Tolebrutinib

China-based InnoCare could net more than $2 billion biobucks from the deal. Eyeing a drug that it believes holds peak annual sales potential of $12 billion in the U.S. alone, Zenas BioPharma has struck a licensing deal with China-based InnoCare Pharma that could be worth more than $2 billion.The Massachusetts company, which launched just four years ago, is spending up to $100 million upfront and in near-term expected milestone payments to co-develop and possibly commercialize multiple sclerosis (MS) treatment orelabrutinib outside of China and Southeast Asia. The deal also encompasses two autoimmune candidates, which are expected to enter phase 1 testing next year.The agreement also includes 7 million shares of Zenas' common stock, which is usable upon the achievement of another milestone expected early next year. InnoCare could also net more than $2 billion biobucks in regulatory and commercial milestones.On top of that, the 10-year-old Beijing biotech could receive tiered royalties in the high teens on net sales of the products.The prize of the deal is a Bruton’s Tyosine Kinase (BTK) inhibitor called orelabrutinib, an oral treatment which Zenas believes can address compartmentalized inflammation and disease progression in MS.“Preventing disability progression is the highest unmet medical need in multiple sclerosis, a need unfortunately for patients which has been overlooked historically,” Zenas' Chief Scientific Officer, Haley Laken, Ph.D., said in a conference call on Wednesday.A phase 3 trial of orelabrutinib in primary progressive MS (PPMS) is underway, and another phase 3 study of the therapy in secondary progressive MS (SPMS) is expected to kick off in the first quarter of next year. In a phase 2 trial of patients with relapsing-remitting MS (RRMS), orelabrutinib showed significant reductions in inflammatory activity and achieving endpoints that indicate its ability to reduce disease progression.Of MS patients, roughly 20% have SPMS and 10% to 15% have PPMS, Zenas said. Roche’s blockbuster Ocrevus is the only approved therapy for PPMS, but most of its sales are for relapsing MS (RMS) as it is “less impactful at delaying progression in PPMS,” Laken added.As for SPMS, Sanofi’s investigational BTK inhibitor tolebrutinib has scored in a phase 3 trial, showing its ability to slow disease progression, and awaits an FDA decision by the end of this year.“We believe we have a best-in-class product candidate,” Zenas founder and CEO Lonnie Moulder said during the conference call. “While tolebrutinib has a head start, history shows that many blockbuster therapies were not first to market, but succeeded by being differentiated.” Orelabrutinib has been approved in China to treat four types of blood cancer. In the licensing deal, InnoCare did not surrender its rights to orelabrutinib in any oncology indications.“The partnership with (Zenas) represents a significant milestone in our journey, and we will continue to enhance and advance our globalization efforts in the future,” said Jasmine Cui, Ph.D., co-founder and CEO of InnoCare in a release. “We are confident in Zenas’ management team, given their exceptional track record of successful drug development, global regulatory approvals and commercial launches, and their commitment to driving innovation for autoimmune diseases.”Last month, Zenas secured up to $300 million from Royalty Pharma in return for a cut of potential sales of the company’s autoimmune candidate obexelimab, which is in phase 3 testing for IgG4-related disease and systemic lupus erythematosus.   

Zenas BioPharma has now joined nearly three dozen other Western biopharma companies in going to China this year for new assets. The Boston-area drug developer is reviving a BTK inhibitor for multiple sclerosis that once attracted $125 million upfront from Biogen in 2021 but was then culled two years later in a pipeline overhaul as Biogen said it had “ lost its way .” On Wednesday, Zenas said it was stepping in, with the biotech paying up to $100 million in cash in upfront payments and milestones anticipated in 2026 in exchange for certain rights to three assets from InnoCare. Zenas is gaining a Phase 3 BTK inhibitor known as orelabrutinib and two preclinical oral assets expected to enter Phase 1 in 2026: an IL-17AA/AF inhibitor and a brain-penetrant, TYK2 inhibitor. The biotech could fork over a total of $2 billion to its partner in Beijing. To help pay for the upfront and milestones, Zenas simultaneously forged a $120 million private placement. Investors appeared to appreciate the deals, sending Zenas’ stock price $ZBIO up 8% before the opening bell. Its shares had traded relatively nicely, up nearly 15%, since landing on the Nasdaq last September. “This transformative collaboration with InnoCare further positions Zenas to execute on its vision to become a global, fully integrated development and commercial-stage autoimmune-focused biopharmaceutical company,” Zenas founder and CEO Lonnie Moulder said in a press release. Zenas is already in Phase 3 with a former Xencor asset known as obexelimab. The CD-19 x FcγRIIb inhibitor is slated to have topline late-stage results “around year-end ” in immunoglobulin G4-related disease. Zenas will revive the MS efforts for orelabrutinib that Biogen ditched in 2023. In the Wednesday announcement, Moulder said the drug has blockbuster potential, meaning at least $1 billion in peak annual sales. InnoCare is delivering the exclusive rights, outside of Greater China and Southeast Asia, for Zenas to develop, manufacture and market the experimental medicine in MS and non-oncology indications. The Chinese pharma wants to keep the full global rights to cancer indications, though. “Given the statistically significant and clinically meaningful data from the Phase 2 trial, and promising blood-brain barrier penetration capability, orelabrutinib has the potential to transform the treatment paradigm for this devastating disease,” InnoCare co-founder and CEO Jasmine Cui said in the announcement. Orelabrutinib is in a pivotal trial in patients with primary progressive MS, or PPMS. Zenas plans to begin another Phase 3 in patients with secondary progressive MS (SPMS) in the first quarter of 2026. Zenas could run into competition. Sanofi’s BTK inhibitor, the Principia-developed tolebrutinib , is being reviewed by the FDA for non-relapsing SPMS. The approval decision date was pushed back to Dec. 28. The Sanofi drug hasn’t hit the mark in all indications in which it’s been explored. As a part of the Wednesday deal, Zenas also nabs the exclusive rights, again outside of Greater China and Southeast Asia, to the IL-17AA/AF inhibitor. But with the third asset, the TYK2 inhibitor, Zenas gets full rights across the globe. Other brain-penetrant TYK2 inhibitors are in development at drug developers such as Alumis , Biohaven (which also in-licensed its asset from China ), and Sudo Biosciences .