A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Obexelimab in Patients With Systemic Lupus Erythematosus - ZB012-02-001

Start Date21 Nov 2024

Sponsor / Collaborator

Zenas BioPharma LLC.

CTIS2024-512707-40-00

/ RecruitingPhase 2

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Obexelimab in Patients with Relapsing Multiple Sclerosis - ZB012-02-002

Start Date07 Nov 2024

Sponsor / Collaborator

Zenas BioPharma LLC.

NCT06559163

/ RecruitingPhase 2

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Obexelimab in Patients With Systemic Lupus Erythematosus

This study aims to examine the efficacy and safety of obexelimab in participants with systemic lupus erythematosus (SLE).

Start Date17 Sep 2024

Sponsor / Collaborator

Zenas BioPharma LLC.

100 Clinical Results associated with Obexelimab

100 Translational Medicine associated with Obexelimab

100 Patents (Medical) associated with Obexelimab

Literatures (Medical) associated with Obexelimab

01 Feb 2025·ADVANCES IN THERAPY

Pharmacokinetics, Pharmacodynamics, Bioavailability, and Immunogenicity of Obexelimab Following Subcutaneous Administration in Healthy Japanese and Non-Japanese Volunteers

Article

Author: Arora, Sujata ; Quinn, Shauna ; Kirk, Rachel ; Gao, Minggeng ; Matijevic, Mark ; Poma, Allen ; Fischer, Tanya ; Wang, Xiaodong

INTRODUCTION:

Obexelimab is an investigational, bifunctional, non-depleting, humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit B cells, plasmablasts, and CD19-expressing plasma cells. In clinical trials, intravenous (IV) administration of obexelimab has been well-tolerated, and demonstrated clinical activity in patients with rheumatoid arthritis, systemic lupus erythematosus, and immunoglobulin G4-related disease. This study was performed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of obexelimab following subcutaneous (SC) administration, and compare PK/PD profiles between healthy Japanese and non-Japanese volunteers.

METHODS:

This was a Phase I, open-label, parallel group, multiple-dose study. Participants were randomized to five cohorts to receive three doses of obexelimab as 125 mg SC every 14 days (q14d), 250 mg SC q14d, 375 mg SC q14d, 250 mg IV q14d, and 125 mg SC every 7 days, then monitored during a 28-day safety follow-up period. PK/PD assessments were performed after the first and third doses.

RESULTS:

A total of 50 healthy volunteers (25 Japanese and 25 non-Japanese) were enrolled and distributed evenly between dose cohorts. All SC dosing regimens were well-tolerated. Dose-proportional PK was observed following SC doses with a bioavailability of approximately 60%. No clinically meaningful differences in PK parameters were found between healthy Japanese and non-Japanese participants. Antidrug antibodies (ADA) were detected in 6/50 (12%) participants after dosing. ADA had no or minimal impact on PK in all six ADA positive participants. Near-complete CD19 receptor occupancy and an absolute B-cell count nadir of approximately 50% baseline levels were maintained for the duration of the study in both populations.

CONCLUSION:

Obexelimab SC administration demonstrated favorable bioavailability, was well-tolerated, and showed no clinically meaningful ethnic differences in PK/PD. These results support further clinical development of SC obexelimab to treat B-cell mediated autoimmune diseases.

TRIAL REGISTRATION:

NCT02867098.

02 Dec 2023·Expert opinion on biological therapy

Antibody based therapeutics for autoimmune hemolytic anemia

Review

Author: Fattizzo, Bruno ; Cavallaro, Francesca ; Barcellini, Wilma

INTRODUCTION:

Autoimmune hemolytic anemia (AIHA) treatment has been revolutionized by the introduction of target therapies, mainly monoclonal antibodies (MoAbs).

AREAS COVERED:

The anti-CD20 rituximab, which targets Ab production by B-cells, induces 80% of response in warm-type AIHA (wAIHA) and 50-60% in cold agglutinin disease (CAD). Other B-cell targeting MoAbs including ianalumab, povetacicept, and obexelimab are under active study. The anti-CD38 MoAb daratumumab has been used in several reports to target long-lived plasma-cells responsible for AIHA relapse, being effective even in multi-refractory cases. Anti-complement MoAbs will soon change the treatment paradigm in CAD; the anti-C1s sutimlimab rapidly increased Hb in more than 80% of the cases. Finally, MoAbs inhibiting the neonatal Fc receptor (FcRn), such as nipocalimab, can reduce the half-life of the pathogenic autoAbs, representing a promising treatment for wAIHA.

EXPERT OPINION:

MoAbs offer the potential to improve efficacy by reducing toxicity. However, there is a huge need for clinical trials exploring response duration rather than short-term efficacy. Complement inhibitors and anti-FcRns do not abrogate autoAb production and are being developed as long-term therapies. Thus, the combination of B-cell/plasma cell targeting drugs deserves to be explored. On the other hand, their rapid efficacy should be exploited for the acute AIHA phase.

01 Dec 2023·Arthritis & rheumatology (Hoboken, N.J.)

Obexelimab in Systemic Lupus Erythematosus With Exploration of Response Based on Gene Pathway Co‐Expression Patterns: A Double‐Blind, Randomized, Placebo‐Controlled, Phase 2 Trial

Article

Author: Khosroshahi, Arezou ; James, Judith A ; Rathi, Gaurav ; Koumpouras, Fotios ; Askanase, Anca ; Arora, Sujata ; Guthridge, Joel ; Matijevic, Mark ; Merrill, Joan T ; June, Joshua ; Burington, Bart ; Zack, Debra J ; Wax, Stephen ; Foster, Paul ; Smith, Miles ; Machua, Wambui ; Wang, Xiaodong ; Gao, Minggeng ; Sheikh, Saira Z

Objective:

Obexelimab is an investigational, bifunctional, noncytolytic monoclonal antibody that binds CD19 and FcyRIIb to inhibit B cells, plasmablasts, and plasma cells. This trial evaluated the efficacy and safety of obexelimab in the treatment of patients with systemic lupus erythematosus (SLE).

Methods:

During screening, patients with active, non–organ‐threatening SLE received corticosteroid injections to ameliorate symptoms while immunosuppressants were withdrawn (≤10 mg/day prednisone equivalent and ≤400 mg/day hydroxychloroquine allowed). Patients with improved disease activity were randomized 1:1 to obexelimab 5 mg/kg intravenously or placebo once every 2 weeks until week 32 or loss of improvement (LOI).

Results:

In this study, 104 patients were randomized. Analysis of the primary endpoint, proportion of patients reaching week 32 without LOI, used an efficacy‐evaluable (EE) population defined as patients who completed the study or withdrew for flare or treatment‐related toxicity. This endpoint did not reach statistical significance: 21 of 50 obexelimab‐treated patients (42.0%) versus 12 of 42 patients (28.6%) treated with a placebo (P = 0.183). Time to LOI was increased in obexelimab‐treated patients versus patients treated with a placebo in the EE (hazard ratio [HR] 0.53, P = 0.025) and intention‐to‐treat (HR 0.59, P = 0.062) populations. In obexelimab‐treated patients, B cells decreased approximately 50%, and trough concentration and inclusion in baseline gene expression clusters with high B cell pathway modules were associated with increased time to LOI. Obexelimab was associated with infusion reactions but was generally safe and well‐tolerated.

Conclusion:

Although the primary endpoint was not reached, secondary analysis showed time to LOI was significantly increased in obexelimab‐treated patients, and analysis of patient subsets defined by gene expression patterns at baseline suggests a responding subpopulation.image

News (Medical) associated with Obexelimab

15 May 2025

·www.globenewswire.com

Zenas BioPharma Reports First Quarter 2025 Financial Results and Provides Corporate Updates

- Topline results from pivotal Phase 3 INDIGO trial in Immunoglobulin G4-Related Disease expected around year-end 2025 - - Phase 2 MoonStone trial in Relapsing Multiple Sclerosis enrollment concluding; topline results expected early in the fourth quarter 2025 - - Enrollment of Phase 2 SunStone trial in Systemic Lupus Erythematosus expected to be completed by year-end 2025; topline results expected mid-2026 - - Strengthened leadership team with appointments of Lisa von Moltke, M.D., Head of Research and Development and Chief Medical Officer, and Haley Laken, Ph.D., Chief Scientific Officer - - Cash, cash equivalents and investments of $314.2 million as of March 31, 2025, expected to provide financial runway into the fourth quarter of 2026 - WALTHAM, Mass., May 15, 2025 (GLOBE NEWSWIRE) -- Zenas BioPharma, Inc. (“Zenas” or the “Company”) (Nasdaq: ZBIO), a clinical-stage global biopharmaceutical company committed to being a leader in the development and commercialization of therapies for autoimmune diseases, today reported financial results for the first quarter ended March 31, 2025, and provided recent corporate updates. “We are pleased with the continued momentum of our obexelimab program across ongoing Phase 2 and Phase 3 clinical trials, for which we expect to report topline results later this year from trials in patients with relapsing multiple sclerosis and IgG4-RD,” said Lonnie Moulder, Founder and Chief Executive Officer of Zenas. “With a strengthened team following the recent additions of Lisa and Haley, we are well positioned to execute on our clinical trials and advance obexelimab as a differentiated B cell inhibitor with a potentially safer, more potent and convenient profile for patients.” Recent corporate highlights Obexelimab, a CD-19 x FcγRIIb inhibitor of B cell function Immunoglobulin G4-Related Disease (IgG4-RD): Advanced the Phase 3 INDIGO trial, a global registration-directed, multicenter, randomized, double-blind, placebo-controlled trial, to evaluate the efficacy and safety of obexelimab in patients with IgG4-RD. INDIGO is the largest clinical trial conducted in patients living with IgG4-RD to date. In the fourth quarter of 2024, Zenas completed the target enrollment of the INDIGO trial and expects to report topline results from the INDIGO trial around year-end 2025.Relapsing Multiple Sclerosis (RMS): Patient screening concluding with the final subject expected to be enrolled in early-June in the Phase 2 MoonStone trial, a multicenter, randomized, double-blind, placebo-controlled trial, to evaluate the efficacy and safety of obexelimab in patients with RMS. The Company expects to report topline results from this trial, including the 12-week primary endpoint results, early in the fourth quarter of 2025.Systemic Lupus Erythematosus (SLE): Continued enrolling in the Phase 2 SunStone trial, a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of obexelimab in patients with SLE. Zenas expects to complete enrollment in this trial by year-end 2025 and report topline results in mid-2026. Other corporate highlights Beyond progress with obexelimab, during the first quarter and more recently, the Company: Strengthened its leadership team by appointing Lisa von Moltke, M.D., as Head of Research and Development and Chief Medical Officer, and Haley Laken, Ph.D., as Chief Scientific Officer. Dr. von Moltke brings over 30 years of U.S. and international drug development experience spanning multiple therapeutic areas, including autoimmune diseases, early- and late-stage clinical development, and commercialization at large and emerging growth companies. Dr. Laken brings over 25 years of leadership experience in research, development operations, research and development strategy and business development.Out-licensed regional rights to its thyroid eye disease program, including ZB001, an insulin-like growth factor-1 receptor (anti-IGF-1R) monoclonal antibody, to Zai Lab (Zai). Zenas received an upfront payment and is eligible to receive milestone payments and royalties in the future, as consideration for an exclusive sublicense to Zai to develop and commercialize ZB001 and related programs in Greater China. First quarter 2025 financial results As of March 31, 2025, the Company’s cash, cash equivalents and investments was $314.2 million. The Company expects that its cash, cash equivalents and investments, as of March 31, 2025, will fund its operating expenses and capital expenditure requirements into the fourth quarter of 2026.License and collaboration revenue was $10.0 million for the quarter ended March 31, 2025, related to the one-time non-refundable upfront cash payment received in connection with the sublicense agreement with Zai. The Company did not recognize any license and collaboration revenue during the quarter ended March 31, 2024.Research and development (R&D) expenses were $34.9 million for the quarter ended March 31, 2025, compared to $22.6 million for the quarter ended March 31, 2024. The increase of $12.3 million in R&D expenses primarily relates to an increase in costs related to the clinical development and manufacturing of obexelimab.General and administrative (G&A) expenses were $12.4 million for the quarter ended March 31, 2025, compared to $4.9 million for the quarter ended March 31, 2024. The increase of $7.5 million in G&A expenses was due to an increase in personnel costs, including stock-based compensation expenses, pre-commercialization activities including hiring and other expenses including costs associated with operating as a public company.Net loss was $33.6 million for the quarter ended March 31, 2025, compared to net loss of $27.8 million for the quarter ended March 31, 2024. About ObexelimabObexelimab 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. This 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. Obexelimab has been evaluated in five completed clinical trials in a total of 198 patients who received obexelimab either as an intravenous infusion or as a subcutaneous injection. Obexelimab was well tolerated and demonstrated clinical activity across these five clinical trials, providing the Company an initial clinical proof of concept for obexelimab as a potent B cell inhibitor for the treatment of patients living with certain autoimmune diseases. Currently, Zenas is conducting multiple Phase 2 and Phase 3 trials of obexelimab in several autoimmune diseases including Immunoglobulin G4-Related Disease, Relapsing Multiple Sclerosis and Systemic Lupus Erythematosus. 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 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’ lead product candidate, obexelimab, 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. For more information about Zenas BioPharma, please visit www.zenasbio.com and follow us on LinkedIn. Forward looking statementsThis 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 the timing and results of ongoing and future clinical trials, including expectations on the timing of reporting INDIGO trial topline results, the last patient to be enrolled in and the 12-week primary endpoint data for the MoonStone trial and the anticipated timing of completing enrollment and reporting topline results for the SunStone trial; its growth strategy; and cash runway guidance. 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, 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 sole contract manufacturing organization for drug substance and drug product, WuXi Biologics (Hong Kong) Limited, which is 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 March 31, 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. Zenas BioPharma, Inc.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(in thousands except share and per share amounts)Unaudited Three Months Ended March 31, 2025 2024 Revenue: License and collaboration revenue $10,000 $— Total revenue 10,000 — Operating expenses: Research and development 34,915 22,645 General and administrative 12,415 4,933 Total operating expenses 47,330 27,578 Loss from operations (37,330) (27,578)Other income (expense), net: Other income (expense), net 3,552 (222)Total other income (expense), net 3,552 (222)Income tax benefit 205 — Net loss to common stockholders $(33,573) $(27,800)Net loss per share attributable to common stockholders - basic and diluted $(0.80) $(17.89)Weighted-average common stock outstanding - basic and diluted 41,800,802 1,554,087 Zenas BioPharma, Inc.SELECTED CONSOLIDATED BALANCE SHEET DATA(in thousands)Unaudited March 31, 2025Cash, cash equivalents and investments $314,214 Working capital 268,675 Total assets 333,766 Accumulated deficit (420,964)Total stockholders’ equity 284,317 Investor and Media Contact:Argot PartnersZenas@argotpartners.com

Phase 2Phase 3Financial StatementExecutive ChangePhase 1

14 Apr 2025

·www.prnewswire.com

FDA Approval of Amgen's UPLIZNA for IgG4-related Disease Opens New Market Opportunity in Rare Autoimmune Segment | DelveInsight

With UPLIZNA receiving a label expansion that opens the door to a previously untapped rare disease market, Amgen is seeing strong returns on its USD 27.8 billion acquisition of Horizon Therapeutics. The drug has become the first to receive FDA approval specifically for treating immunoglobulin G4-related disease (IgG4-RD). LAS VEGAS, April 14, 2025 /PRNewswire/ -- IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition marked by the accumulation of IgG4-positive plasma cells in affected tissues, sometimes accompanied by elevated blood levels of IgG4. The disease can impact nearly any organ, with common sites including the pancreas, bile ducts, salivary and lacrimal glands, orbits, kidneys, lungs, and the retroperitoneal space. Due to its relatively recent identification, lack of widespread clinical awareness, and often subtle or slow-developing symptoms, IgG4-RD is likely underdiagnosed and underreported. It occurs more frequently in men, with most diagnoses in adults between their 30s and 50s, though cases have also been documented in children. In 2024, there were ~ 149K diagnosed prevalent cases of IgG4-RD across the 7MM, with the United States representing the largest share of these cases. In patients with IgG4-related disease, treatment may not always be necessary. In cases where individuals are asymptomatic, a watchful waiting approach can be appropriate. However, when vital organs are involved or symptoms are present, timely treatment becomes crucial, as IgG4-RD can lead to significant organ damage and dysfunction. Glucocorticoids are considered the first-line treatment, as outlined in the International Consensus Statement on IgG4-RD management. They typically produce rapid and substantial clinical improvement in both pancreatic and extra-pancreatic manifestations. To help maintain remission and reduce long-term steroid use, various glucocorticoid-sparing agents—such as azathioprine, mycophenolate mofetil, methotrexate, cyclophosphamide, and bortezomib—have been utilized across different organ systems, though their effectiveness varies. Steroid-sparing drugs like azathioprine, mycophenolate mofetil, and methotrexate are used to minimize the side effects of prolonged steroid therapy and support long-term disease control. However, the evidence supporting their efficacy remains limited. Rituximab has emerged as a promising newer option; it targets CD20-positive plasmablast precursors, leading to a reduction in plasmablasts and a subsequent decline in IgG4 production. To know more about IgG4-RD treatment options, visit @ New Treatment for IgG4-related Disease Recently, in April 2025, the FDA approved Amgen's anti-CD19 therapy, UPLIZNA, for the treatment of IgG4-related disease, making it the first and only approved treatment specifically for this condition, according to the company's announcement. This label expansion is supported by data from the Phase III MITIGATE trial, initially presented by Amgen in November 2024. The study showed that UPLIZNA reduced the risk of disease-related flares by 87% compared to placebo. Over the 52-week study period, only 7 out of 68 patients receiving UPLIZNA experienced flares, compared to 40 out of 67 in the placebo group—a difference Amgen highlighted as statistically significant. Additionally, 57.4% of patients treated with UPLIZNA achieved complete remission at the one-year mark versus just 22.4% of those on placebo. Nearly 90% of patients in the UPLIZNA arm were able to stop using glucocorticoids, compared to 37.3% in the placebo group. Within just 8 weeks of treatment, UPLIZNA recipients had a tenfold reduction in total glucocorticoid usage compared to placebo. Administered via intravenous infusion, UPLIZNA is a humanized monoclonal antibody that targets the CD19 protein found on specific immune cells. By binding to CD19, it depletes both immature and mature B cells, thereby addressing a key disease mechanism in IgG4-RD, which involves the widespread infiltration of B cells into affected tissues, leading to organ damage. Amgen recorded USD 379 million in UPLIZNA sales in 2024 from its original indication alone. However, the recent approval for IgG4-related disease presents a significant growth opportunity, as this new market includes a treatable patient population that is roughly twice as large as that for NMOSD. Learn more about the FDA-approved IgG4-RD drugs @ Drugs for IgG4-related Disease Treatment Apart from Amgen, key players such as Zenas Biopharma, Bristol Myers Squibb and Sanofi are also evaluating their lead candidates in different stages of clinical development, respectively. They aim to investigate their products to treat IgG4-RD. The treatment pipeline for IgG4-RD includes several promising therapies in advanced stages of development, such as ZB012 (obexelimab) and Rilzabrutinib, among others. These emerging treatments hold the potential to significantly improve patient outcomes and address existing gaps in care. Discover which therapies are expected to grab major IgG4-RD market share @ IgG4-related Disease Market Report Obexelimab (XmAb5871) is a dual-function monoclonal antibody that targets both CD19 and FcγRIIb—proteins found widely on B cells—aiming to suppress B-cell activity involved in various autoimmune disorders without destroying the cells. Its distinctive mechanism and subcutaneous self-injection format position it as a promising therapy to effectively address the role of B cells in chronic autoimmune conditions. Zenas is currently advancing obexelimab through multiple Phase II and III clinical trials for a range of autoimmune diseases, including IgG4-related disease, multiple sclerosis, systemic lupus erythematosus, and warm autoimmune hemolytic anemia. In August 2023, The Lancet Rheumatology published Phase II trial results showing its potential in treating IgG4-RD. These findings have led to an ongoing Phase III trial focused on evaluating the safety and efficacy of obexelimab via subcutaneous injection in patients with IgG4-RD. Rilzabrutinib (also known as PRN1008) is a selective, orally available, reversible covalent inhibitor of Bruton's Tyrosine Kinase (BTK), exhibiting a potent IC50 of 1.3 nM. It targets a cysteine residue on BTK, resulting in a slow dissociation rate—about 79% of BTK binding remains in peripheral blood mononuclear cells (PBMCs) 18 hours after the compound is washed out in vitro. This covalent binding is fully reversible upon denaturation of the protein. Functionally, rilzabrutinib suppresses anti-IgM-induced human B-cell proliferation and inhibits CD69 expression on B cells, with IC50 values of 5 ± 2.4 nM and 123 ± 38 nM, respectively, under 10% serum conditions. In August 2020, Sanofi entered into a definitive agreement to acquire Principia Biopharma, a deal approved unanimously by both companies' boards. The acquisition strengthened Sanofi's pipeline in immunology by integrating Principia's BTK inhibitors—including rilzabrutinib—into its broader strategy to develop next-generation therapies for autoimmune diseases. Discover more about drugs for IgG4-RD in development @ IgG4-related Disease Clinical Trials The anticipated launch of these emerging therapies for IgG4-RD are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the IgG4-RD market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for IgG4-RD is expected to grow from USD 170 million in 2024, with a significant CAGR by 2034. This growth can be attributed to the approval of new therapies with improved safety and tolerability, which will significantly impact the treatment landscape in the coming years. DelveInsight's latest published market report, titled as IgG4-related Disease Market Insight, Epidemiology, and Market Forecast – 2034 , will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the IgG4-RD country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The IgG4-RD market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent Cases of IgG4-RD Gender-specific Diagnosed Prevalent Cases of IgG4-RD Age-specific Diagnosed Prevalent Cases of IgG4-RD The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM IgG4-RD market. Highlights include: 10-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this IgG4-RD market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the IgG4-RD market. Also, stay abreast of the mitigating factors to improve your market position in the IgG4-RD therapeutic space. Related Reports IgG4-related Disease Epidemiology IgG4-related Disease Epidemiology Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted IgG4-RD epidemiology in the 7MM, i.e., the United States, EU4 (Germany, Spain, Italy, and France), the United Kingdom, and Japan. IgG4-related Disease Pipeline IgG4-related Disease Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key IgG4-RD companies, including Amgen, Sanofi, Zenas Biopharma, Bristol-Myers Squibb, among others. Warm Autoimmune Hemolytic Anemia Market Warm Autoimmune Hemolytic Anemia Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key wAIHA companies including ZENAS BIOPHARMA, JOHNSON & JOHNSON INNOVATIVE MEDICINE, NOVARTIS, MORPHOSYS, SANOFI, ALPINE IMMUNE SCIENCES , among others. Neuromyelitis Optica Market Neuromyelitis Optica Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key neuromyelitis optica companies including Alexion Pharmaceutical, AstraZeneca , among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultDrug ApprovalPhase 2Phase 3Acquisition

11 Feb 2025

·www.globenewswire.com

Zenas BioPharma Announces Key 2024 Accomplishments and 2025 Business Objectives to Support the Global Development and Commercialization of Therapies for Autoimmune Diseases

- Advancing Phase 2 and Phase 3 trials of obexelimab, a unique CD-19 x FcγRIIb inhibitor of B cell function- -Topline results from Phase 2 Trial in Relapsing Multiple Sclerosis (MoonStone) expected in third quarter 2025- -Topline results from pivotal Phase 3 Trial in Immunoglobulin G4-Related Disease (INDIGO) expected year-end 2025- - Enrollment of Phase 2 Trial in Systemic Lupus Erythematosus (SunStone) expected to be completed in 2025- - Out-licensed greater-China anti-IGF-1R Thyroid Eye Disease programs to Zai Lab - Feb. 05, 2025 -- Zenas BioPharma, Inc. (“Zenas” or the “Company”) (Nasdaq: ZBIO), a clinical-stage global biopharmaceutical company committed to being a leader in the development and commercialization of therapies for autoimmune diseases, today announced its 2024 accomplishments, outlined its key business objectives for 2025 and announced preliminary unaudited cash balance as of year-end 2024. “Based upon the progress achieved across all of our corporate goals and objectives during 2024, we enter 2025 with an opportunity to achieve major value-driving milestones with the anticipated results from our ongoing obexelimab Phase 2 and Phase 3 clinical trials,” said Lonnie Moulder, Founder and Chief Executive Officer of Zenas. “We are extremely proud of the accomplishments of our dedicated team as we enter the year well-financed and able to focus on execution, and achievement of our key objectives for the year.” The Company enters 2025 well-capitalized to deliver its key milestones with approximately $350 million in cash, cash equivalents, and short-term investments as of December 31, 2024, 1 which is expected to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2026. During 2024, the Company achieved the following objectives and announced a recent business development transaction: Completed enrollment of the Phase 3 INDIGO trial, a global Phase 3 registration-directed, randomized, double-blind placebo-controlled trial of obexelimab in patients with Immunoglobulin-G4 Related Disease (IgG4-RD), the largest clinical trial ever conducted in this patient population. Initiated the Phase 2 MoonStone trial, a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial, to evaluate the efficacy and safety of obexelimab in patients with Relapsing Multiple Sclerosis (RMS). Initiated the Phase 2 SunStone trial, a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial, to evaluate the efficacy and safety of obexelimab to reduce disease activity in patients with Systemic Lupus Erythematosus (SLE). Provided initial data from the Phase 2 SApHiAre trial, a global, multicenter, open-label safety and dose confirmation run-in period (SRP) to evaluate the safety and activity of obexelimab in patients with warm Autoimmune Hemolytic Anemia (wAIHA). Obexelimab achieved clinical proof-of-mechanism by increasing hemoglobin levels and red blood cells, and decreasing LDH and total bilirubin levels. Obexelimab was well tolerated in the SRP. Completed an upsized Series C and initial public offering, raising approximately $458.7 million in aggregate gross proceeds to fund its planned activities for obexelimab and the Company’s growth strategy. Bolstered its leadership team with the appointments of Chief Commercial Officer, Orlando Oliveira, and Chief Legal Officer, Jeff Held. Out-licensed ZB005, a human IgG4 monoclonal antibody designed to bind only to the active form of C1s, for which Zenas held the development and commercialization rights in China, Hong Kong, Macau and Taiwan (Greater China) through an exclusive license with Dianthus. The Company recently out-licensed regional rights to its thyroid eye disease programs, including ZB001, an insulin-like growth factor-1 receptor (anti-IGF-1R) monoclonal antibody, to Zai Lab (Zai). Zenas received an upfront fee and is eligible to receive milestone payments and royalties in the future, as consideration for an exclusive sublicense to Zai to develop and commercialize ZB001 and related programs in Greater China. Obexelimab 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. This unique mechanism of action and self-administered, subcutaneous once-weekly injection regimen may broadly and effectively address the pathogenic role of B cell lineage in chronic autoimmune disease. Obexelimab has been evaluated in five completed clinical trials in a total of 198 patients who received obexelimab either as an intravenous infusion or as a subcutaneous injection. Obexelimab was well tolerated and demonstrated clinical activity across these five clinical trials, providing the Company an initial clinical proof of concept for obexelimab as a potent B cell inhibitor for the treatment of patients living with certain autoimmune diseases. During 2025, the Company expects to achieve the following key clinical milestones: Report the 12-week primary endpoint results in the third quarter of 2025 from the Phase 2 MoonStone trial in patients with RMS. The role of B cells in the pathogenesis of multiple sclerosis including RMS has been demonstrated through the successful clinical development, approval and clinical use of anti-CD20 B cell targeting therapies of other companies, including OCREVUS® (ocrelizumab) and KESIMPTA® (ofatumumab), which selectively deplete CD20-expressing B cells. The Company believes obexelimab’s unique mechanism of action to potently inhibit but not deplete a broader B cell lineage than CD20, nonclinical data, and a subcutaneous injection regimen, supports its potential for the treatment of RMS. Following an initial screening period, patients in the MoonStone trial are being randomized 2:1 to 250 mg of obexelimab or placebo administered as a subcutaneous injection every seven days for a 12-week treatment period. The primary objective of this double-blinded portion of the trial will be to assess the change from baseline in the cumulative number of gadolinium (Gd) enhancing lesions identified on T1-weighted magnetic resonance imaging (MRI). Upon completion of the 12-week period, patients will enter an open-label period where patients on placebo will receive obexelimab treatment for at least three months, and patients initially randomized to obexelimab will continue treatment. Important secondary endpoints during this open-label period include using standardized assessments, novel 3D imaging and biomarkers, including serum neurofilament light chain (NfL), to evaluate the impact of obexelimab on disease progression. More information on the Phase 2 MoonStone trial (NCT06564311) is available at clinicaltrials.gov Report topline results year-end 2025 from the Phase 3 INDIGO trial in patients with IgG4-RD. IgG4-RD is a chronic fibro-inflammatory disease that can affect virtually all organ systems, including the pancreas, biliary tract, salivary and lacrimal glands, lungs, and kidneys. Patients with IgG4-RD may present with a single organ involved but more frequently present with multiple organ involvement. As the disease progresses and patients experience new or worsening symptoms (i.e., flares), lesions develop in additional organs and the cellular inflammation characterizing early disease moves toward a more fibrotic stage, which can lead to major irreversible tissue damage and ultimately organ failure. We estimate that the currently diagnosed population of IgG4-RD patients in the U.S. is approximately 20,000, with comparable prevalence rates globally. Despite the growing recognition of IgG4-RD and advances in the understanding of its pathophysiology, there are no approved therapies for the treatment of this disease and there remains high unmet medical need. The current standard of care is treatment with glucocorticoids (GCs). Although GCs are initially effective, treatment with GCs can often result in various complications and co-morbidities. Most patients can relapse within 12 months of discontinuing GC treatment, and maintenance therapy with GCs has not been shown to prevent recurrence of disease. The pathogenesis of IgG4-RD suggests that B cell-targeted therapies may provide therapeutic benefit. Although not approved by any regulatory authorities to treat IgG4-RD, certain B cell depleting agents (e.g., rituximab) are occasionally administered to patients with IgG4-RD. However, B cell depleting agents are often associated with infections, including serious opportunistic infections, and can compromise a patient’s ability to mount a response to vaccinations. The reported evidence for the role of B cells in the pathogenesis of IgG4-RD, the observed effects of B cell targeting agents in previous trials in IgG4-RD, the data from our Phase 2 IgG4-RD trials with obexelimab, and its unique, non-depleting mechanism and once-weekly, subcutaneous injection regimen support its development in patients with IgG4-RD. INDIGO is the largest clinical trial conducted in patients living with IgG4-RD and is designed to evaluate the safety and efficacy of obexelimab in approximately 190 patients with active IgG4-RD and being conducted at approximately 100 sites in 20 countries. Following an initial screening period, patients were randomized 1:1 to 250 mg of obexelimab or placebo administered as a subcutaneous injection every seven days for 52 weeks, followed by an opportunity for eligible patients to continue in an open-label extension period where all patients will receive treatment with obexelimab. The primary efficacy endpoint of INDIGO is the time to first IgG4-RD flare, as determined per protocol by the investigator and the adjudication committee. Secondary endpoints include annualized flare rate, the proportion of patients achieving complete remission, and use and quantity of rescue medication, including GCs. More information on the Phase 3 INDIGO trial (NCT05662241) is available at clinicaltrials.gov Complete enrollment in 2025 in the Phase 2 SunStone trial in patients with SLE and report topline results in the first half of 2026. The crucial role of B cells in SLE pathogenesis is well recognized, from producing autoantibodies to abnormal regulation of immune responses. Moreover, SLE is an autoimmune disease characterized by B cell dysfunction, the production of autoantibodies toward cellular and nuclear components, and multiorgan damage caused by immune complex deposition and inflammation within affected tissues. Current treatments are limited in number and modestly effective. Obexelimab has demonstrated clinical activity in a prior Phase 2 double-blind, randomized trial demonstrating proof-of-concept in the overall trial population and increased response in patients who maintained higher systemic exposure to obexelimab, and also in biomarker-defined subpopulations. Coupled with the safety data obtained to date, we believe these data provide support for the development of obexelimab in patients with SLE. Patients with active SLE determined at screening by the investigator and adjudication committee are randomized 1:1 to obexelimab 250 mg or placebo administered as a subcutaneous injection every seven days for 24 weeks. The 250 mg once-weekly subcutaneous injection dose has been selected to maximize the potential for clinical activity as higher systemic exposure (Ctrough) correlated with greater clinical activity in the prior Phase 2 trial in SLE. The primary endpoint is the percentage of responders, defined by BILAG-based Composite Lupus Assessment, with a reduction of SLE disease activity at week 24. Biomarker analysis is planned to be conducted in all patients, including baseline RNA expression profiles to immunophenotype patients and evaluation of their differential responses to treatment. More information on the Phase 2 SunStone trial (NCT06559163) is available at clinicaltrials.gov Zenas is a clinical-stage global biopharmaceutical company committed to becoming a leader in the development and commercialization of transformative therapies for patients 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’ lead product candidate, obexelimab, 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. For more information about Zenas BioPharma, please visit www.zenasbio.com and follow us on LinkedIn. 1 This amount is preliminary and unaudited and is subject to completion of the Company’s financial closing procedures. As a result, this amount may differ materially from the amount that will be reflected in the Company’s consolidated financial statements for the year ended December 31, 2024. The content above comes from the network. if any infringement, please contact us to modify.

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Indication	Highest Phase	Country/Location	Organization	Date
Warm autoimmune hemolytic anemia	Phase 3	Italy	Zenas BioPharma LLC.	25 Sep 2023
Warm autoimmune hemolytic anemia	Phase 3	Poland	Zenas BioPharma LLC.	25 Sep 2023
Warm autoimmune hemolytic anemia	Phase 3	Spain	Zenas BioPharma LLC.	25 Sep 2023
Warm autoimmune hemolytic anemia	Phase 3	Taiwan Province	Zenas BioPharma LLC.	25 Sep 2023
Warm autoimmune hemolytic anemia	Phase 3	United Kingdom	Zenas BioPharma LLC.	25 Sep 2023
Immunoglobulin G4-Related Disease	Phase 3	United States	Zenas BioPharma LLC.	30 Sep 2022
Immunoglobulin G4-Related Disease	Phase 3	China	Zenas BioPharma LLC.	30 Sep 2022
Immunoglobulin G4-Related Disease	Phase 3	Japan	Zenas BioPharma LLC.	30 Sep 2022
Immunoglobulin G4-Related Disease	Phase 3	Argentina	Zenas BioPharma LLC.	30 Sep 2022
Immunoglobulin G4-Related Disease	Phase 3	Canada	Zenas BioPharma LLC.	30 Sep 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02725476 (Pubmed \| Lancet Rheumatol)	Phase 2	Immunoglobulin G4-Related Disease	15	Obexelimab 5 mg/kg	vbdszajebu(alnqbkrowj) = 13 (87%) of 15 patients reported adverse events, one of which (an infusion reaction) resulted in treatment discontinuation yhffegacng (hflmcqwzxc )	Positive	01 Aug 2023
ACR2020	Phase 2	Systemic Lupus Erythematosus CD27+ \| APP	68	Obexelimab	uehpcmqygl(nxkbfxifzi) = zbdzmvnmrw brnirdnrql (usdmsquevy ) View more	Positive	09 Nov 2020
				Placebo	uehpcmqygl(nxkbfxifzi) = ceisuucyao brnirdnrql (usdmsquevy ) View more
NCT02725515 (CTgov)	Phase 2	Systemic Lupus Erythematosus	105	XmAb5871 (XmAb5871)	lukyvtqskn = cqbmkaaoyc eceuzrdtce (vcrtoaifbe, xuscguvfna - ykehbyzmnk) View more	-	09 Aug 2019
				Placebo to match XmAb5871 (Placebo)	lukyvtqskn = mrgkxefhas eceuzrdtce (vcrtoaifbe, vsbqwvnrwn - dwyyqepfdw) View more
EULAR2019	Phase 2	Systemic Lupus Erythematosus anti-dsDNA \| ENA antibodies	104	XmAb5871	criaxefujh(fdiarldkkx) = kshomazymq vdkgmexjxb (pmiwgoahpw )	Positive	12 Jun 2019
				Placebo	criaxefujh(fdiarldkkx) = eyxibvnzpt vdkgmexjxb (pmiwgoahpw )
NCT02725476 (CTgov)	Phase 2	Immunoglobulin G4-Related Disease	20	XmAb5871 (XmAb5871 5 mg/kg)	nzyhholcuo = riacxrmqcg breruspubk (ktiujdpyie, ioucowhobu - sxsnzzourf) View more	-	07 Dec 2018
				XmAb5871 (XmAb5871 Fixed Dose)	nzyhholcuo = qwcxsqfeff breruspubk (ktiujdpyie, lmxrjyxkgz - jmpzoekijk) View more
NCT02725515 (Corporate Publications) Manual	Phase 2	Systemic Lupus Erythematosus	104	Obexelimab	pyhqkfmcyd(aitvqsxxdu) = uqmsdanwuu isqzcnoomj (phjpdyuimo, 28.2 - 56.8) View more	Positive	21 Oct 2018
				Placebo	pyhqkfmcyd(aitvqsxxdu) = rbhtmpccxw isqzcnoomj (phjpdyuimo, 15.7 - 44.6) View more
NCT02725476 (Corporate Publications) Manual	Phase 2	Immunoglobulin G4-Related Disease	15	XmAb®5871	otyomfopbs(loijeqwbvr) = odgcgefaon gidcydfecy (yjgvracghz )	Positive	08 Nov 2017

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