InnoCare and Zenas Announce $2B+ Global Licensing Deal for Three Autoimmune Pipeline Assets

On October 8, InnoCare and Zenas jointly announced that the two parties had reached a blockbuster licensing agreement,Zenas will obtain the global development and commercialization rights for orelabrutinib in the field of multiple sclerosis, as well as the development and commercialization rights for orelabrutinib in other non-oncology therapeutic areas. Zenas also acquires relevant rights to two preclinical molecules: a novel oral IL-17A/F inhibitor and a brain-penetrant oral TYK2 inhibitor.

Under the terms of the agreement, Zenas will pay InnoCare an upfront payment and near-term milestone payments totaling up to $100 million,including milestone payments achieved in 2026, as well as the issuance of 7 million ordinary shares of Zenas to InnoCare, including the shares issued to InnoCare upon achievement of milestones in early 2026, plus other payments for achieving clinical development, regulatory approval, and commercialization milestones,The total transaction amount exceeded $2 billion (approximately RMB 14.2 billion).In addition, InnoCare is entitled to receive tiered royalties of up to the high teens on the annual net sales of the Licensed Products.

Zenas will obtain exclusive global rights to develop, manufacture, and commercialize orelabrutinib for multiple sclerosis, as well as rights to orelabrutinib in non-oncology indications outside of Greater China and Southeast Asia. InnoCare will retain global rights to orelabrutinib in oncology, as well as rights to orelabrutinib in non-oncology indications within Greater China and Southeast Asia. Zenas will also obtain exclusive rights to develop, manufacture, and commercialize an oral IL-17 A/F inhibitor outside of Greater China and Southeast Asia, along with global rights to a brain-penetrant oral TYK2 inhibitor.

Three autoimmune disease pipeline assets are included in this collaboration: orelabrutinib, which is in Phase III clinical trials, and a preclinical oral IL-17 AA/AF inhibitor and an oral TYK2 inhibitor.

Among these, the novel oral IL-17AA/AF inhibitor, which blocks signaling of both the IL-17AA homodimer and the IL-17AF heterodimer, is currently undergoing studies related to its Investigational New Drug (IND) application. Zenas BioPharma expects to submit the IND application and initiate Phase I clinical development in 2026. The brain-penetrant oral TYK2 inhibitor is also undergoing studies related to its IND application, with Zenas BioPharma expecting to submit the IND application and launch Phase I clinical development in 2026.

Of particular note is orelabrutinib, a potential best-in-class, highly selective, orally administered small-molecule BTK inhibitor with strong central nervous system (CNS) penetration, which holds promise for addressing the challenge of disease progression in multiple sclerosis (MS) by isolating inflammation within the CNS.

Previously, in a global Phase II clinical trial involving patients with relapsing-remitting multiple sclerosis (RRMS), orelabrutinib significantly reduced the cumulative number of new gadolinium-enhancing (Gd+) T1 magnetic resonance imaging (MRI) brain lesions at weeks 12 and 24 compared with placebo. It continued to suppress inflammatory activity through week 96 and demonstrated a meaningful impact on endpoints related to disease progression. The safety and tolerability profile of orelabrutinib was consistent with that of other Bruton’s tyrosine kinase (BTK) inhibitors under development for the treatment of multiple sclerosis, and has been well established in multiple prior clinical trials in autoimmune diseases and hematologic malignancies.

Currently, a global, multicenter, randomized, double-blind, placebo-controlled Phase III registrational clinical trial has been initiated to evaluate the safety and efficacy of orelabrutinib at a once-daily (QD) dose of 80 mg in patients with primary progressive multiple sclerosis (PPMS). Zenas plans to launch a second global, multicenter, randomized, double-blind, placebo-controlled Phase III registrational clinical trial of orelabrutinib for the treatment of secondary progressive multiple sclerosis (SPMS) in the first quarter of 2026.

Regarding key assets such as orelabrutinib, InnoCare explicitly stated in its financial report that it is “actively exploring collaboration and licensing opportunities for key assets, with a focus on expanding overseas operations and committed to accelerating global market access for its products through strategic partnerships.”

As early as 2021, InnoCare entered into an overseas licensing deal with Biogen for orelabrutinib.Pursuant to the agreement, InnoCare granted Biogen exclusive global rights to orelabrutinib in the field of multiple sclerosis (MS), as well as exclusive rights in certain autoimmune disease fields outside of China. Under the terms of the agreement, Biogen paid InnoCare a one-time, non-refundable and non-creditable upfront payment of USD 125 million.

However, in 2023, InnoCare and Biogen terminated their global collaboration agreement on orelabrutinib in the field of multiple sclerosis (MS).However, the termination of the collaboration also means that InnoCare will regain all global rights granted to Biogen under the agreement, including relevant intellectual property rights, R&D decision-making authority, manufacturing and commercialization rights, as well as commercial revenues derived from orelabrutinib.

Two years after being shelved by Biogen, orelabrutinib has once again attracted the attention of pharmaceutical companies, with InnoCare successfully reaching a new, more lucrative agreement with Zenas BioPharma. This deal not only completely dispels market skepticism about orelabrutinib but also validates its clinical value and commercial potential as a “potential best-in-class BTK inhibitor with high central nervous system penetration.” InnoCare stated in its announcement that this collaboration represents an “important milestone” in the company’s internationalization strategy.

The other party to this transaction, Zenas BioPharma, is a clinical-stage biopharmaceutical company focused on autoimmune diseases. The company successfully listed on the Nasdaq on September 13, 2024 (stock ticker: ZBIO). Zenas is advancing two late-stage clinical candidates, including orelabrutinib, which is being in-licensed in this transaction, and obexelimab, licensed from Xencor.

Obexelimab is Zenas’ lead candidate, a bifunctional monoclonal antibody that simultaneously binds CD19 and FcγRIIb (widely expressed across the B-cell lineage), thereby inhibiting the activity of cells implicated in many autoimmune diseases without depleting them. The mechanism of action of obexelimab, combined with its self-administered subcutaneous dosing regimen, offers a broad and effective approach to addressing the pathogenic role of the B-cell lineage in chronic autoimmune diseases.

Previously, obexelimab underwent six clinical trials, in which a total of 208 patients received treatment via intravenous infusion or subcutaneous injection. Obexelimab was well tolerated and demonstrated clinical activity in these trials, providing the company with preliminary proof of concept that obexelimab is a B-cell inhibitor effective in treating certain autoimmune diseases.

Currently, Zenas is conducting a Phase III clinical trial for the treatment of IgG4-related disease (IgG4-RD), with patient enrollment completed. The trial aims to evaluate the efficacy and safety of obexelimab in patients with IgG4-RD. INDIGO is the largest clinical trial conducted to date in patients with IgG4-RD. Patient enrollment for the INDIGO trial was completed in November 2024, and Zenas expects to announce the primary data around the end of 2025. In addition, Zenas is conducting Phase II clinical trials for relapsing multiple sclerosis (RMS) and systemic lupus erythematosus (SLE), aiming to assess the efficacy and safety of obexelimab in patients with RMS. Zenas anticipates releasing the trial results in early Q4 2025 and announcing the primary data in mid-2026.

Notably, on the same day the transaction was announced, Zenas BioPharma also announced that it had entered into a securities subscription agreement for a private placement of its common stock, with expected total proceeds of approximately $120 million. Pursuant to the subscription agreement, Zenas will issue approximately 6.3 million shares of common stock upon closing of the private placement, which is expected to occur on or around October 9, 2025.

Following the closing of the private placement, Zenas expects its cash, cash equivalents, and investments to be sufficient to cover operating expenses and capital expenditure requirements through the fourth quarter of 2026. Leveraging this collaboration and financing round, Zenas has not only expanded its product pipeline but also secured ample funding for the commercialization of its first product. The next two years are expected to be a critical period for Zenas’s development.