Ipsen and Skyhawk Therapeutics Announce $1.8B Collaboration to Develop RNA-Targeting Small Molecules for Rare Neurological Diseases

On April 22, 2024, Ipsen (Euronext: IPN; ADR: IPSEY) and Skyhawk Therapeutics announced the signing of a global exclusive collaboration agreement to discover and develop novel small molecules that modulate RNA in rare neurological diseases. The agreement includes an option, under which Ipsen will obtain global exclusive development rights to advance successful Development Candidates (DC). Upon successfully obtaining DC, Ipsen will be responsible for subsequent series of development activities. Skyhawk’s proprietary platform accelerates the R&D progress of RNA-targeting small molecules across multiple therapeutic areas, including rare neurological diseases.

According to the terms of the agreement, Skyhawk is eligible to receive up to $1.8 billion (approximately 13 billion RMB) in development, regulatory, and commercial milestones, including upfront payments for options and research collaboration, as well as potential tiered royalties.

Partnering with Multiple Giants, Focusing on Neurological Diseases

Skyhawk Therapeutics, Inc. was co-founded by Kathleen McCarthy and Bill Haney in 2016. It has completed three rounds of financing, including seed round and Series A round, with a total financing amount exceeding 180 million US dollars.

McCarthy has previously worked at the Spinal Muscular Atrophy (SMA) Foundation and Roche, where he participated in the development of small molecule therapies for spinal muscular atrophy (currently, gene therapy and antisense oligonucleotides have already been approved for treating this disease). After advancing innovative small molecule therapies to the clinical stage at Roche, McCarthy reached out to his old friend Haney—a documentary filmmaker, entrepreneur, and CEO of the startup Dragonfly Therapeutics—to co-found a separate company, Skyhawk Therapeutics, to continue the development of this promising therapy.

According to the research project involving McCarthy, RNA splicing errors may lead to the loss of mRNA expression levels, resulting in a series of neurological diseases including neuroblastoma, amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), frontotemporal dementia (FTD), and spinal muscular atrophy (SMA). Skyhawk's SkySTAR technology platform is a platform for discovering innovative small molecule drugs targeting RNA. It can be used to identify small molecule compounds that correct RNA splicing errors in the nucleus by binding to precursor RNA, thereby restoring mRNA expression levels.

Based on this, Skyhawk Therapeutics' proprietary SkySTAR™ technology platform stands for "Skyhawk Selective Splicing RNA Small Molecule Therapies." The platform aims to integrate data from computational, kinetic, and structural models of RNA to generate a unique and selective family of compounds for each target. These databases are tested using proprietary assays in patient cells to rapidly produce effective drug candidates.

According to the company's official statement, the proprietary platform approach aims to correct potential disease-causing genes at the mRNA level within the cell nucleus. The goal is to target key transcription factors and previously undruggable targets in major neurological diseases, immunology, inflammation, and infectious diseases.

The company also has the SKYLIBRARY™ technology platform, a customized and rapidly expandable RNA-targeting compound library. The SKYSEQ™ technology platform is a multiplex screening system capable of simultaneously testing dozens of high-value targets across a series of RNA motifs to identify compounds selective for specific disease targets. The SKYAI™ technology platform is a machine learning tool that integrates data from SKYSTAR, medicinal chemistry, animal studies, toxicology data, and clinical programs to drive the development of next-generation novel RNA splicing modulators.

Skyhawk's pipeline products cover cancer, neurological diseases, and fibrosis (including cirrhosis, hepatitis, non-alcoholic steatohepatitis, chronic kidney disease, myocardial infarction, heart failure, idiopathic pulmonary fibrosis, diabetes, and scleroderma, among other related diseases); the product pipelines in the fields of oncology and fibrosis have not yet been disclosed.

Among the four pipeline products in the field of neurological diseases, the two pipelines targeting Frontotemporal Dementia (FTD) and Spinocerebellar Ataxia Type 3 are still in the pre-IND stage; SKY-1214 for Multiple Myeloma/Non-Hodgkin's Lymphoma and SKY-0515 for Huntington's Disease have entered clinical trials, with SKY-0515 having completed Phase 1 clinical trials.

Notably, as of the end of March 2024, Skyhawk's partners include several major pharmaceutical companies such as Biogen, Takeda, Celgene, Genentech, and Merck, demonstrating the industry's attention to the company's small-molecule drug development platform targeting RNA splicing.

Among them, the partnership with Merck and Biogen in 2019 became a significant boost for Skyhawk in advancing its product pipeline. The collaboration agreement that year included Skyhawk using its SkySTAR™ technology platform to assist Merck in developing innovative small molecules targeting RNA splicing, as a potential new approach for treating certain neurological disorders and cancers. Earlier, Skyhawk had also announced an expansion of its collaboration agreement with Biogen: Biogen obtained additional exclusive global R&D rights beyond the original collaborative research phase, with candidate drugs potentially useful for treating multiple sclerosis, SMA, and other neurological diseases.

Giants and Startups: The Multi-Party Battle in Targeted RNA Small Molecule Drugs

For Skyhawk, which boasts an impressive track record, Ipsen is merely the latest addition to its star-studded list of R&D partners. In fact, Ipsen had already set aside €1.9 billion (US$2 billion) in 2023 for external innovation and officially made its move in April 2024.

Details of the products Ipsen will develop after signing the cooperation agreement have not been disclosed yet. Aside from the rare neurological disorders covered by the agreement, Ipsen only stated that it would leverage its "neuroscience expertise in movement disorders" to develop and commercialize these small-molecule drugs.

The reason why Ipsen has set its sights on Skyhawk can be traced to the existing RNA-targeted drugs: In recent years, RNA-targeted drugs have matured, but almost all of them are administered via injection or infusion, rather than as chemical pills, which form the foundation of the pharmaceutical industry. This indicates that there are still unmet clinical needs in drug delivery technology worth addressing.

Skyhawk Therapeutics, Inc. is one of the biotechnology companies aiming to change this situation by developing small-molecule drugs that target RNA to treat diseases. Historically, most drugs targeting RNA were discovered by chance. Skyhawk and its competitors, such as Accent Therapeutics, Arrakis Therapeutics, and Remix Therapeutics, are all focused on related small-molecule drugs. Currently, Skyhawk has gained attention for the rapid progress of its pipeline, thanks to its financing, partnerships, and platform advantages.

Of course, Skyhawk's competing enterprises have not stood still either. Even Ipsen has not put all its eggs in one basket. In 2021, Ipsen established a partnership with Accent Therapeutics to develop a drug for treating acute myeloid leukemia. Meanwhile, Arrakis had already signed agreements with Roche and Amgen earlier, and Remix also reached a collaboration with Johnson & Johnson.