* Development of BIIB105, an investigational antisense oligonucleotide for
amyotrophic lateral sclerosis (ALS), will be discontinued based on data from

    the Phase 1/2 ALSpire study
  * Biogen and Ionis continue their long-standing commitment to developing
    therapies for ALS given the devastating impact of this progressive, fatal
    neurodegenerative condition

CAMBRIDGE, Mass. and CARLSBAD, Calif., May 16, 2024 (GLOBE NEWSWIRE) -- Biogen
(http://www.biogen.com) Inc. (Nasdaq: BIIB) and Ionis Pharmaceuticals, Inc.
(https://www.ionispharma.com/) (Nasdaq: IONS) announced the decision to
terminate development of BIIB105 (ION541) an investigational antisense
oligonucleotide (ASO) for amyotrophic lateral sclerosis (ALS) based on topline
results from the Phase 1/2 ALSpire study. BIIB105 was designed to reduce
expression of ataxin-2 (ATXN2) protein and demonstrated statistically
significant cerebrospinal fluid (CSF) ATXN2 protein reductions in the study.
However, over the 6-month placebo-controlled period, treatment with BIIB105 did
not result in a reduction in levels of plasma neurofilament light chain (NfL), a
marker of neurodegeneration and neuronal damage. Additionally, BIIB105 did not
demonstrate an impact on clinical outcome measures of function, breathing, and
strength.
"While BIIB105 lowered ATXN2 protein, it did not reduce neurofilament, which
gives us confidence that BIIB105 did not slow the disease process," said
Stephanie Fradette, Pharm.D., Head of the Neuromuscular Development Unit at
Biogen. "We are deeply grateful for the contributions of the study participants
and remain committed to developing treatments that can meaningfully change the
disease trajectory for people living with ALS."
"We are very appreciative of the people with ALS and investigators who
participated in this study and were critical to advancing our scientific
understanding of ALS," said Frank Bennett, Ph.D., executive vice president and
chief scientific officer of Ionis. "Ionis continues to be committed to the ALS
community and is advancing our Phase 3 ulefnersen program for people with the
genetic form of the disease known as FUS-ALS."
Longer-term biomarker and efficacy data from the open-label-extension were
similar to those seen during the 6-month placebo-controlled treatment period,
with sustained reductions in ATXN2 but no impact on NfL or clinical outcome
measures over 40+ weeks of follow up. No evidence of benefit was observed in any
subgroup evaluated, including those participants with a Poly-CAG expansion in
the ATXN2 gene.
The Phase 1/2 study was a randomized, placebo-controlled, dose-escalating trial
to evaluate BIIB105 administered intrathecally to adults (n=99) with ALS.
Participants were randomized to receive BIIB105 or placebo (3:1 or 2:1 ratio)
for 3 to 6 months. Participants who completed the placebo-controlled period were
eligible to enroll in the open-label extension.
During the 6-month placebo-controlled portion of the study, the most common
adverse events (AEs) in BIIB105 treated participants were procedural pain,
headache and fall. AEs leading to study discontinuation were higher in the
BIIB105 group (8.3%) compared with the placebo group (3.6%).
Analyses of data from the study are ongoing to further understanding of the
underlying disease process and effects of BIIB105. The companies will present
the BIIB105 Phase 1/2 data at the upcoming European Network to Cure ALS (ENCALS)
meeting in Stockholm, Sweden in June.
Biogen's Continuous Commitment to ALS
For over a decade, Biogen has been committed to advancing ALS research to
provide a deeper understanding of all forms of the disease. The company has
continued to invest in and pioneer research despite making the difficult
decision to discontinue a late-stage ALS asset in 2013. Biogen has applied
important learnings to its portfolio of assets for genetic and other forms of
ALS, with the goal of increasing the probability of bringing a potential therapy
to patients in need. These applied learnings include evaluating genetically
validated targets in defined patient populations, pursuing the most appropriate
modality for each target and employing sensitive clinical endpoints. In addition
to QALSODY(®) (tofersen), the first treatment to target a genetic cause of ALS,
which was discovered by Ionis, the company has a robust discovery pipeline
including efforts to address TDP43 pathology for the broad ALS population. TDP43
pathology is seen in 97% of ALS cases and is considered a hallmark of the
disease.
About Biogen
Founded in 1978, Biogen is a leading biotechnology company that pioneers
innovative science to deliver new medicines to transform patients' lives and to
create value for shareholders and our communities. We apply deep understanding
of human biology and leverage different modalities to advance first-in-class
treatments or therapies that deliver superior outcomes. Our approach is to take
bold risks, balanced with return on investment to deliver long-term growth.
We routinely post information that may be important to investors on our website
at www.biogen.com (https://www.biogen.com/). Follow us on social media -
Facebook (https://www.facebook.com/Biogen/), LinkedIn
(https://www.linkedin.com/company/biogen-/), X (https://twitter.com/biogen),
YouTube (https://www.youtube.com/c/biogen).
About Ionis Pharmaceuticals, Inc.
For three decades, Ionis has invented medicines that bring better futures to
people with serious diseases. Ionis currently has five marketed medicines and a
leading pipeline in neurology, cardiology, and other areas of high patient need.
As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in
RNA therapies in addition to advancing new approaches in gene editing. A deep
understanding of disease biology and industry-leading technology propels our
work, coupled with a passion and urgency to deliver life-changing advances for
patients.
To learn more about Ionis, visit Ionispharma.com (https://www.ionispharma.com/)
and follow us on X (https://twitter.com/ionispharma) (Twitter) and LinkedIn
(https://www.linkedin.com/company/ionis-pharmaceuticals/).
About Ionis' Neurology Franchise
Ionis' neurology franchise addresses all major brain regions and central nervous
system cell types and currently has three Phase 3 studies ongoing with 11
therapies in clinical development, several of which Ionis plans to commercialize
directly. Ionis is discovering and developing potential treatments for many
neurological diseases for which there are few or no disease modifying
treatments, including common diseases like Alzheimer's and Parkinson's as well
as rare diseases such as amyotrophic lateral sclerosis (ALS) and Alexander
disease. Ionis has discovered and developed three commercially available
neurological disease medicines, including the first approved treatment for
spinal muscular atrophy, a medicine to treat hereditary transthyretin-mediated
amyloid polyneuropathy (ATTRv-PN), and, most recently, QALSODY for SOD1-ALS.
Biogen Safe Harbor
This news release contains forward-looking statements, about the treatment of
ALS; the anticipated benefits and potential of Biogen's collaboration
arrangements with Ionis; the potential of Biogen's commercial business and
pipeline programs; and risks and uncertainties associated with drug development
and commercialization. These statements may be identified by words such as
"aim," "anticipate," "believe," "could," "estimate," "expect," "forecast,"
"intend," "may," "plan," "possible," "potential," "will," "would" and other
words and terms of similar meaning. Drug development and commercialization
involve a high degree of risk, and only a small number of research and
development programs result in commercialization of a product. Results in early-
stage clinical studies may not be indicative of full results or results from
later stage or larger scale clinical studies and do not ensure regulatory
approval. You should not place undue reliance on these statements.
These statements involve risks and uncertainties that could cause actual results
to differ materially from those reflected in such statements, including without
limitation unexpected concerns that may arise from additional data, analysis or
results obtained during clinical studies; the occurrence of adverse safety
events; risks of unexpected costs or delays; the risk of other unexpected
hurdles; regulatory submissions may take longer or be more difficult to complete
than expected; regulatory authorities may require additional information or
further studies, or may fail or refuse to approve or may delay approval of
Biogen's drug candidates, including lecanemab; actual timing and content of
submissions to and decisions made by the regulatory authorities regarding
lecanemab; uncertainty of success in the development and potential
commercialization of lecanemab; failure to protect and enforce Biogen's data,
intellectual property and other proprietary rights and uncertainties relating to
intellectual property claims and challenges; product liability claims; and third
party collaboration risks, results of operations and financial condition. The
foregoing sets forth many, but not all, of the factors that could cause actual
results to differ from Biogen's expectations in any forward-looking statement.
Investors should consider this cautionary statement as well as the risk factors
identified in Biogen's most recent annual or quarterly report and in other
reports Biogen has filed with the U.S. Securities and Exchange Commission. These
statements speak only as of the date of this news release. Biogen does not
undertake any obligation to publicly update any forward-looking statements.
Ionis Forward-looking Statements
This press release includes forward-looking statements regarding Ionis'
business, financial guidance and the therapeutic and commercial potential of our
commercial medicines, additional medicines in development and technologies. Any
statement describing Ionis' 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 including 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.
Ionis' forward-looking statements also involve assumptions that, if they never
materialize or prove correct, could cause its results to differ materially from
those expressed or implied by such forward-looking statements. Although Ionis'
forward-looking statements reflect the good faith judgment of its management,
these statements are based only on facts and factors currently known by Ionis.
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. These and other risks concerning Ionis'
programs are described in additional detail in Ionis' annual report on Form 10-K
for the year ended December 31, 2023, and most recent Form 10-Q, which are on
file with the Securities and Exchange Commission. Copies of these and other
documents are available from the Company.
In this press release, unless the context requires otherwise, "Ionis,"
"Company," "we," "our" and "us" all refer to Ionis Pharmaceuticals and its
subsidiaries.
Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc.

 MEDIA CONTACT(S):                       INVESTOR CONTACT(S):
 Biogen                                  Biogen
 Jack Cox                                Chuck Triano
 + 1 781 464 3260                        +1 781 464 2442
 public.affairs@biogen.com               IR@biogen.com
 (mailto:public.affairs@biogen.com)      (mailto:IR@biogen.com)
 Ionis                                   Ionis
 Hayley Soffer                           D. Wade Walke, Ph.D.
 +1 760 603 4679                         +1 760 603 2331
 CorporateCommunications@ionisph.com     info@ionisph.com

(mailto:CorporateCommunications@ionisph (mailto:info@ionisph.com)
.com)
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