Eli Lilly and Rigel Pharmaceuticals Enter $960 Million Global Licensing Agreement to Co-Develop RIPK1 Inhibitor R552 for Autoimmune and Inflammatory Diseases

Compiled by Fan Dongdong

This Thursday, Eli Lilly announced an exclusive licensing agreement with Rigel Pharmaceuticals. The two companies will jointly develop Rigel’s RIPK1 inhibitor, R552, and will be responsible for the commercialization of this therapy across all indications, including autoimmune and inflammatory diseases.

As part of the transaction, Eli Lilly and Company will obtain the exclusive global license for R552, a receptor-interacting serine/threonine-protein kinase 1 (RIPK1) inhibitor. RIPK1 is a key signaling protein, and scientific studies have confirmed that it can trigger extensive inflammatory cellular processes by inducing cell rupture. R552 is an orally administered, once-daily RIPK1 inhibitor that has previously completed Phase I safety trials in healthy volunteers. In preclinical studies, R552 was shown to prevent joint and skin inflammation in mice.

Following the establishment of the collaboration, the two companies plan to initiate a Phase II clinical trial of an RIPK1 inhibitor this year, with known indications for the trial currently including autoimmune diseases and inflammatory diseases. In addition to Eli Lilly making an upfront payment of $125 million to Rigel, Rigel will be eligible to receive up to $835 million in milestone payments, as well as tiered royalties. Furthermore, Rigel will be eligible to co-commercialize R552 with Eli Lilly in the United States, while Eli Lilly will bear the global commercialization costs for R552.

Rigel Pharmaceuticals has other blood-brain barrier-penetrant RIPK1 inhibitors in its preclinical pipeline, which Eli Lilly may leverage for clinical studies in neurological disorders in the future.

Foreign media believe that Eli Lilly’s move is also aimed at competing with Sanofi, which has also entered the field of RIPK1 inhibitors. As early as 2018, Sanofi partnered with Denali Therapeutics, a biopharmaceutical company focused on developing drugs for neurodegenerative diseases, to co-develop multiple RIPK1 inhibitor molecules for the treatment of a range of neurological and systemic inflammatory diseases, including multiple sclerosis, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), rheumatoid arthritis, and psoriasis. The primary products resulting from this collaboration are DNL747 and DNL758. Notably, the two companies initiated a Phase II clinical trial of DNL758 in cutaneous lupus erythematosus earlier this year.

In addition, the $960 million collaboration with Rigel Pharmaceuticals on a RIPK1 inhibitor will help Eli Lilly further deepen its neuroscience and immunology portfolio. Last December, Eli Lilly reached a $1.04 billion acquisition agreement with Prevail Therapeutics, which is dedicated to developing gene therapies based on adeno-associated virus 9 (AAV9) vectors for patients with neurodegenerative diseases. This acquisition will establish a gene therapy development program within Eli Lilly, building on Prevail’s pipeline, and broaden the therapeutic modalities available for treating hereditary neurodegenerative diseases.

According to Eli Lilly’s 2020 annual report released recently, the company’s total revenue for the year amounted to $24.54 billion, representing a 10% year-over-year increase and exceeding its initial full-year revenue guidance of $23.7 billion to $24.2 billion. For the first time, Eli Lilly also disclosed in its annual report the full-year sales revenue from the China region, which reached $1.117 billion. In addition, Eli Lilly is accelerating its strategic layout in cutting-edge innovative therapies beyond traditional pharmaceuticals. Currently, the company has at least eight candidate drugs in clinical development for neurodegenerative diseases, including donanemab.

However, Eli Lilly and Company’s stock price appeared unaffected by the positive news. As of Thursday’s close, shares of Eli Lilly and Company fell 1.21% to $203.96, while Rigel Pharmaceuticals’ stock rose 14.79% to $5.20.

References:

1.Lilly, Rigel to Partner on RIPK1 Inhibitors in Deal Worth Up to $960 Million

2.Lilly Strikes Licensing Deal With Rigel In Push Toward Neurological, Immunological Therapies

3.Lilly, Rigel Enter Exclusive CNS Development Collaboration

4.Rigel shines with Lilly deal that could hit $960M