Category: 3. Business

Introduction

The strategy has been published in accordance with paragraph 16(4) Schedule 19 Finance Act 2016. It cover the financial period ending December 31st, 2025.  The Strategy is refreshed annually and was last approved by the Board on 4th December 2025.  While this statement applies only to UK subsidiaries that are held under the control of the McLaren Group (“Mclaren”) a centralised approach to tax risk means that it is applied consistently across all group companies; a full list of the entities covered is enclosed in the Appendix. The statement will not apply to any companies divested during the period from the date of divesture and will apply to any acquired companies from the date of acquisition. 

McLaren operates in many countries, and we recognise our responsibility towards investors, governments, suppliers, employees, and the local communities we are part of. In the UK, the activities of the Group generate a substantial amount of taxes payable to HMRC across several different areas of tax legislation. We are liable for corporate income taxes, withholding taxes, stamp duties and employment taxes although this list is not exhaustive. Furthermore, we collect and pay employee taxes as well as indirect taxes such as excise duties and VAT. 

McLaren Group tax strategy

We believe it is important to state clearly and precisely our views on tax in the context of corporate responsibility. Our Tax Strategy sits within a framework of McLaren’s ethics and business values which promote a strong culture for our employees to be responsible corporate citizens. The McLaren Racing Code of Conduct explicitly states that ensuring that all our people display good and appropriate behaviour is a vital part of building high performing teams and reaching our goals in racing and business. Our overall ethical approach is based on a simple principle that we will endeavour to conduct all our external and internal dealings with fairness, integrity and professionalism. Our approach to tax aligns with that. We are committed to complying with tax laws in a responsible manner and to having open and constructive relationships with the tax authorities.

Tax governance and risk management

The responsibility for McLaren’s tax strategy and compliance ultimately rests with the Board of Directors for McLaren Group Limited. However, that responsibility is delegated to the Executive Boards of the operating companies with the Group Board of Directors applying oversight.  These Executive Boards will ensure the unified tax strategy is implemented and is aligned to the commercial, environmental and social issues that impact the businesses. The Senior Accounting Officer for the Group has responsibility for ensuring that policies and procedures that support the approach are in place, maintained, used consistently around their businesses and that the tax teams have the skills and experience to implement the approach appropriately. 

The Chief Financial Officer, supported by the Financial Controllers and Tax Teams, are responsible for identifying tax risks, devising robust policies and procedures, ensuring that these are maintained and used consistently around their businesses. These steps undertaken ensure that the Tax Strategy is achieved, tax risks are managed, and the correct amount of tax is paid. Oversight of the tax risks is conducted by the Group Audit and Risk Committee as part of their remit to review the Group risk exposures and maintain a sound system of risk management and internal control.

Tax planning

The Group will only engage in tax planning that supports our business and reflects commercial and economic activity. We do not engage in artificial tax arrangements or consider arrangements that avoid the payment of tax. For the avoidance of doubt, planning where the sole motivation is tax avoidance is not undertaken.  We conduct transactions between Group companies on an arm’s-length basis and in accordance with current guidelines issued by the Organisation for Economic Cooperation and Development (OECD).

McLaren Racing conducts research and development to develop the world’s most technologically advanced racing cars and to add value to our global blue-chip technology partners. By investing significantly in research and development we can develop new technologies which improve efficiency and contribute to the enhanced performance of critical industries including automotive, motorsport, transport and healthcare. In turn, we undertake to support economic growth and opportunity. Recognising the benefits to society of such work, tax incentives and exemptions are implemented by Governments and the Tax Authorities to support investment, employment and economic development. Where incentives exist, we will only claim and apply these in the manner that they are intended.

Transparency and relationships with tax authorities

We seek to build and sustain relationships with Tax Authorities that are constructive and based on mutual respect. We have regular dialogue with our Customer Relationship Manager and relevant specialists within HMRC. We meet our CCM periodically for a Business Risk Review meeting which addresses all the taxes and is a wide-ranging discussion of the UK tax affairs. 

McLaren seeks to reduce the level of tax risk arising from its commercial businesses to the minimum level by ensuring that a judicious approach is taken towards all our processes. We are committed to full compliance with all statutory obligations and full disclosure to tax authorities. We believe that our obligation is to pay the amount of tax legally due and to observe all applicable rules and regulations in all the territories in which we operate. Similarly, we have an obligation to maximise shareholder value and to control our tax costs. In achieving this balance, we believe that transparency regarding our position is the best policy. 

McLaren discloses all relevant facts in its computations and identifies any transactions or issues where it considers that there is potential for the tax treatment to be uncertain. Any inadvertent errors in submissions are fully disclosed as soon as reasonably practicable after they are identified.

Appendix

“The Group” or “McLaren” should be taken to mean the following UK entities for the purposes of this document:

•    McLaren Group Limited
•    McLaren Newco Limited
•    McLaren Racing Limited
•    McLaren Triple Crown Limited
•    McLaren Electric Racing Limited
•    Mile Marketing Limited
•    McLaren Marketing Limited – Dormant in 2025
•    McLaren Newco (No. 2) Limited – Dormant in 2025
•    McLaren Licensing Holdings Limited – Holding less than 50%

Prior to 3rd April 2025 the Group included the following UK entities:

•    McLaren Holdings Limited
•    McLaren Automotive Limited
•    McLaren Automotive Events Limited
•    McLaren Finance plc
•    Mclaren Services Limited
•    Mclaren Support Services Limited

AI is moving quickly into healthcare, bringing potential benefits but also possible pitfalls such as bias that drives unequal care and burnout of physicians and other healthcare workers. It remains undecided how it should be regulated in the U.S.

In September, the hospital-accrediting Joint Commission and the Coalition for Health AI issued recommendations for implementing artificial intelligence in medical care, with the burden for compliance falling largely on individual facilities.

I. Glenn Cohen, faculty director of Harvard Law School’s Petrie-Flom Center for Health Law, Biotechnology, and Bioethics, and colleagues suggested in the Journal of the American Medical Association that the guidelines are a good start, but changes to ease likely regulatory and financial burdens — particularly on small hospital systems — are needed.

In this edited conversation, Cohen, the James A. Attwood and Leslie Williams Professor of Law, discussed the difficulty of balancing thoughtful regulation with avoiding unnecessary roadblocks to game-changing innovation amid rapid adoption.

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Is it clear that AI in healthcare needs regulation?

Whenever medical AI handles anything with medium to high risk, you want regulation: internal self-regulation or external governmental regulation. It’s mostly been internal thus far, and there are differences in how each hospital system validates, reviews, and monitors healthcare AI.

When done on a hospital-by-hospital basis like this, costs to do this kind of evaluation and monitoring can be significant, which means some hospitals can do this, and some can’t. By contrast, top-down regulation is slower — maybe too slow for some forms of progress in this space.

There’s also a complicated mix of AI products going into hospitals. Some may assist with things like internal purchasing and review, but many more are clinical or clinically adjacent.

Some medical AI products interface directly with consumers, such as chatbots that people might be using for their mental health. For that, we don’t even have internal hospital review, and the need for regulation is much clearer.

With technology moving so fast, is speed important even in regulation?

This is an innovation ecosystem that has a lot of startup energy, which is great. But you’re talking about something that can scale extremely quickly, without a lot of internal review.

Whenever you enter what I call a “race dynamic,” there is a risk that ethics is left behind pretty quickly. Whether the race is to be the first to develop something, a race for a startup against money running out, or a national race between countries trying to develop artificial intelligence, the pressures of time and urgency make it easier to overlook ethical issues.

The vast majority of medical AI is never reviewed by a federal regulator — and probably no state regulator. We want to have standards for healthcare AI and an incentive to adopt standards.

But putting everything through the rigorous FDA process for drugs or even the one for medical devices would in many cases be prohibitively expensive and prohibitively slow for those enamored with the rate of development in Silicon Valley.

On the flip side, if they perform badly, many of these technologies are a much greater risk to the general populace than the average device on the market.

If you take an aspirin or a statin, there are differences in how they work in different people, but to a large extent we can characterize those differences ahead of time. When medical AI is reading an X-ray or doing something in the mental health space, how it’s implemented is key to its performance.

You might get very different results in different hospital systems, based on resources, staffing, training, and the experience and age of people using them, so one has to study implementation very carefully. This would create an unusual challenge for an agency like FDA — which often says it does not regulate the practice of medicine — because where the approval of an AI system stops and the practice of medicine begins is complicated.

Your study examines a regulatory system suggested by the Joint Commission, a hospital accreditor, and the Coalition for Health AI. Would an accreditor naturally be something that hospitals would — or would have to — pay attention to?

Exactly. In almost every state, in order to be able to bill Medicare and Medicaid you need to be accredited by the Joint Commission. This is a huge part of almost every hospital’s business.

There is a robust process to qualify for accreditation, and every so often you are re-evaluated. It’s serious business.

The Joint Commission hasn’t yet said that these AI rules are going to be part of our next accreditation, but these guidelines are a sign that they may be going in that direction.

“I speak about legal and ethical issues in this space, but I’m an optimist about this. I think that, in 10 years, the world will be significantly better off because of medical artificial intelligence.”

Do you find some of the recommendations wanting?

Some are more demanding than I expected, but I actually think they’re pretty good.

Requiring that — when appropriate — patients should be notified when AI directly impacts their care and that — when relevant — consent to use an AI agent should be obtained, is a strong position to take.

A lot of scholars and other organizations don’t take the position that medical AI should always be disclosed when it directly impacts care, let alone that informed consent should always be sought.

The guidelines also require ongoing quality monitoring and continual testing, validation, and monitoring of AI performance.

Monitoring frequency would scale to risk levels in patient care. These are good things to do, but difficult and expensive. You’ll have to assemble multidisciplinary AI committees and constantly measure for accuracy, errors, adverse events, equity, and bias across populations.

If taken seriously, it will probably be infeasible for many hospital systems in the U.S. They will have to make a threshold decision whether they’re going to be AI adopters.

You point out in your JAMA article that most hospitals in the U.S. are small community hospitals, and that resources are a major issue.

I am told by people in major hospital systems that already do this that to properly vet a complex new algorithm and its implementation can cost $300,000 to half a million dollars. That’s simply out of reach for many hospital systems.

There are actually going to be things in the implementation that are specific to each hospital, but there are also going to be things that might be valuable to know that are common for many hospital systems. The idea that we’d do the evaluation repeatedly, in multiple places, and not share what’s learned seems like a real waste.

If the answer is, “If you can’t play in the big leagues, you shouldn’t step up to bat,” that creates a have/have-not distribution in terms of healthcare access. We already have that as to healthcare generally in this country, but this would further that dynamic at the hospital level.

Your access to AI that helps medical care would be determined by whether you’re in networks of large academic medical centers that proliferate in places like Boston or San Francisco, rather than other parts of the country that don’t have that kind of medical infrastructure.

The goal, ideally, would be more centralization and more sharing of information, but these recommendations put a lot of the onus on individual hospitals.

Doesn’t a system where some hospitals can’t participate negate the potential benefits from this latest generation of AI, which can assist places that are resource-poor by providing expertise that might be missing or hard to find?

It would be a shame if you’ve got a great AI that’s helping people and might do the most benefit in lower-resource settings, and yet those settings are unable to meet the regulatory requirements in order to implement.

It would also be a sad reality, as an ethical matter, if it turns out that we’re training these models on data from patients across the country, and many of those patients will never get the benefit of these models.

If the answer is that the vetting and monitoring of medical AI should be done by a larger entity, is that the government?

The Biden administration’s idea was to have “assurance labs” — private-sector organizations that in partnership with the government could vet the algorithms under agreed-upon standards such that healthcare organizations could rely on them.

The Trump administration agrees on the problem but has signaled that they don’t like the approach. They have yet to fully indicate what their vision is.

It sounds like a complex landscape, as well as a fast-moving one.

Complex, but also challenging and interesting.

I speak about legal and ethical issues in this space, but I’m an optimist about this. I think that, in 10 years, the world will be significantly better off because of medical artificial intelligence.

The diffusion of those technologies to less-resourced settings is very exciting, but only if we align the incentives appropriately. That doesn’t happen by accident, and it is important that these distributional concerns be part of any attempt to legislate in the area.

SEATTLE — Jan. 12, 2026 — Fred Hutch Cancer Center welcomed Sabah Öney to its Board of Directors effective Jan. 1, 2026. Öney is the president and chief executive officer of Dispatch Bio, a start-up company that is engineering a universal treatment across solid tumors.

“It is an honor to join the Fred Hutch Board of Directors,” said Öney. “For the past 50 years, Fred Hutch has built a global reputation for developing lifesaving treatments and leading scientific innovation, and I look forward to joining with this outstanding group of leaders to advance the mission of curing cancer and infectious diseases.”

Öney brings nearly 20 years of scientific experience and executive leadership in the biotechnology industry. In 2012, he oversaw the global expansion of products at Ariosa Diagnostics. Later, he served as the Chief Business Officer of Alector, a biotech company leveraging the immune system against neurodegenerative diseases and guided the company throughout its IPO process. In 2021, he joined ARCH Venture Partners as a Venture Partner. Öney is also a Co-founder and Interim CEO of Vilya, a computational biotechnology company founded by Nobel Laureate David Baker, PhD, and serves on its Board of Directors.

His education experience reflects a combination of scientific innovation and business experience. Öney received his bachelor’s degree in genetics from the University of Kansas, his MBA from Stanford University Graduate School of Business and his PhD in Genetics and Genomics from Duke University. He is the co-author of numerous scientific publications and has developed several biotechnology patents.

Motivated both professionally and personally to advance immunotherapy treatment and research, Öney shares a passion for Fred Hutch’s mission to eliminate cancer and infectious diseases. In 2022, as part of Fred Hutch’s Climb to Fight Cancer Timmerman Traverse trek to the Everest Base Camp, he raised nearly $97,000 for cancer research at Fred Hutch and called the journey a “life-altering experience.”

“Sabah is an outstanding addition to our Board of Directors, bringing a wealth of experience in leading innovative biotechnology companies that are transforming the treatment of cancer and other diseases,” said Dr. Thomas J. Lynch, president and director of Fred Hutch and holder of the Raisbeck Endowed Chair. “As we now enter the next 50 years of Fred Hutch’s mission and legacy, Sabah’s insight will be instrumental in advancing our next chapter of scientific innovation and treatment.”

###

Media contact:

Shayla Ring

sring@fredhutch.org

Fred Hutch Cancer Center unites individualized care and advanced research to provide the latest cancer treatment options while accelerating discoveries that prevent, treat and cure cancer and infectious diseases worldwide.

Based in Seattle, Fred Hutch is an independent, nonprofit organization and the only National Cancer Institute-designated cancer center in Washington. We have earned a global reputation for our track record of discoveries in cancer, infectious disease and basic research, including important advances in bone marrow transplantation, immunotherapy, HIV/AIDS prevention and COVID-19 vaccines. Fred Hutch operates eight clinical care sites that provide medical oncology, infusion, radiation, proton therapy and related services. Fred Hutch also serves as UW Medicine’s cancer program.

Global law firm K&L Gates LLP served as legal counsel to Lightwave Logic, Inc., a technology platform company leveraging its proprietary electro-optic (EO) polymers to transmit data at higher speeds with less power in a small form factor, in connection with an underwritten public offering of its common stock. 

Lightwave sold 11,666,667 shares of common stock in the offering at a price of US$3.00 per share, resulting in gross proceeds of US$35 million. The common stock trades on the Nasdaq Capital Market under the ticker symbol “LWLG.” 

Lightwave plans to allocate the net proceeds to accelerate its commercialization timeline, accelerate and expand U.S. production capacity to support its customers, onboard additional large scale design-ins, pursue strategic M&A opportunities or invest in complementary technologies or businesses, and for working capital and other general corporate purposes. 

The Corporate deal team was led by Miami partner Clayton Parker, with support from Miami partner Erin Fogarty, Nashville partner Lauren Ammons, Seattle partner Robert Starin, and Miami associate Stephen Vinson. 

“This offering marks an important step in Lightwave’s commercialization journey. We were pleased to advise the company on a transaction that supports its ability to scale US production, deepen customer partnerships, and pursue strategic opportunities as demand for high performance photonics continues to grow,” said Parker.

K&L Gates’ Corporate practice is one of the most substantial in the legal industry, with hundreds of lawyers in offices across the globe providing clients with practical legal solutions in the structuring, financing, and completion of domestic, international, and cross-border transactions.

• Deliveries up 4% year on year to 793 commercial aircraft in 2025
• 1,000 gross orders recorded from 57 customers (889 net), including 49 A220s, 656 A320s, 100 A330neos, two A330 MRTTs and 193 A350s
• Record overall order backlog of 8,754 and for widebodies of 1,124 at year-end

Toulouse, France, 12 January 2026 – Airbus delivered 793 commercial aircraft to 91 customers globally in 2025 and registered 1,000 new gross orders in the Commercial Aircraft business. The backlog at the end of December 2025 increased to a new year-end record of 8,754 aircraft highlighting the strong market demand for Airbus’ product portfolio. In 2025, Airbus achieved another healthy book to bill above one.

In a continued complex and dynamic operating environment, deliveries in 2025 maintained an upward trajectory. The year witnessed several landmark deliveries and welcomed new operators of the A220, the A321XLR, the A330neo and the A350-1000 across all regions. Airbus also won repeat orders and key new customers in both single aisle and widebody campaigns. The widebody backlog reached a new year-end record of 1,124 aircraft. 

Airbus’ 2025, 2024 and 2023 aircraft deliveries

Airbus’ 2025 full year Financial Results will be disclosed on 19 February 2026.

• Approval is supported by data from the DEVOTE study which showed the benefit of the SPINRAZA 50 mg and 28 mg regimen in both treatment-naïve and previously-treated nusinersen patients with SMA¹
• Biogen is dedicated to partnering with the SMA community to advance care through scientific innovation and a commitment to enhancing outcomes for people living with SMA

CAMBRIDGE, Mass., Jan. 12, 2026 (GLOBE NEWSWIRE) — Biogen Inc. (Nasdaq: BIIB) today announced the European Commission (EC) has granted marketing authorization for a high dose regimen of SPINRAZA^® (nusinersen) which is comprised of 50 mg/5 mL and 28 mg/5 mL doses for the treatment of 5q spinal muscular atrophy (SMA). 5q SMA is the most common form of the disease and represents approximately 95% of all SMA cases.² The SPINRAZA European Union marketing authorization has been updated to include the high dose regimen. The new high dose regimen comprises a more rapid loading phase, two 50 mg loading doses administered 14 days apart and 28 mg maintenance dose injections every four months thereafter. Individuals transitioning from the 12 mg dose will receive one 50 mg dose in place of their next 12 mg dose, followed by 28 mg maintenance doses every four months thereafter. SPINRAZA is for intrathecal use by lumbar puncture by health care professionals experienced in performing lumbar punctures.

“Since its approval in the European Union in 2017, SPINRAZA has helped set a new standard in patient care and treated more than then 10,000 infants, children, teens and adults worldwide,” Priya Singhal, M.D., M.P.H., Executive Vice President and Head of Development at Biogen. “We are proud to introduce the high dose regimen of SPINRAZA, which we have developed to address the evolving needs of individuals living with SMA, and are deeply committed to bringing it to the European SMA community as quickly as possible. We are grateful for all of the contributions of the SMA community who made today’s approval possible.”

The EC approval is based on data from the three-part, Phase 2/3 DEVOTE study and its ongoing long-term extension. Results from the pivotal cohort of the study showed treatment-naïve, symptomatic infants who received the high dose regimen of SPINRAZA experienced statistically significant improvements in motor function as measured by the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), when compared to a prespecified matched sham (untreated) group from the ENDEAR study* (mean difference: 26.19 points; +15.1 vs. -11.1, p<0.0001). Improvements in motor function were also observed in the open label cohort of individuals across a broad range of ages and SMA types who transitioned from the low dose regimen. These participants experienced a mean improvement on the Hammersmith Functional Motor Scale – Expanded of 1.8 points [SD 3.99] from baseline to Day 302.¹

“The DEVOTE results provide encouraging evidence that this new dosing option could deliver meaningful treatment outcomes with a safety profile generally consistent with the 12 mg dosing regimen,” said Eugenio Mercuri, M.D., Ph.D., Professor of Pediatric Neurology at the Catholic University, Rome, Italy. “I have witnessed the remarkable strides that have been made in treating SMA, but it is clear challenges remain. The European Commission approval of the high dose regimen of SPINRAZA is an important step toward addressing those challenges and advancing how we care for people living with SMA.”

Throughout the study, high dose regimen was generally well tolerated, with reported adverse events consistent with SMA and the known safety profile of nusinersen. No new safety concerns were observed with continued use of high dose nusinersen in the long-term-extension study. In the DEVOTE study, the most common adverse events that occurred in at least 10% of participants treated with the high dose regimen and occurred at least 5% more frequently than the matched sham group were pneumonia, COVID-19, pneumonia aspiration, and malnutrition.¹

Special warnings and precautions for use of nusinersen include adverse reactions as a part of the lumbar puncture procedure, low platelet counts and blood clotting abnormalities, renal toxicity and hydrocephalus (excessive buildup of cerebrospinal fluid in the brain).³

“As a community, we welcome advances that expand options for people living with SMA and reinforce continued innovation in SMA care,” said Nicole Gusset, CEO of SMA Europe. “This approval highlights the importance of sustained research and investment, contributing to a wider range of possibilities that may enable more tailored approaches to SMA care over time.”

The updated Summary of Product Characteristics will be available on the European Medicines Agency website at www.ema.europa.eu. 

The high dose regimen of SPINRAZA is also approved in Japan and is under review with the U.S. Food and Drug Administration (FDA) with a decision expected by April 3, 2026. Biogen is working with regulatory authorities around the world to progress this additional dosing option for people living with SMA. 

*ENDEAR is one of the two pivotal studies that formed the basis of regulatory approvals for SPINRAZA 12 mg.

About the DEVOTE Study¹
DEVOTE was a Phase 2/3 randomized, controlled, dose-escalating study designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of SPINRAZA when administered at a higher dose (50/28 mg). The study enrolled 145 participants across ages and SMA types at approximately 42 sites around the world. DEVOTE included an open-label safety evaluation cohort (Part A), a double-blind, active control randomized treatment cohort (Part B), followed by an open-label treatment cohort (Part C) to assess the safety and tolerability of transitioning participants from the currently approved dose of SPINRAZA 12 mg to the higher dose regimen being tested in the study.

Part B was comprised of a pivotal cohort in treatment-naïve patients with infantile-onset SMA (n=75), and a supportive cohort in treatment-naïve patients with later-onset SMA (n=24). The primary endpoint of Part B measured the change from baseline on CHOP-INTEND at six months, comparing the high dose regimen of nusinersen to a matched, untreated sham control group from the Phase 3 ENDEAR study. ENDEAR is one of the two pivotal studies that formed the basis of regulatory approval for SPINRAZA 12 mg.

Part C was an open-label evaluation of the higher dose regimen in children and adults who transitioned from SPINRAZA 12 mg to the 50/28 mg regimen (n=40).

About SPINRAZA
The high dose regimen of SPINRAZA (nusinersen) which is comprised of 50 mg/5 mL and 28 mg/5mL injections are approved in the European Union and Japan to treat infants, children and adults with spinal muscular atrophy (SMA). The high dose regimen of nusinersen is currently under review with the U.S. Food and Drug Administration (FDA) with a decision expected by April 3, 2026. SPINRAZA 12 mg/5 mL injection is approved for SMA in more than 71 countries.⁴

The low dose regimen of SPINRAZA has shown efficacy across ages and SMA types with a well-established safety profile based on data in patients treated up to 10 years,^5,6 combined with unsurpassed real-world experience. The most common adverse events observed in clinical studies were respiratory infection, fever, constipation, headache, vomiting and back pain. Laboratory tests can monitor for renal toxicity and coagulation abnormalities, including acute severe low platelet counts, which have been observed after administration of some ASOs. 

Biogen licensed the global rights to develop, manufacture and commercialize SPINRAZA from Ionis Pharmaceuticals, Inc. (Nasdaq: IONS). For more information, visit your respective country’s product website. For the U.S., please click here for Important Safety Information and full Prescribing Information .

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. Follow us on social media – Facebook, LinkedIn, X, YouTube.

Biogen Safe Harbor
This news release contains forward-looking statements, including, among others, relating to: the potential benefits, efficacy and safety of higher doses of nusinersen (marketed as SPINRAZA); the potential to improve outcomes for, and address unmet needs of, patients with SMA; potential regulatory discussions, submissions, decisions and approvals and the timing thereof; the anticipated benefits, risks and potential of our collaboration arrangements; the potential of our commercial business and pipeline programs, including nusinersen; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “forecast,” “goal,” “guidance,” “hope,” “intend,” “may,” “objective,” “outlook,” “plan,” “possible,” “potential,” “predict,” “project,” “prospect,” “should,” “target,” “will,” “would” or the negative of these words or 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 trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements. Given their forward-looking nature, these statements involve substantial risks and uncertainties that may be based on inaccurate assumptions and could cause actual results to differ materially from those reflected in such statements.

These forward-looking statements are based on management’s current beliefs and assumptions and on information currently available to management. Given their nature, we cannot assure that any outcome expressed in these forward-looking statements will be realized in whole or in part. We caution that these statements are subject to risks and uncertainties, many of which are outside of our control and could cause future events or results to differ materially from those stated or implied in this document, including, among others, uncertainty of our long-term success in developing, licensing, or acquiring other product candidates or additional indications for existing products; expectations, plans, prospects and timing of actions relating to product approvals, approvals of additional indications for our existing products, sales, pricing, growth, reimbursement and launch of our marketed and pipeline products; the potential impact of increased product competition in the biopharmaceutical and healthcare industry, as well as any other markets in which we compete, including increased competition from new originator therapies, generics, prodrugs and biosimilars of existing products and products approved under abbreviated regulatory pathways; our ability to effectively implement our corporate strategy; difficulties in obtaining and maintaining adequate coverage, pricing, and reimbursement for our products; the drivers for growing our business, including our dependence on collaborators and other third parties for the development, regulatory approval, and commercialization of products and other aspects of our business, which are outside of our full control; risks related to commercialization of biosimilars, which is subject to such risks related to our reliance on third-parties, intellectual property, competitive and market challenges and regulatory compliance; the risk that positive results in a clinical trial may not be replicated in subsequent or confirmatory trials or success in early stage clinical trials may not be predictive of results in later stage or large scale clinical trials or trials in other potential indications; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; and the occurrence of adverse safety events, restrictions on use with our products, or product liability claims; and any other risks and uncertainties that are described in reports we have filed with the U.S. Securities and Exchange Commission, which are available on the SEC’s website at www.sec.gov.

These statements speak only as of the date of this press release and are based on information and estimates available to us at this time. Should known or unknown risks or uncertainties materialize or should underlying assumptions prove inaccurate, actual results could vary materially from past results and those anticipated, estimated or projected. Investors are cautioned not to put undue reliance on forward-looking statements. A further list and description of risks, uncertainties and other matters can be found in our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and in our subsequent reports on Form 10-Q. Except as required by law, we do not undertake any obligation to publicly update any forward-looking statements whether as a result of any new information, future events, changed circumstances or otherwise.

Digital Media Disclosure
From time to time we have used, or expect in the future to use, our investor relations website (investors.biogen.com), the Biogen LinkedIn account (linkedin.com/company/biogen-) and the Biogen X account (https://x.com/biogen) as a means of disclosing information to the public in a broad, non-exclusionary manner, including for purposes of the SEC’s Regulation Fair Disclosure (Reg FD). Accordingly, investors should monitor our investor relations website and this social media channel in addition to our press releases, SEC filings, public conference calls and webcasts, as the information posted on them could be material to investors.

References:

1. Crawford TO, et al. Exploring Higher Doses of Nusinersen in Spinal Muscular Atrophy: Final Results From Parts B and C of the 3-Part DEVOTE Study. Presented at: World Muscle Society (WMS) Congress; 2024; Prague, Czechia.
2. Farrar MA, Kiernan MC. The Genetics of Spinal Muscular Atrophy: Progress and Challenges. Neurotherapeutics; 2015; 12:290–302.
3. European Medicines Agency. SPINRAZA Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/spinraza-epar-product-information_en.pdf. Last accessed: December 2025.
4. Based on commercial patients, early access patients, and clinical trial participants through December 31, 2022. 
5. Core Data sheet, Version 13, October 2021. SPINRAZA. Biogen Inc, Cambridge, MA.
6. Finkel RS, et al. Final Safety and Efficacy Data From the SHINE Study in Participants With Infantile-Onset and Later-Onset SMA. Presented at: Cure SMA Conference; 2024; Austin, Texas.

We thus collect all the parameters estimated from the data in a vector $\mathit{\pi }=(h,q_d,q_0,K)$. As we will better detail in the Methods, we develop a moment matching inference algorithm to infer the model parameters $\mathit{\theta }$, as depicted in Figure 1. The idea of the method is to introduce a cost function $\mathcal{C}(\mathit{\theta }|\mathit{\pi })$, representing a total relative error for some self-consistent equations. If the parameters $\mathit{\theta }$ are such that the right part of the self-consistent equation equals the left part, the problem is considered solved. Because the landscape associated with this cost function presents several minima, we perform multiple optimization procedures to collect an ensemble of possible solutions, from which we retain the top 30. First, we find that different solutions ${\mathit{\theta }}^{\ast }$ of the optimization problem provide ecological insights into the underlying microbiome populations.

As originally predicted in Altieri et al., 2021, among all the parameters that define Equation 1, the only ones relevant for reproducing the theoretical phase diagram are the amplitude of demographic noise and the heterogeneity of interactions. The mean interaction strength, provided it is sufficiently positive, does not play a significant role. This prediction is fully confirmed by the inference procedure applied to the two microbiome datasets, allowing us to identify a universal signature that distinguishes healthy from unhealthy states. Figure 3a shows, indeed, that inferred noise ($T$) and interaction heterogeneity strength ($\sigma$) for healthy and diseased microbiomes are clustered in the two-dimensional plane.

In particular, the SAD for the healthy cohort is robust among the different solutions of the inference procedure, as depicted by the superposition of the different curves in the inset of Figure 3a. On the other hand, SADs inferred from unhealthy patients have high sensitivity to different solutions. In particular, some of them display a mode for high-abundance species (light red lines in Figure 3a), a signature of dominant strain in the gut. Consistently, the distribution of the interactions $P({\alpha }_{i,j})$ generated through the inferred parameters μ and σ is different between healthy and diseased cohorts, giving a distinct pattern of interactions (see Figure 3b), a result that is compatible with that found by Bashan et al., 2016. Remarkably, we find that dysbiosis reduces the heterogeneity of interaction strengths, a result also observed when taking correlations as a proxy for interactions (Seppi et al., 2023).

We then assess how close the inferred σ and $\beta =1/T$ (a.k.a. inverse temperature in a statistical physics approach) are to the critical RSB line of the dgLV ($\mathcal{R}=0$), evaluated by keeping all the other parameters constant (see Methods). We find again that the replicon values $\mathcal{R}$ corresponding to each solution of our optimization protocol are significantly different for the two investigated microbiome phenotypes (see Figure 4a). In particular, diseased microbiomes are closer to marginal stability within the RS ansatz (Altieri et al., 2021; Mézard et al., 1987; de Almeida and Thouless, 1978). Furthermore, by investigating the shape of the SAD given by Equation 2, we can estimate the ratio between niche (represented by species interaction) and neutral (represented by birth/death and immigration) ecological forces, which can be captured by the quantity $\psi$ (Wu et al., 2021). It detects the emergence of peaks in the SAD as a hallmark of niche processes (see Appendix 2).

Inspired by field-theory arguments (see Methods and Appendix, Section S2), we can call the mass of the theory the $m$ parameter, as defined above in Equation 2. In classical and quantum field theory, the particle–particle interaction embedded in the quadratic term is typically referred to as a mass source. In our context, $m=1-\beta {\sigma }^2(q_d-q_0)$ captures quadratic fluctuations of species abundances, as also appearing in the expression of the leading eigenvalue of the stability matrix. When $m\to 0$, the analytical order parameters diverge and the system enters the unphysical regime of unbounded growth. As such, the mass term can be considered a complementary stability measure, capable of capturing the transition to the unbounded growth regime.

In the model, two kinds of effects compete to shape the community structure. On the one hand, we have niche effects, encoded in disordered interactions and thus tracked by the parameters μ, σ, and $K$. Their overall effect is selective and tends to concentrate the SAD around the typical abundance value. On the other hand, we have neutral effects encoded in the stochastic dynamics and immigration, governing the low-abundance regime of the SAD. When the demographic noise amplitude is stronger than immigration ($\nu <1$, as in our case), the SAD exhibits a low-abundance integrable divergence. In the opposite scenario, for $\nu >1$, there is no divergence, and the SAD is modal. Since interactions are random, the probability of observing an internal mode can be estimated as the fraction of SADs realizations having non-trivial solutions to the stationary point equation. Such a quantity, dubbed as the niche–neutral ratio, can be analytically evaluated:

(5)

${\displaystyle {\displaystyle {\displaystyle \psi =\frac{1}{2}\text{Erfc}\left(\frac{{\zeta }^{\ast }+\overline{\zeta }}{\sqrt{2}{\sigma }_{\zeta }}\right)+\frac{1}{2}\text{Erfc}\left(\frac{{\zeta }^{\ast }-\overline{\zeta }}{\sqrt{2}{\sigma }_{\zeta }}\right),}}}$

where ${\zeta }^{\ast }=\sqrt{\frac{4(1-\nu )m}{\beta }}$ and $\overline{\zeta }=K-\mu h$. When $\psi \approx 1$, niche and neutral forces give comparable contributions to the dynamics, as both low-abundance divergence and a finite abundance mode coexist in the SAD. Finally, if the typical abundance diverges, we enter the unbounded growth phase, which means that the mass $m$ and the niche–neutral ratio $\psi$ are not independent, as suggested by the analytical expression for $\psi$. For an exhaustive derivation of this result, see Appendix 2. With the obtained model parameters, we are able to evaluate $m$ and $\psi$ for healthy and diseased microbiomes. Also, in this case, healthy and diseased microbiomes are visibly clustered, as shown in Figure 4. Unhealthy microbiomes turn out to be closer to the unbounded growth phase, and the niche–neutral ratio is larger by five orders of magnitude than the healthy case ${\psi }_D\approx {10}^5{\psi }_H$. This leads us to argue that selective pressure is way larger in diseased states, while in the healthy one, birth and death effects are the key drivers of the dynamics. These results are also confirmed by the SAD shapes in the inset of Figure 3 (panel a).

In summary, in the Results section, we show that (i) the inference pipeline robustly recovers demographic noise and interaction heterogeneity by calculating $h$, $q_0$, and $q_d$ from the data; and (ii) these parameters cluster according to health status, with diseased microbiomes lying closer to the replica-symmetry-breaking threshold, indicating reduced ecological resilience.