our medicines, we may face increased competition and lose market share for such medicine.
We may also seek rare pediatric disease designation for some of our medicines. The FDA defines “rare pediatric disease” as a serious or
life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years or is a rare disease or condition within the meaning of the Orphan Drug Act. Designation of a medicine as a
medicine for a rare pediatric disease does not guarantee that a marketing application for such medicine will meet the eligibility criteria for a rare pediatric disease priority review voucher, or PRV, at the time the application is approved. Under the
FDCA, we will need to request a rare pediatric disease PRV in our original marketing application for any potential medicine for which we have received rare pediatric disease designation. The FDA may determine that a marketing application for any such
medicine, if approved, does not meet the eligibility criteria for a PRV. Under the current statutory sunset provisions, after December 20, 2024, the FDA may only award a PRV for an approved rare pediatric disease application if the sponsor has rare
pediatric disease designation for the drug or biologic that is the subject of such application, and that designation was granted by December 20, 2024. After September 30, 2026, the FDA may not award any rare pediatric disease PRVs. However, it is
possible the authority for FDA to award rare pediatric disease PRV will be further extended by Congress.
Risks Associated with our Businesses as a Whole
Risks related to our financial condition
If we fail to obtain timely funding, we may need to curtail or abandon some of our programs.
Many of our medicines are undergoing clinical studies or are in the early stages of research and development. Most of our programs will
require significant additional research, development, manufacturing, preclinical and clinical testing, marketing authorizations, preclinical activities and commitment of significant additional resources prior to their successful commercialization. In
addition, as we commercialize more medicines on our own, we will need to invest significant financial resources to continue developing the infrastructure required to successfully commercialize our medicines, including building and maintaining new
support functions and scaling up existing internal support functions and expanding our manufacturing capabilities. All of these activities will require significant cash. As of March 31, 2025, we had cash, cash equivalents and short-term investments equal to $2.1
billion. If we or our partners do not meet our goals to successfully commercialize our medicines, including our commercial medicines, or to license certain medicines and proprietary technologies, we will need additional funding in the future. Our
future capital requirements will depend on many factors such as:
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successful commercialization of our commercial medicines;
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the profile and launch timing of our medicines in development;
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changes in existing collaborative relationships and our ability to establish and maintain additional collaborative arrangements;
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continued scientific progress in our research, drug discovery and development programs;
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the size of our programs and progress with preclinical and clinical studies;
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the time and costs involved in obtaining marketing authorizations;
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competing technological and market developments, including the introduction by others of new therapies that address our markets; and
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our manufacturing requirements and capacity to fulfill such requirements.
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If we need additional funds, we may need to raise them through public or private financing. Additional financing may not be available on
acceptable terms or at all. If we raise additional funds by issuing equity securities, the shares of existing stockholders will be diluted and the price, as well as the price of our other securities, may decline. For example, in September 2024, we
completed an underwritten public offering of 11,500,000 shares of our common stock for total net proceeds, after deducting underwriting discounts and commissions and other offering expenses payable by us, of approximately $489.1 million. If adequate
funds are not available or not available on acceptable terms, we may have to cut back on one or more of our research, drug discovery or development programs, or commercial operations. Alternatively, we may obtain funds through arrangements with
collaborative partners or others, which could require us to give up rights to certain of our technologies or medicines.
We have incurred losses, and our business will suffer if we fail to consistently achieve profitability in the future.
Because drug discovery and development require substantial lead-time and money prior to commercialization, our expenses have generally
exceeded our revenue since we were founded in January 1989. As of March 31, 2025, we had an accumulated deficit of approximately $2.4 billion and stockholders’ equity of approximately $0.5
billion. Most of our income has historically come from collaborative arrangements, including commercial revenue from royalties and R&D revenue, with additional income from research grants and the sale or licensing of our patents, as well as
interest income. We will now and continuing into the foreseeable future need to invest significant financial resources to commercialize medicines on our own and expect that our income in the future will be driven primarily by commercial sales. If we do
not earn substantial revenue from commercial sales, we may incur additional operating losses in the future, which could restrict our ability to successfully develop additional medicines or sustain future profitability.
We may not be entitled to obtain additional milestone payments under our royalty monetization agreement with Royalty Pharma.
In January 2023, we entered into a Royalty Purchase Agreement with Royalty Pharma Investments. In addition to the $500 million we received
at closing, this agreement makes available to us up to an additional $625 million in milestone payments. However, these additional milestone payments are subject to satisfaction of certain conditions related to the regulatory approval or commercial
sales of pelacarsen, in certain cases by specific deadlines. Should we not satisfy such conditions by the applicable deadlines, or if we fail to meet our obligations or default under this agreement, the actual amount of additional payments to us could
be substantially less than the maximum amounts available thereunder.
Risks related to our intellectual property
If we cannot protect our patent rights or our other proprietary rights, others may compete more effectively against us.
Our success depends to a significant degree upon whether we can continue to develop, secure and maintain intellectual property rights to
proprietary products and services. However, we may not receive issued patents on any of our pending patent applications in the U.S. or in other countries and we may not be able to obtain, maintain or enforce our patents and other intellectual property
rights, any of which could impact our ability to compete effectively. In addition, the scope of any of our issued patents may not be sufficiently broad to provide us with a competitive advantage. Furthermore, other parties may successfully challenge,
invalidate or circumvent our issued patents or patents licensed to us so that our patent rights do not create an effective competitive barrier or revenue source.
We cannot be certain that the U.S. Patent and Trademark Office, or U.S. PTO, and courts in the U.S. or the patent offices and courts in
foreign countries will consider the claims in our patents and applications covering our commercial medicines, or any of our medicines in development, as patentable. Method-of-use patents protect the use of a product for the specified method. This type
of patent does not prevent a competitor from making and marketing a product that is identical to our product for an indication that is outside the scope of the patented method. Moreover, even if competitors do not actively promote their product for our
targeted indications, physicians may prescribe these products off-label. Although off-label prescriptions may infringe or contribute to the infringement of method-of-use patents, the practice is common and such infringement is difficult to prevent,
even through legal action.
If we or any licensor partner loses or cannot obtain patent protection for our commercial medicines or any of our medicines in
development, it could have a material adverse impact on our business.
Intellectual property litigation could be expensive and prevent us from pursuing our programs.
From time to time, we have to defend our intellectual property rights. If we are involved in an intellectual property dispute, we may need
to litigate to defend our rights or assert them against others. Disputes can involve arbitration, litigation or proceedings declared by the U.S. PTO or the International Trade Commission or foreign patent authorities. Even if resolved in our favor,
litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public
announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.
If a third party claims that our medicines or technology infringe its patents or other intellectual property rights, we may have to
discontinue an important product or product line, alter our products and processes, pay license fees or cease certain activities. We may not be able to obtain a license to needed intellectual property on favorable terms, if at all. There are many
patents issued or applied for in the biotechnology industry, and we may not be aware of patents or patent applications held by others that relate to our business. This is especially true since patent applications in the U.S. are filed confidentially
for the first 18 months. Moreover, the validity and breadth of biotechnology patents involve complex legal and factual questions for which important legal issues remain.
Risks related to product liability
We are exposed to potential product liability claims, and insurance against these claims may not be available to us at a reasonable rate
in the future or at all.
Our business exposes us to potential product liability risks that are inherent in the testing, manufacturing, marketing and sale of
therapeutic products, including potential product liability claims related to our commercial medicines and our medicines in development. We have clinical study insurance coverage and commercial product liability insurance coverage. However, this
insurance coverage may not be adequate to cover claims against us, or be available to us at an acceptable cost, if at all. Regardless of their merit or eventual outcome, product liability claims may result in decreased demand for our medicines, injury
to our reputation, withdrawal of clinical study volunteers and loss of revenues. Thus, whether or not we are insured, a product liability claim or product recall may result in losses that could be material.
Risks related to our personnel
The loss of key personnel, or the inability to attract and retain highly skilled personnel, could make it more difficult to run our
business and reduce our likelihood of success.
We are dependent on the principal members of our management,
scientific and commercial staff. We do not have employment agreements with any of our employees that would prevent them from leaving us. The loss of our key management, scientific or commercial employees might slow the achievement of important
research and development or commercial goals. It is also critical to our success that we recruit and retain qualified scientific personnel to perform research and development work and that we recruit and retain qualified marketing, sales, market
access, distribution, and related personnel to commercialize our medicines. We may not be able to attract and retain skilled and experienced personnel on acceptable terms because of intense competition for experienced personnel among many
pharmaceutical and health care companies, universities and non-profit research institutions. In addition, failure to succeed in clinical studies or in commercializing our medicines may make it more challenging to recruit and retain qualified
personnel
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Risks related to health epidemics, climate change and other events
Our business may be adversely affected by health epidemics, climate change, extreme weather events, fires, earthquakes, war, civil or
political unrest, terrorism or disruptions of the U.S. government.*
Our business could be adversely affected by health epidemics in regions where we or our partners are commercializing our medicines, have
concentrations of clinical trial sites or other business operations, and could cause disruption in the operations of third-party manufacturers and contract research organizations upon whom we rely. For example, enrollment in some of our clinical trials
was delayed due to the COVID-19 pandemic.
In recent years, extreme weather events and changing weather patterns have become more common. As a result, we are potentially exposed to
varying natural disaster or extreme weather risks such as fires, hurricanes, tornadoes, droughts, floods, or other events that may result from the impact of climate change on the environment, any of which could impact our business and manufacturing
operations. The potential impacts of climate change may also include increased operating costs associated with additional regulatory requirements and investments in reducing energy, water use and greenhouse gas emissions. In addition, we currently
manufacture most of our research and clinical supplies in a manufacturing facility located in Carlsbad, California, and various regions within California have recently experienced numerous catastrophic wildfires. We manufacture the finished drug
product for TRYNGOLZA, WAYLIVRA and eplontersen for ongoing clinical trials at third-party contract manufacturers. Biogen manufactures the finished drug product for SPINRAZA and QALSODY and AstraZeneca is responsible for WAINUA’s commercial drug
supply. The facilities and the equipment we, our partners and our contract manufacturers use to research, develop and manufacture our medicines would be costly to replace and could require substantial lead time to repair or replace.
Our facilities or those of our partners or contract manufacturers may be harmed by natural disasters or other events outside our control,
such as earthquakes, war, civil or political unrest, deliberate acts of sabotage, terrorism or industrial accidents such as fire and explosion, whether due to human or equipment error, and if such facilities are affected by a disaster or other event,
our development and commercialization efforts would be delayed. Although we possess property damage and business interruption insurance coverage, this insurance may not be sufficient to cover all of our potential losses and may not continue to be
available to us on acceptable terms, or at all.
In addition, our development and commercialization activities could be harmed or delayed by staffing shortages or a shutdown or other
significant disruption of the U.S. government, including the FDA or the U.S. PTO.
Risks related to personal information, cybersecurity, social media and artificial intelligence
We are dependent on data as well as information technology systems and infrastructure, which exposes us to data protection risks.
We are dependent upon our own and third-party data as well as information technology systems and infrastructure, including mobile
technologies, to operate our business. The personal information we process subjects us to stringent and evolving U.S. and foreign laws, rules and regulations, contractual obligations, industry standards and other obligations related to data privacy and
security. Our personal information obligations require us to implement and maintain certain practices, including those in relation to cross-border transfers of personal information. The multitude and complexity of our information technology systems and
infrastructure make them vulnerable to a variety of evolving threats that may result in systems or data interruption, corruption, destruction, disruption of data integrity, malicious intrusion, or random attacks or other compromise (such as due to
malfunctions, software vulnerabilities, natural disasters, telecommunications failures, malicious actors and personnel error). Data privacy or security incidents or breaches pose a risk that sensitive data, including our intellectual property, trade
secrets or personal information of our employees, patients, customers or other business partners may be exposed to unauthorized persons. Cyber-attacks are increasing in their frequency, sophistication and intensity, particularly as companies (including
us) continue to move to more remote work structures. In addition, the number and frequency of cybersecurity events globally may be heightened during times of geopolitical tension or instability between countries, including, for example, the ongoing war
between Russia and Ukraine and military conflicts in the Middle East and the surrounding areas, or collectively, conflicts in Eastern Europe and the Middle East, as well as related political or economic responses and counter-responses by various global
actors.
Cybersecurity related events could include the deployment or use of harmful malware or malicious code, denial-of-service attacks,
credential stuffing attacks, credential harvesting attacks, social engineering attacks (including deep fakes), ransomware and other means to affect the confidentiality, integrity or availability of our data as well as information systems and
infrastructure. Our current, past and prospective business partners face similar risks and any security breaches of their systems could adversely affect our security posture. A security breach or privacy violation (including perceived breaches or
violations) could result in any of the following, any of which could disrupt our business and result in increased costs or loss of revenue:
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harm our reputation;
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delay progress on the development of our medicines;
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compel us to comply with applicable security or data breach notification obligations (including laws);
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result in the diversion of monetary funds and other company resources;
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subject us to financial or other penalties, regulatory investigations or actions, including mandatory and costly corrective actions; and
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require us to verify the correctness of database contents and otherwise subject us to litigation or other liabilities.
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Risk mitigation strategies such as liability limitations in our contracts and insurance coverage may prove inadequate if there is a
security breach or privacy violation. While we have invested, and continue to invest, in the protection of our data and information technology systems and infrastructure, our efforts may not be successful. Non-compliance with relevant data protection
obligations or a failure to secure our data, information technology systems or infrastructure could adversely affect our business and operations and result in the loss of critical or sensitive information, which could result in financial, legal,
business or reputational harm to us.
The increasing use of social media platforms and artificial intelligence based software presents new risks and challenges.
Social media is increasingly being used to communicate about our medicines and the diseases our therapies are designed to treat. Social
media practices in the biopharmaceutical industry continue to evolve and regulations relating to such use are not always clear and create uncertainty and risk of noncompliance with regulations applicable to our business. There is also a risk of
inappropriate disclosure of sensitive information or negative or inaccurate posts or comments about us on social media. We may also encounter criticism on social media regarding our company, management, or medicines. Our reputation could be damaged by
negative publicity or if adverse information concerning us is posted on social media platforms or similar mediums, which we may not be able to reverse. If any of these events were to occur or we otherwise fail to comply with applicable regulations, we
could incur liability, face restrictive regulatory actions or incur other harm to our business.
Additionally, artificial intelligence, or AI, based software is increasingly being used in the biopharmaceutical industry. Use of AI based
software may lead to the release of confidential proprietary information, which may impact our ability to realize the benefit of our intellectual property.
Risks related to our securities and the global credit markets
If we do not progress in our programs as anticipated, the price of our securities could decrease.
For planning purposes, we estimate and may disclose the timing of a variety of clinical, regulatory and other milestones, such as when we
anticipate a certain medicine will enter clinical trials, when we anticipate disclosing clinical data, when we anticipate completing a clinical study, when we anticipate filing an application for, or obtaining, marketing authorization, or when we or
our partners plan to commercially launch a medicine. We base our estimates on present facts and a variety of assumptions, many of which are outside of our control. If we do not achieve milestones in accordance with our or our investors’ or securities
analysts’ expectations, including milestones related to our commercial medicines and medicines in development, the price of our securities could decrease. In addition, our share price may be dependent upon the valuations and recommendations of the
analysts who cover our business. If our results do not meet these analysts’ forecasts, the expectations of our investors or the financial guidance we provide to investors in any period, the market price of our common stock could decline. Our ability to
meet analysts’ forecasts, investors’ expectations and our financial guidance is substantially dependent on our ability to maintain or increase sales of our commercial medicines, both partnered and unpartnered.
If the price of our securities continues to be highly volatile, this could make it harder to liquidate your investment and could increase
your risk of suffering a loss.*
The market price of our common stock, like that of the securities of many other biopharmaceutical companies, has been and is likely to
continue to be highly volatile. These fluctuations in our common stock price may significantly affect the trading price of our securities. During the 12 months preceding March 31, 2025, the closing market price of our common stock ranged from $51.86 to $30.17 per share. Many factors can affect the market price of our securities, including, for example, fluctuations in our operating results, financing
transactions, announcements of collaborations, clinical study results, technological innovations or new products being developed by us or our competitors, the commercial success of our approved medicines, governmental regulation, marketing
authorizations, changes in payers’ reimbursement policies, developments in patent or other proprietary rights and public concern regarding the safety of our medicines.
Broad market factors may materially harm the market price of our common stock irrespective of our operating performance. For example,
events such as recent tariffs announcements and the ongoing conflicts in Eastern Europe and the Middle East have caused disruptions of global financial markets and resulted in increased volatility in the trading price of our common stock. In addition,
industry factors may materially harm the market price of our common stock. Nasdaq, and the market for biotechnology companies in particular, have historically experienced extreme price and volume fluctuations that have often been unrelated or
disproportionate to the operating performance of the particular companies affected. The trading prices and valuations of these stocks, and of ours, may not be predictable. A loss of investor confidence in the market for biotechnology or pharmaceutical
stocks or the stocks of other companies that investors perceive to be similar to us, the opportunities in the biotechnology and pharmaceutical market or the stock market in general, could depress our stock price regardless of our business, prospects,
financial conditions or results of operations.
Negative conditions in the global credit markets and financial services and other industries may adversely affect our business, financial
condition or stock price.*
The global credit and financial markets have experienced extreme volatility and disruptions recently, including as a result of tariffs
announcements and the ongoing conflicts in Eastern Europe and the Middle East. These disruptions can result in severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in
unemployment rates and uncertainty about economic stability. There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur. If the current equity and credit markets
deteriorate, it may make any necessary debt or equity financing more difficult, more costly and more dilutive. Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect on our operations,
growth plans, financial performance or stock price. In addition, our insurance carriers and insurance policies covering all aspects of our business may become financially unstable or may not be sufficient to cover any or all of our losses and may not
continue to be available to us on acceptable terms, or at all.
A variety of risks associated with operating our business and
marketing our medicines internationally could adversely affect our business. In addition to our U.S. operations, we are commercializing WAYLIVRA in the EU, Latin America and certain Caribbean countries. We face risks associated with our international
operations, including possible unfavorable regulatory, pricing and reimbursement, political, tax and labor conditions, which could harm our business. Because we have international operations, we are subject to numerous risks associated with
international business activities, including
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compliance with differing or unexpected regulatory requirements for our medicines and foreign employees;
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complexities associated with managing multiple payer reimbursement regimes, government payers or patient self-pay systems;
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difficulties in staffing and managing foreign operations;
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in certain circumstances, increased dependence on the commercialization efforts and regulatory compliance of third-party distributors or strategic partners;
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foreign government taxes, regulations and permit requirements;
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U.S. and foreign government tariffs, trade and export restrictions, price and exchange controls and other regulatory requirements;
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anti-corruption laws, including the Foreign Corrupt Practices Act, or the FCPA, and its equivalent in foreign jurisdictions;
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economic weakness, including inflation, natural disasters, war, acts of terrorism, political instability or public health issues or health epidemics, in particular
foreign countries or globally;
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fluctuations in currency exchange rates, which could result in increased operating expenses and reduced revenue, and other obligations related to doing business in
another country;
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the potential for a local seller, faced with higher local prices, importing medicines from an international market with lower prices rather than buying such medicines
locally, which is referred to as parallel importation;
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compliance with tax, employment, privacy, immigration and labor laws, regulations and restrictions for employees living or traveling abroad;
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workforce uncertainty in countries where labor unrest is more common than in the U.S.; and
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changes in diplomatic and trade relationships.
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Our business activities outside of the U.S. are subject to the FCPA and similar anti-bribery or anti-corruption laws, regulations or rules
of other countries in which we operate, including the United Kingdom’s Bribery Act 2010. In many other countries, the healthcare providers who prescribe pharmaceuticals are employed by their government, and the purchasers of pharmaceuticals are
government entities; therefore, any dealings with these prescribers and purchasers may be subject to regulation under the FCPA. There is no certainty that all employees and third-party business partners (including our contract research organizations,
contract manufacturing organizations, distributors, wholesalers, agents, contractors and other partners) will comply with anti-bribery laws. Importantly, we do not control the actions of manufacturers and other third-party agents, although we may be
liable for their actions. Violation of these laws may result in civil or criminal sanctions, which could include monetary fines, criminal penalties, and disgorgement of past profits, which could have an adverse impact on our business and financial
condition.
Provisions in our certificate of incorporation, bylaws, convertible notes documents, call spread hedge transaction documents and Delaware
law may prevent stockholders from receiving a premium for their shares.
Our certificate of incorporation provides for classified terms for the members of our board of directors. Our certificate also includes a
provision that requires at least 66 2/3 percent of our voting stockholders to approve a merger or certain other business transactions with, or proposed by, any holder of 15 percent or more of our voting stock, except in cases where certain directors
approve the transaction or certain minimum price criteria and other procedural requirements are met.
Our certificate of incorporation also requires that any action required or permitted to be taken by our stockholders must be taken at a
duly called annual or special meeting of stockholders and may not be taken by written consent. In addition, only our board of directors, chairperson of the board or chief executive officer can call special meetings of our stockholders. We have in the
past, and may in the future, implement a stockholders’ rights plan, also called a poison pill, which could make it uneconomical for a third party to acquire our company on a hostile basis. In addition, our board of directors has the authority to fix
the rights and preferences of, and issue shares of preferred stock, which may have the effect of delaying or preventing a change in control of our company without action by our stockholders.
The provisions of our convertible senior notes could make it more difficult or more expensive for a third party to acquire us. Upon the
occurrence of certain transactions constituting a fundamental change, holders of the notes will have the right, at their option, to require us to repurchase all of their notes or a portion of their notes, which may discourage certain types of
transactions in which our stockholders might otherwise receive a premium for their shares over the then-current market prices.
In 2023, we completed a $575 million offering of 1.75% Notes and used $488.2 million of the net proceeds from the issuance of the 1.75%
Notes to repurchase $504.4 million of our 0.125% Notes. In 2024, we used $44.5 million of the net proceeds to settle the remaining principal balance of our 0.125% Notes upon maturity. In 2021, we completed a $632.5 million offering of 0% Notes and used
$319.0 million of the net proceeds from the issuance of the 0% Notes to repurchase the remaining $309.9 million of our 1% Notes. In 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and
certain holders of our existing 1% Notes to exchange $375.6 million of our 1% Notes for $439.3 million of our 0.125% Notes, and to issue $109.5 million of our 0.125% Notes. Additionally, in connection with the pricing of our 0% Notes and 0.125% Notes,
we entered into call spread transactions in which we purchased note hedges and sold warrants. For our 0.125% Notes, the note hedges expired upon maturity of the 0.125% Notes and the warrants began expiring in March 2025. Terminating or unwinding the
call spread transactions for our 0% Notes could require us to make substantial payments to the counterparties under those agreements or may increase our stock price. The costs or any increase in stock price that may arise from terminating or unwinding
such agreements could make an acquisition of our company significantly more expensive to the purchaser.
These provisions, as well as Delaware law, including Section 203 of the Delaware General Corporation Law, and other of our agreements, may
discourage certain types of transactions in which our stockholders might otherwise receive a premium for their shares over then-current market prices, and may limit the ability of our stockholders to approve transactions that they think may be in their
best interests.
Future sales of our common stock in the public market could adversely affect the trading price of our securities.
Future sales of substantial amounts of our common stock in
the public market, or the perception that such sales could occur, could adversely affect trading prices of our securities. For example, we may issue approximately 21.6 million shares of our common stock upon conversion of our 1.75% Notes and 0%
Notes. In connection with the issuance of the 0% Notes, we entered into certain call spread transactions covering 10.9 million shares
that we expect will
offset the
dilution to holders of common stock upon any conversion
of those notes.
However, the anti-dilutive effect of the convertible note hedges is offset by certain
warrant transactions we entered into in connection with the issuance of the 0% Notes. The addition of any of these shares into the public market may have an adverse effect on the price of our securities.
In addition, pursuant to the call spread transactions we entered into in connection with the pricing of our 0% Notes, the counterparties
are likely to modify their hedge positions from time to time at or prior to the conversion or maturity of the notes by purchasing and selling shares of our common stock, other of our securities, or other instruments, including over-the-counter
derivative instruments, that they may wish to use in connection with such hedging, which may have a negative effect on the conversion value of those notes and an adverse impact on the trading price of our common stock. The call spread transactions are
expected generally to reduce potential dilution to holders of our common stock upon any conversion of our 0% Notes or offset any cash payments we are required to make in excess of the principal amount of the converted 0% Notes, as the case may be.
However, the warrant transactions could separately have a dilutive effect to the extent that the market value per share of our common stock exceeds the applicable strike price of the warrants.
Risks related to compliance with laws
Our operations are subject to extensive legal and regulatory requirements affecting the health care industry.
Our operations are subject to extensive legal and regulatory requirements affecting the health care industry, including federal and state
anti-kickback laws, false claims laws, transparency laws, such as the federal Sunshine Act, and health information privacy and security laws, which are subject to change at any time. It is possible that governmental authorities will conclude that our
business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. Penalties for violations of applicable healthcare laws and regulations may include
significant civil, criminal and administrative penalties, damages, disgorgement, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and additional reporting requirements and oversight
if we enter into a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws. In addition, violations may also result in reputational harm, diminished profits and future earnings.
Because we use biological materials, hazardous materials, chemicals and radioactive compounds, if we do not comply with laws regulating
the protection of the environment and health and human safety, our business could be adversely affected.
Our research, development and manufacturing activities involve the use of potentially harmful biological materials as well as materials,
chemicals and various radioactive compounds that could be hazardous to human health and safety or the environment. We store most of these materials and various wastes resulting from their use at our facilities in Carlsbad, California pending ultimate
use and disposal. We cannot completely eliminate the risk of contamination, which could cause:
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interruption of our research, development and manufacturing efforts;
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injury to our employees and others;
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environmental damage resulting in costly clean up; and
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liabilities under federal, state and local laws and regulations governing health and human safety, as well as the use, storage, handling and disposal of these materials
and resultant waste products.
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In such an event, we may be held liable for any resulting damages, and any liability could exceed our resources. Although we carry
insurance for pollution liability in amounts and types that we consider commercially reasonable, the coverage or coverage limits of our insurance policies may not be adequate. If our losses exceed our insurance coverage, our financial condition would
be adversely affected.
Our business is subject to changing regulations for corporate governance and public disclosure that has increased both our costs and the
risk of noncompliance.
Each year we are required to evaluate our internal control systems to allow management to report on, and our Independent Registered Public
Accounting Firm to attest to, our internal controls as required by Section 404 of the Sarbanes-Oxley Act. As a result, we continue to incur additional expenses and divert our management’s time to comply with these regulations. In addition, if we cannot
continue to comply with the requirements of Section 404 in a timely manner, we might be subject to sanctions or investigation by regulatory authorities, such as the SEC, the Public Company Accounting Oversight Board, or PCAOB, or The Nasdaq Global
Select Market. Any such action could adversely affect our financial results and the market price of our common stock.
The SEC and other regulators have continued to adopt new rules and regulations and make additional changes to existing regulations that
require our compliance. In July 2010, the Dodd-Frank Wall Street Reform and Protection Act, or the Dodd-Frank Act, was enacted, and in August 2022, the SEC adopted additional rules and regulations under the Dodd-Frank Act related to “say on pay” and
proxy access. Stockholder activism, the current political environment and the current high level of government intervention and regulatory reform may lead to substantial new regulations and disclosure obligations, which has and may in the future lead
to additional compliance costs and impact the manner in which we operate our business.
Risks related to taxes
Our ability to use our net operating loss carryovers and certain other tax attributes may be limited.
Under the Internal Revenue Code of 1986, as amended, or the Code, a corporation is generally allowed a deduction for net operating losses,
or NOLs, carried over from a prior taxable year. Under the Code, we can carry forward our NOLs to offset our future taxable income, if any, until such NOLs are used or expire. The same is true of other unused tax attributes, such as tax credits.
Under the current U.S. federal income tax law, U.S. federal NOLs generated in taxable years beginning after December 31, 2017 may be
carried forward indefinitely, but the deductibility of such U.S. federal NOLs is limited to 80 percent of taxable income.
In addition, under Sections 382 and 383 of the Code, and corresponding provisions of state law, if a corporation undergoes an “ownership
change,” which is generally defined as a greater than 50 percentage-point cumulative change, by value, in its equity ownership over a three-year period, the corporation’s ability to use its pre-change NOL carryforwards and other pre-change tax
attributes to offset its post-change income or taxes may be limited. We may experience ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which may be outside of our control. If an ownership change occurs
and our ability to use our NOL carryforwards or other tax attributes is materially limited, it would harm our future operating results by effectively increasing our future tax obligations. As a result of our merger with Akcea Therapeutics, Inc. in
2020, or the Akcea Merger, we are subject to the separate return limitation year, or SRLY, rules. Under the SRLY rules, our utilization of Akcea’s pre-merger NOL and tax credit carryforwards is limited to the amount of income that Akcea contributes to
our consolidated taxable income. The Akcea pre-merger tax attributes cannot be used to offset any of the income that Ionis contributes to our consolidated taxable income. In addition, at the state level, there may be periods during which the use of
NOLs is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed. For example, in June 2024, California enacted Senate Bill 167, or SB 167, which, with certain exceptions, suspends the ability to use California
net operating losses to offset California income and limits the ability to use California business tax credits to offset California taxes, for taxable years beginning after 2023 and before 2027.
Our future taxable income could be impacted by changes in tax laws, regulations and treaties.
A change in tax laws, treaties or regulations, or their interpretation, of any country in which we operate could materially affect us.
We could be subject to additional tax liabilities.
We are subject to U.S. federal, state, local and foreign
income taxes, sales taxes in the U.S., withholding taxes and transaction taxes in foreign jurisdictions. Significant judgment is required in evaluating our tax positions and our worldwide provision for taxes. During the ordinary course of business,
there are many activities and transactions for which the ultimate tax determination is uncertain. In addition, our tax obligations and effective tax rates could be adversely affected by changes in the relevant tax, accounting and other laws,
regulations, principles and interpretations, including those relating to income tax nexus, by recognizing tax losses or lower than anticipated earnings in jurisdictions where we have lower statutory rates and higher than anticipated earnings in
jurisdictions where we have higher statutory rates, by changes in foreign currency exchange rates, or by changes in the valuation of our deferred tax assets and liabilities.
In particular, our tax obligations and effective tax rate in the
jurisdictions in which we conduct business could increase in the future as a result of the base erosion and profit shifting, or BEPS, project led by the Organization for Economic Co-operation and Development, or OECD, and other initiatives led by the
OECD or the European Commission. The OECD is leading work on an iteration of the BEPS project based on two “pillars” (subject to certain revenue thresholds), involving the reallocation of taxing rights in respect of certain multinational enterprises
above a fixed profit margin to the jurisdictions in which they carry on business) (referred to as “Pillar One”) and imposing a minimum effective corporate tax rate on certain multinational enterprises (referred to as “Pillar Two”). Based on the minimum
revenue thresholds we do not expect to fall within the scope of these requirements in the near term.
We may be audited in various jurisdictions, and such
jurisdictions may assess additional income, sales and value-added or other taxes against us. Although we believe our tax estimates are reasonable, the final determination of any tax audits or litigation could be materially different from our
historical tax provisions and accruals, which could have a material adverse effect on our operating results or cash flows in the period for which a determination is made
.
| ITEM 2. |
UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS
|
Not applicable.
| ITEM 3. |
DEFAULT UPON SENIOR SECURITIES
|
Not applicable.
| ITEM 4. |
MINE SAFETY DISCLOSURES
|
Not applicable.
| ITEM 5. |
OTHER INFORMATION
|
Trading Plans
During the quarter ended March 31, 2025,
our directors and officers (as defined in Rule 16a-1(f) under the Exchange Act), or Section 16 officers and directors, did not
adopt
or
terminate
contracts, instructions or written plans for the purchase or sale of our securities.
| ITEM 6. |
EXHIBITS
|
| a. |
Exhibits
|
|
Exhibit Number
|
Description of Document
|
|
|
Third Amended Non-Employee Director Compensation Policy.
|
||
|
License Agreement between Ionis Pharmaceuticals, Inc. and Ono Pharmaceutical Co., Ltd., dated March 10, 2025. Portions of this exhibit have been
omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.
|
||
|
Certification by Chief Executive Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended.
|
||
|
Certification by Chief Financial Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended.
|
||
|
32.1
*
|
Certification Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.
|
|
|
101
|
The following financial statements from the Ionis Pharmaceuticals, Inc. Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, formatted in Inline Extensible Business Reporting Language (iXBRL): (i) condensed consolidated balance sheets, (ii) condensed
consolidated statements of operations, (iii) condensed consolidated statements of comprehensive income (loss), (iv) condensed consolidated statements of stockholders’ equity, (v) condensed consolidated statements of cash flows and (vi) notes to
condensed consolidated financial statements (detail tagged).
|
|
|
104
|
Cover Page Interactive Data File (formatted in iXBRL and included in exhibit 101).
|
| * |
This certification is deemed not filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liability of that
section, nor shall it be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended.
|
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf
of the Registrant and in the capacities and on the dates indicated.
|
Signatures
|
Title
|
Date
|
||
|
/s/ BRETT P. MONIA
|
Director and Chief Executive Officer
|
|||
|
Brett P. Monia, Ph.D.
|
(Principal executive officer)
|
April 30, 2025
|
||
|
/s/ ELIZABETH L. HOUGEN
|
Executive Vice President, Finance and Chief Financial Officer
|
|||
|
Elizabeth L. Hougen
|
(Principal financial and accounting officer)
|
April 30, 2025
|
52
TABLE OF CONTENTS
Part I Financial InformationItem 1. Financial StatementsItem 2. Management S Discussion and Analysis Of Financial Condition and Results Of OperationsItem 3. Quantitative and Qualitative Disclosures About Market RiskItem 4. Controls and ProceduresPart II Other InformationItem 1. Legal ProceedingsItem 1A. Risk FactorsItem 2. Unregistered Sales Of Equity Securities and Use Of ProceedsItem 3. Default Upon Senior SecuritiesItem 4. Mine Safety DisclosuresItem 5. Other InformationItem 6. Exhibits