TYK2 inhibitor( Bristol Myers Squibb)

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 .

Having lost Biogen as a partner a couple of years ago on the oral BTK inhibitor orelabrutinib, InnoCare has now snared another collaborator for its multiple sclerosis (MS) hopeful in the shape of Zenas BioPharma. The deal, announced Wednesday, includes two additional programmes and is potentially worth more than $2 billion. Orelabrutinib is currently being investigated in a Phase III study in patients with primary progressive MS, with Zenas planning a second late-stage trial in patients with secondary progressive MS in the first quarter of 2026. In earlier studies in people with relapsing remitting MS, orelabrutinib demonstrated significant reductions in new gadolinium‐enhancing T1 lesions versus placebo at weeks 12 and 24, with sustained reductions in inflammatory activity through week 96. "With global rights to orelabrutinib, we are advancing a potential blockbuster franchise for progressive MS," remarked Lonnie Moulder, CEO of Zenas, adding, "With its best-in-class potential [it] is strongly positioned to address disease progression independent of relapse activity, the highest unmet medical need in MS." Hope amidst competition With a number of other BTK inhibitors ahead in the race to reach the market for MS — namely Roche's fenebrutinib and Novartis' remibrutinib — an expert interviewed by FirstWord earlier this year suggested that orelabrutinib may still be able to differentiate itself.  "If orelabrutinib is so good at turning off focal inflammatory disease activity, in addition to potentially targeting the mechanisms that underlie progression…then I think you've got something that really makes it a little bit different, and it's easier to use," the expert noted. Along with global development and commercialisation rights to orelabrutinib, excluding its use in oncology, the transaction also gives Zenas rights to an oral, IL-17AA/AF inhibitor and an oral, brain-penetrant, TYK2 inhibitor — both expected to enter clinical development in 2026. "We…expect to have initial patient data from the oral IL-17AA/AF clinical programme in 2027," Moulder said. Under the agreement, Zenas will make upfront and near-term milestone payments of up to $100 million in cash to InnoCare, which will also receive up to 7 million shares of Zenas' stock. The deal includes further development, regulatory and commercial milestones, as well as tiered sales royalties of up to the high teens percentages for all three programmes.Orelabrutinib is approved in China for a number of B-cell malignancies, most recently gaining clearance for the first-line treatment of patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma.