Alloy Therapeutics recently announced a collaboration and licensing agreement with Biogen, authorizing Biogen to use Alloy’s novel and proprietary AntiClastic™ antisense oligonucleotide (ASO) platform to advance antisense therapies targeting multiple undisclosed targets.

Alloy will receive an upfront payment and will be eligible for additional milestone payments and tiered royalties based on any products generated from the collaboration.

It is worth noting that Biogen has been deeply involved in the ASO field for many years and has the blockbuster ASO drug Spinraza in hand. This time, choosing to use an external platform to promote the development of the next-generation ASO pipeline is both an endorsement of the Alloy technology platform and an expectation for the next generation of ASO drugs.

01
Biogen's anxiety

In 2025, Boquan's annual revenue was $9.9 billion, failing to break the $10 billion mark for the third consecutive year, and far from its peak of $14.38 billion in 2019. More worryingly, the company's guidance for 2026 is that total revenue will decline by a mid-single-digit percentage compared to 2025.

Biogen's star product in the MS field, Tecfidera, has seen a precipitous decline in sales due to the impact of generic drugs . The drug peaked at $4.4 billion in sales in 2019, becoming a core pillar of the company's revenue. However, after its patent expired in 2020, Tecfidera faced competition from generic drugs, and its sales are projected to fall below $700 million by 2025. Meanwhile, Biogen's next-generation MS products are also proving less competitive in an era dominated by B-cell targeted therapies, leading to an overall decline in its MS business.

The market performance of Leqembi (lencanemab), a new Alzheimer's drug that was once highly anticipated , has also fallen short of expectations and failed to become a new growth engine.

Against this backdrop, Biogen is expanding its business through mergers and acquisitions while simultaneously strengthening its strengths through partnerships.

Biogen recently announced its acquisition of Apelliis Pharmaceuticals for approximately $5.6 billion, one of the largest acquisitions in the company's history. Apelliis' two marketed drugs—the ophthalmic drug SYFOVRE and the nephropathy drug EMPAVELI—are projected to generate a combined net sales of $689 million in 2025 and are expected to maintain double-digit growth until at least 2028, directly supplementing Biogen's immediate revenue.

In the ASO field, Biogen, as a veteran player, is collaborating with Alloy to innovate its technology platform and develop next-generation ASO drugs.

As early as 2012, Biogen entered into a strategic partnership with Ionis, acquiring the global rights to develop, manufacture, and commercialize the ASO drug nusinersen.

In 2016, nusinersen (brand name Spinraza) was approved for marketing in the United States for pediatric and adult patients with SMA, becoming the first gene therapy for SMA and opening the door to drug treatment for central nervous system diseases caused by ASO. In 2019, this drug was also approved for marketing in China.

After its launch, Spinraza became one of Biogen's growth engines, reaching a peak sales of $2.1 billion in 2019.

However, Spinraza continued to face pressure from Novartis' gene therapy Zolgensma and Roche's oral drug Evrysdi, with sales falling to $1.55 billion in 2025.
In response to the declining trend, Biogen launched a high-dose version of Spinraza in many parts of the world.

Meanwhile, the next-generation SMA ASO drug salanersen has entered global Phase III clinical trials. It is administered intrathecally, and Phase I data show that it is well tolerated. In patients with high baseline NfL concentrations, the marker decreased by 70% after 6 months of treatment, and the effect can last for one year, which is expected to achieve "one injection per year" and significantly reduce the burden on patients.

But Biogen's ASO ambitions go far beyond that.

In the field of Alzheimer's disease, the company's microtubule-associated protein tau (MAPT)-targeting ASO drug BIIB080, developed in collaboration with Ionis, is currently in Phase II clinical trials. Phase I data showed that in subjects treated with BIIB080, the concentration of total tau protein (t-tau) in cerebrospinal fluid decreased in a dose-dependent manner, with a maximum reduction of approximately 50%.

Furthermore, the collaboration agreement with Alloy allows Biogen to advance antisense therapies against multiple undisclosed targets, signifying that Biogen is systematically building its next-generation ASO pipeline.

02
Opportunities in the ASO (App Store Optimization) Track

In 2025, the global small nucleic acid drug market reached US$7.19 billion, and it is projected to continue expanding to US$17.7 billion between 2025 and 2030, growing at a robust CAGR of 19.7%. This expansion trend indicates that RNA-targeted therapies are gaining unprecedented clinical recognition and commercialization momentum in several key therapeutic areas.

According to data from PharmNet, there are more than 3,000 small nucleic acid drug candidates worldwide, of which nearly 600 ASO drugs are in different stages of development, involving more than 200 companies.

It's clear that the track is becoming popular but also increasingly crowded.

Alloy's core strength lies in its technology platform, which attracted Biogen, a veteran player in the ASO field, to choose to cooperate .

Alloy defines itself as a "biotechnology ecosystem company," empowering the future of drug discovery and development through AI-driven platforms and scientific expertise.

The company's commercialization logic is to provide partners with the right to use its technology platform, collecting upfront payments, milestone payments, and tiered royalties. The brilliance of this model lies in its "casting a wide net and sharing the benefits": it avoids the risk of clinical trial failures, yet can spread the platform's R&D costs through extensive collaborations, and reap the rewards when any drug succeeds.

Since its establishment in 2017, Alloy has signed approximately 200 collaborations, of which more than 100 have resulted in licensed drug candidates, and 22 drugs have entered the clinical stage, covering areas such as antibodies, gene therapy, cell therapy, and drug delivery.
Alloy's AntiClastic ASO platform aims to achieve "stronger efficacy, improved immunogenicity, and enhanced tissue targeting."

ASO therapy holds promise for reaching many untreatable intracellular targets at the nucleic acid level, but its development is limited by therapeutic index and delivery challenges.

The AntiClastic ASO platform engineeres oligonucleotides into unique spatial conformations, facilitating efficient delivery of antisense oligonucleotides to target RNA while minimizing interactions with unintended RNA targets and inflammatory responses, thereby providing a higher therapeutic index.

Drug candidates developed based on this platform have achieved significant improvements in efficacy compared to traditional antisense drugs. This platform is widely used to treat diseases by targeting genes expressed in the central nervous system (CNS), liver, muscles, and eyes.

Partners can either apply this proprietary conformation directly to existing antisense sequences or collaborate on the platform to discover novel AntiClastic oligonucleotide molecules, enabling precise payload delivery to target sites.

It is worth noting that Biogen is not the first major pharmaceutical company to choose the AntiClastic ASO platform.

In January 2025, Sanofi and Alloy entered into a collaboration worth over $400 million to develop central nervous system ASO therapies that can cross the blood-brain barrier using the AntiClastic platform, providing more effective treatment options for patients with CNS diseases.

Sanofi's foray into small nucleic acid research has been ongoing for some time. In 2011, it acquired Genzyme for $20.1 billion, which marked the beginning of its exploration of ASO drugs. It has continued to invest in ASO research and development since then, and now it is seeking breakthroughs by leveraging Alloy's platform capabilities.

03
Conclusion

Biogen maintains its leading position in the App Store Optimization (ASO) field with its two marketed products, Spinraza and Qalsody. However, competitive pressure has never subsided, and Spinraza's growth has stagnated, causing it to fall from its throne as the "king of small nucleic acid drugs."

Faced with the changing landscape, Biogen is both launching a defensive counterattack with a high-dose version of Spinraza and launching an offensive with next-generation pipelines such as Salanersen and BIIB080, as well as new collaborations, aiming to strengthen its long-term competitiveness in the ASO (App Store Optimization) market.

For Alloy, the successive choices made by leading pharmaceutical companies, from Sanofi to Biogen, are a continuous validation of the value of its ASO platform. For the ASO industry as a whole, this collaboration signals that ASO technology is entering a new cycle of iteration and upgrades, and platform capabilities are becoming a key variable defining the future competitive landscape.

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