Zenas BioPharma’s Partner, InnoCare Pharma, Announces Achievement of Primary Endpoint in Phase 2b Study of Orelabrutinib, a BTK Inhibitor, for Systemic Lupus Erythematosus

Rhea-AI Summary

Zenas BioPharma (Nasdaq: ZBIO) highlighted that partner InnoCare achieved the primary endpoint in a Phase 2b study of orelabrutinib for Systemic Lupus Erythematosus (SLE) on Dec 15, 2025. In a 187‑patient, randomized (1:1:1) trial, orelabrutinib 75 mg QD produced an SRI‑4 response rate of 57.1% vs 34.4% for placebo at week 48 (p < 0.05). The 75 mg dose showed dose‑dependent benefit versus 50 mg and achieved higher SRI‑6 and BICLA response rates (p < 0.05). Orelabrutinib was reported as well tolerated. Separately, China’s CDE approved a Phase 3 registrational trial in SLE, and Zenas retains commercial/development rights for MS and certain non‑oncology territories per an Oct 2025 license.

Positive

• Primary endpoint met: SRI‑4 57.1% vs 34.4% (p < 0.05) at week 48
• Secondary endpoints met: SRI‑6 and BICLA significantly higher vs placebo (p < 0.05)
• Phase 3 clearance in China: CDE approved Phase 3 registrational trial
• Randomized 187‑patient trial: enrolled and randomized 1:1:1 across two doses and placebo

Negative

• Registrational data pending: Phase 3 results not yet available to confirm durability and safety
• China‑focused Phase 3 approval: CDE approval applies to China; broader global registrational path not specified

Key Figures

Patients enrolled 187 patients Phase 2b SLE trial of orelabrutinib

Randomization ratio 1:1:1 75 mg QD, 50 mg QD, placebo groups

High-dose regimen 75 mg QD Orelabrutinib dosing arm in Phase 2b SLE

Low-dose regimen 50 mg QD Orelabrutinib dosing arm in Phase 2b SLE

SRI-4 response rate 57.1% vs 34.4% Week 48, 75 mg QD vs placebo, primary endpoint

P-value p < 0.05 SRI-4 primary endpoint at week 48

Secondary endpoints SRI-6 & BICLA met Week 48, 75 mg QD vs placebo (p < 0.05)

Study duration 48 weeks Assessment timepoint for primary and key secondary endpoints

Market Reality Check

$40.59 Last Close

Volume Volume 268,262 is slightly below the 20-day average of 299,647 (relative volume 0.9x). normal

Technical Shares at $40.59 are above the $17.32 200-day MA and 2.2% below the $41.50 52-week high.

Peers on Argus 1 Up

Key biotech peers show mixed moves (e.g., AVXL up 9.54%, GERN down 1.45%), while only IMNM appeared on momentum scans, suggesting this ZBIO catalyst is stock-specific rather than a broad sector rotation.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 12	Earnings and update	Positive	+1.7%	Q3 2025 results plus pipeline and financing updates lifted sentiment modestly.
Nov 11	Investor conferences	Positive	+8.4%	Upcoming healthcare conference presentations drove increased investor interest and buying.
Oct 27	Clinical trial data	Positive	+33.1%	Positive Phase 2 MoonStone MS results with strong lesion reduction spurred a sharp rally.
Oct 08	Clinical license deal	Positive	+24.2%	Transformational license for orelabrutinib and two candidates plus financing boosted shares.
Sep 02	Funding agreement	Positive	+9.5%	Up to $300M Royalty Pharma funding for obexelimab development drove a strong move higher.

Pattern Detected

Positive clinical and strategic updates have repeatedly coincided with strong upside reactions, indicating a history of market enthusiasm for ZBIO’s development milestones.

Recent Company History

Over the last six months, ZBIO has reported multiple positive catalysts, including Phase 2 MoonStone success in relapsing MS (news 923355) and a major orelabrutinib license with InnoCare (news 914720). Funding agreements with Royalty Pharma (news 900023) and later Q3 results plus additional financing (news 934337) strengthened the balance sheet. Conference participation (news 933748) kept investor visibility high. The current SLE Phase 2b success for orelabrutinib adds another clinically positive data point on top of this sequence of de‑risking milestones.

Regulatory & Risk Context

Active S-3 Shelf Registration 2025-10-08

$200,000,000 registered capacity

An effective S-3ASR shelf filed on Oct 8, 2025 includes an at‑the‑market program for up to $200,000,000 of common stock, giving ZBIO flexibility to raise equity capital, which could be incrementally dilutive if utilized.

Market Pulse Summary

This announcement highlights that orelabrutinib met its primary SRI-4 endpoint and key secondary SRI-6 and BICLA endpoints at week 48 in a 187‑patient Phase 2b SLE study, with statistical significance at p < 0.05. The data add to ZBIO’s recent stream of positive autoimmune trial results and build on its October 2025 orelabrutinib license. Investors may watch for Phase 3 progress in SLE and MS, additional readouts across the pipeline, and any use of the existing $200,000,000 ATM capacity.

Key Terms

BTK inhibitor medical

"orelabrutinib, a BTK inhibitor, for Systemic Lupus Erythematosus"

A BTK inhibitor is a drug that blocks Bruton's tyrosine kinase, a protein that helps certain immune cells grow and communicate; by interrupting that signal it can reduce harmful immune activity or slow the growth of some blood cancers. For investors, BTK inhibitors matter because their clinical trial results, regulatory approvals, and market uptake can drive large, recurring sales or create competitive advantages for drugmakers, while failures or safety issues can sharply reduce a developer’s value—think of the drug as a targeted tool that can make or break a biotech’s prospects.

Systemic Lupus Erythematosus medical

"in patients with Systemic Lupus Erythematosus (SLE)"

Systemic lupus erythematosus is a chronic autoimmune disease in which the body's immune system mistakenly attacks healthy tissue, causing inflammation that can affect skin, joints, kidneys, heart, lungs and other organs. It matters to investors because disease severity, prevalence, and gaps in effective treatments drive demand for new drugs and diagnostics—think of it as a large, persistent market need where a successful therapy can change patient outcomes and create significant commercial value.

Phase 2b medical

"achievement of the primary endpoint in a Phase 2b study of orelabrutinib"

Phase 2b is a stage in the development of a new medicine or treatment where researchers test its effectiveness and safety in a larger group of people. This step helps determine whether the treatment works well enough to move forward and if it has manageable side effects, which is important for investors because successful results can lead to potential approval and market opportunity.

AI-generated analysis. Not financial advice.

- Orelabrutinib is the first BTK inhibitor to demonstrate significant clinical activity in a Phase 2 clinical trial for SLE -

- Zenas acquired the exclusive right to develop, manufacture and commercialize orelabrutinib in the field of Multiple Sclerosis globally, and non-oncology fields in all territories outside Greater China and Southeast Asia, in October 2025 license agreement with InnoCare –

WALTHAM, Mass., Dec. 15, 2025 (GLOBE NEWSWIRE) -- Zenas BioPharma, Inc. (“Zenas,” “Zenas BioPharma” or the “Company”) (Nasdaq: ZBIO), a clinical-stage global biopharmaceutical company committed to being a leader in the development and commercialization of transformative therapies for patients living with autoimmune diseases, today announced that its partner, InnoCare Pharma (HKEX: 09969; SSE: 688428), announced the achievement of the primary endpoint in a Phase 2b study of orelabrutinib, a potentially best-in-class, highly selective CNS-penetrant, oral, small molecule BTK inhibitor, in patients with Systemic Lupus Erythematosus (SLE). InnoCare also received approval from China’s Center for Drug Evaluation (CDE) to conduct a Phase 3 registrational clinical trial as InnoCare develops orelabrutinib for the treatment of SLE in China.

In the Phase 2b study of orelabrutinib, a total of 187 patients were enrolled and randomized (1:1:1) into three groups: orelabrutinib 75 mg once-daily (QD), orelabrutinib 50 mg QD and placebo. The primary endpoint of the study was the SLE Response Index-4 (SRI-4) response rate at week 48. At week 48, the orelabrutinib 75 mg QD group achieved a statistically significant improvement in SRI-4 response rate compared with placebo (57.1% vs. 34.4%, p < 0.05), meeting the primary endpoint. Additionally, a dose-dependent improvement trend of the orelabrutinib 75 mg QD group compared to the 50 mg QD group was observed.

At week 48, the orelabrutinib 75 mg QD group demonstrated significantly higher SRI-6 and British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response rates compared to the placebo group (p < 0.05), meeting these secondary endpoints.

Orelabrutinib was well tolerated with a safety profile consistent with the mechanism of action of BTK inhibition and the underlying disease biology of SLE.

Results of a previous Phase 2a clinical trial of orelabrutinib for SLE were previously presented as a late breaking oral presentation at the European Union Congress of Rheumatology (EULAR 2022).

In October 2025, Zenas and InnoCare announced a transformational license agreement. Zenas acquired the exclusive right to develop, manufacture and commercialize orelabrutinib in the field of Multiple Sclerosis (MS) globally, and non-oncology fields in all territories outside Greater China and Southeast Asia, while InnoCare retained full global rights in the field of oncology. Zenas also gained the exclusive right to develop, manufacture and commercialize ZB021, an oral, IL-17AA/AF inhibitor in all territories outside Greater China and Southeast Asia, and ZB022, an oral, brain-penetrant, TYK2 inhibitor globally.

About Orelabrutinib
Orelabrutinib is a late-stage, potentially best-in-class, highly selective CNS-penetrant, oral, small molecule Bruton’s Tyrosine Kinase (BTK) inhibitor. In Multiple Sclerosis (MS), Zenas is advancing a Phase 3 trial in Primary Progressive MS (PPMS). A Phase 3 trial in Secondary Progressive MS (SPMS) is expected to initiate in the first quarter of 2026. Orelabrutinib is approved for B cell malignancies in mainland China and Singapore, marketed by our partner InnoCare.

About Zenas BioPharma, Inc.
Zenas is a clinical-stage global biopharmaceutical company committed to becoming a leader in the development and commercialization of transformative therapies for patients living with autoimmune diseases. Our core business strategy combines our experienced leadership team with a disciplined product candidate acquisition approach to identify, acquire and develop product candidates globally that we believe can provide superior clinical benefits to patients living with autoimmune diseases. Zenas is advancing two late-stage, potential franchise molecules, obexelimab and orelabrutinib. Obexelimab, Zenas’ lead product candidate, is a bifunctional monoclonal antibody designed to bind both CD19 and FcγRIIb, which are broadly present across B cell lineage, to inhibit the activity of cells that are implicated in many autoimmune diseases without depleting them. We believe that obexelimab’s unique mechanism of action and self-administered, subcutaneous injection regimen may broadly and effectively address the pathogenic role of B cell lineage in chronic autoimmune disease. Orelabrutinib is a potentially best-in-class, highly selective CNS-penetrant, oral, small molecule BTK inhibitor. Orelabrutinib’s mechanism of action targets pathogenic B cells not only in the periphery but also within the CNS. Additionally, orelabrutinib directly modulates macrophages and microglial cells in the CNS, with the potential to address compartmentalized inflammation and disease progression in MS. Zenas’ earlier stage programs include a potentially best-in-class, oral, IL-17AA/AF inhibitor, and a potentially best-in-class, oral, brain-penetrant, TYK2 inhibitor, both in IND enabling studies. For more information about Zenas BioPharma, please visit https://zenasbio.com/ and follow us on LinkedIn.

Forward looking statements
This press release contains “forward-looking statements” which involve risks, uncertainties and contingencies, many of which are beyond the control of the Company, which may cause actual results, performance, or achievements to differ materially from anticipated results, performance, or achievements. All statements other than statements of historical facts contained in this press release are forward-looking statements. In some cases, forward-looking statements can be identified by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements include, but are not limited to, statements concerning Zenas’ milestones, expectations and intentions, including the potential for obexelimab to become a meaningful therapy across multiple autoimmune diseases and to address the pathogenic role of B cells in autoimmune diseases, the timing of the initiation of, results and data from clinical trials, the timing of initiation of the Phase 3 clinical trial of orelabrutinib in SPMS, the timing to submit an IND and initiate clinical development in ZB021 and ZB022; the potential benefits, development opportunities and commercialization of orelabrutinib and obexelimab; and the expansion of the Zenas pipeline. The forward-looking statements in this press release speak only as of the date of this press release and are subject to a number of known and unknown risks, uncertainties and assumptions that could cause the Company’s actual results to differ materially from those anticipated in the forward-looking statements, including, but not limited to: the Company’s limited operating history, incurrence of substantial losses since the Company’s inception and anticipation of incurring substantial and increasing losses for the foreseeable future; the Company’s need for substantial additional financing to achieve the Company’s goals; the uncertainty of clinical development, which is lengthy and expensive, and characterized by uncertain outcomes, and risks related to additional costs or delays in completing, or failing to complete, the development and commercialization of the Company’s current product candidates or any future product candidates; delays or difficulties in the enrollment and dosing of patients in clinical trials; the impact of any significant adverse events or undesirable side effects caused by the Company’s product candidates; potential competition, including from large and specialty pharmaceutical and biotechnology companies, many of which already have approved therapies in the Company’s current indications; the Company’s ability to realize the benefits of the Company’s current or future collaborations or licensing arrangements and ability to successfully consummate future partnerships; the Company’s ability to obtain regulatory approval to commercialize any product candidate in the United States or any other jurisdiction, the risk that the data from our clinical trials is not sufficient to the satisfaction of the FDA or comparable foreign regulatory authorities to support the submission of a biologics license application or other comparable submission or to obtain regulatory approval for our product candidates for which we seek approval in the U.S. or elsewhere, and the risk that any such approval may be for a more narrow indication than the Company seeks; the Company’s dependence on the services of the Company’s senior management and other clinical and scientific personnel, and the Company’s ability to retain these individuals or recruit additional management or clinical and scientific personnel; the Company’s ability to grow the Company’s organization, and manage the Company’s growth and expansion of the Company’s operations; risks related to the manufacturing of the Company’s product candidates, which is complex, and the risk that the Company’s third-party manufacturers may encounter difficulties in production; the Company’s ability to obtain and maintain sufficient intellectual property protection for the Company’s product candidates or any future product candidates the Company may develop; the Company’s reliance on third parties to conduct the Company’s preclinical studies and clinical trials; the Company’s compliance with the Company’s obligations under the licenses granted to the Company by others, for the rights to develop and commercialize the Company’s product candidates; significant political, trade, regulatory developments, including changes in relations between the U.S. and China; risks related to the operations of the Company’s suppliers, many of which are located outside of the United States, including the Company’s current single source contract manufacturing organizations for drug substance and drug product, WuXi Biologics (Hong Kong) Limited, and InnoCare, both of which are located in China; and other risks and uncertainties described in the section “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2025, as well as other information we file with the Securities and Exchange Commission. The forward-looking statements in this press release are inherently uncertain, speak only as of the date of this press release and may prove incorrect. These statements are based upon information available to the Company as of the date of this press release and while the Company believes such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that the Company has conducted an exhaustive inquiry into, or review of, all potentially available relevant information. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond the Company’s control, these forward-looking statements should not be relied upon as guarantees of future events. The events and circumstances reflected in the forward-looking statements may not be achieved or occur and actual future results, levels of activity, performance and events and circumstances could differ materially from those projected in the forward-looking statements. Moreover, the Company operates in an evolving environment. New risks and uncertainties may emerge from time to time, and management cannot predict all risks and uncertainties. Except as required by applicable law, the Company does not undertake to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

The Zenas BioPharma word mark, logo mark, and the “lightning bolt” design are trademarks of Zenas BioPharma, Inc. or its affiliated companies.

Investor and Media Contact:
Argot Partners
Zenas@argotpartners.com

FAQ

What were the Phase 2b SRI‑4 results for orelabrutinib in SLE announced Dec 15, 2025 for ZBIO?

At week 48 the orelabrutinib 75 mg QD group achieved an SRI‑4 response rate of 57.1% vs 34.4% for placebo (p < 0.05).

Did orelabrutinib meet secondary endpoints in the Phase 2b SLE study reported Dec 15, 2025?

Yes; the 75 mg QD group showed significantly higher SRI‑6 and BICLA response rates versus placebo (p < 0.05).

How many patients were enrolled in the orelabrutinib Phase 2b SLE trial mentioned Dec 15, 2025?

The randomized Phase 2b trial enrolled a total of 187 patients randomized 1:1:1 to two doses and placebo.

What regulatory progress was announced for orelabrutinib on Dec 15, 2025 relevant to ZBIO?

China’s Center for Drug Evaluation granted approval to conduct a Phase 3 registrational trial for orelabrutinib in SLE.

What rights did Zenas (ZBIO) acquire for orelabrutinib in the Oct 2025 license agreement?

Zenas acquired exclusive rights to develop, manufacture and commercialize orelabrutinib in multiple sclerosis globally and non‑oncology fields outside Greater China and Southeast Asia.

Were there safety concerns reported for orelabrutinib in the Phase 2b SLE study announced Dec 15, 2025?

The study reported that orelabrutinib was well tolerated with a safety profile consistent with BTK inhibition and SLE disease biology.