[Translation] A Phase III, multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of OBEXELIMAB in patients with IgG4-related diseases (INDIGO)

评估活动性IgG4-RD 患者接受GC初始治疗后每周Obexelimab皮下给药对IgG4-RD复发的影响

[Translation]

To evaluate the effect of weekly subcutaneous obexelimab on IgG4-RD recurrence in patients with active IgG4-RD after initial GC treatment

Start Date12 Jan 2024

Sponsor / Collaborator

Shanghai Zenas Biotechnology Co., Ltd.

NCT05786573 / RecruitingPhase 3

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With An Open Label Safety and Dose Confirmation Run-In Period, To Evaluate the Efficacy and Safety of Obexelimab in Patients With Warm Autoimmune Hemolytic Anemia (SApHiAre)

This study aims to examine the efficacy and safety of obexelimab in participants with Warm Autoimmune Hemolytic Anemia (wAIHA).

Start Date25 Sep 2023

Sponsor / Collaborator

Zenas BioPharma LLC.

NCT05662241 / RecruitingPhase 3

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Obexelimab in Patients With IgG4-Related Disease (INDIGO)

This study aims to examine the efficacy and safety of obexelimab for the prevention of flare of IgG4-related disease (IgG4-RD)

Start Date30 Sep 2022

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

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

01 Nov 2023·Revue des maladies respiratoires

Review

Author: Schleinitz, N ; Gaubert, J-Y ; Muller, R ; Habert, P ; Ebbo, M ; Groh, M ; Gaigne, L

INTRODUCTION:

While IgG4-related disease (IgG4-RD) was initially described in the early 2000s, its polymorphic clinical manifestations were previously reported under different names ; they have in common the presence of IgG4+ oligoclonal plasma cells and fibrosis.

STATE OF THE ART:

Ruling out certain differential diagnoses, the diagnosis of IgG4-RD is based on a bundle of clinical, biological and histological features. Chest involvement is variable and can affect the mediastinum, bronchi, parenchyma, pleura and/or, more rarely, bones and (pericardium, aorta, coronary…) vascular structures. The most frequent radiological manifestations are peribronchovascular thickening, mediastinal lymphadenopathy, and nodular or interstitial patterns. Pleural involvement and posterior mediastinal fibrosis are less frequent, while thoracic paravertebral tissue thickening is highly specific. Systemic corticosteroids are the cornerstone of treatment. In case of relapse or as frontline therapy in case of risk factors for relapse and/or poor tolerance of corticosteroids), a steroid-sparing agent (most often rituximab) is added, and biannual maintenance infusions are associated with a lower risk of relapse.

PERSPECTIVES:

An international consensus has recently led to the development of classification criteria that should standardize the diagnostic approach and homogenize the enrolment of patients in epidemiological as well as therapeutic studies. Other treatments are also under evaluation, including biologics targeting T2 inflammation, CD-19 (inebilizumab, obexelimab), SLAMF7 (elotuzumab) surface proteins, Bruton's tyrosine kinase, and the JAK/STAT pathway.

CONCLUSIONS:

Substantial progress has been made over recent years in understanding IgG4-RD pathophysiology, and personalized patient care seems to be an achievable medium-term goal.

News (Medical) associated with Obexelimab

15 May 2024

·www.fiercebiotech.com

Blackstone unearths Uniquity Bio with $300M to explore Merck drug's I&I potential

Uniquity Bio unveiled with full financial backing from Blackstone Life Sciences. What a time to be launching a new biotech focused on inflammation and immunology. Uniquity Bio is the latest such company, unveiled by Blackstone Life Sciences on Wednesday with $300 million and a phase 2-stage lead asset. Solrikitug, an anti-TSLP antibody in-licensed from Merck & Co., was just given the green light by the FDA for two looming studies in chronic obstructive pulmonary disease (COPD) and asthma, respectively. And Blackstone’s head of life science investments suggests the pipeline may soon grow. “We are proud to partner with Uniquity’s team of veteran industry leaders as they advance solrikitug and expand their immunology and inflammation pipeline with additional programs in the near future,” Nicholas Galakatos, Ph.D., said in a release. Consider this announcement a bat signal to the companies that missed out on the Aiolos Bio sweepstakes. That biotech similarly launched with more than $200 million in October 2023 with an anti-TSLP antibody and less than three months later, GSK came calling, buying the company for $1 billion with $400 million in milestone payments up for grabs. Uniquity touts solrikitug as a “highly potent” TSLP receptor binder, with possible application in a wide range of immunology and inflammation conditions. If successful, the company believes it will stand out in an increasingly crowded market. Uniquity expects the space to balloon more than 150% by 2032, with pharmas and new entrants alike seeking an opportunity to challenge AstraZeneca and Amgen’s anti-TSLP asthma med Tezspire. Uniquity is the latest in a series of seismic private financing rounds backing I&I companies. In the past week alone, Attovia Therapeutics launched with $105 million to treat itch conditions and Zenas added $200 million in series C capital for its autoimmune drug, obexelimab. In late March, the former leader of Merck-bought Prometheus launched Mirador Therapeutics with $400 million. Now, Uniquity has entered the fold with the backing of Blackstone’s full purse. “We’re excited about the work that Uniquity has done so far with solrikitug and look forward to providing long-term financial support to the company,” Senior Managing Director Kiran Reddy, M.D., said in this morning's announcement.

AcquisitionIPOImmunotherapyDrug ApprovalADC

08 May 2024

·www.pharmaceutical-technology.com

Zenas raises $200m to advance autoimmune antibody therapy

Zenas, which has recently raised $200m, is evaluating obexelimab in multiple autoimmune disorders, including IgG4-related disease, systemic lupus erythematosus, and more. Credit: Dilok Klaisataporn / Shutterstock. US-based Zenas BioPharma has raised $200m in a Series C round to support the clinical development of its lead candidate, obexelimab. The investors included multiple US-based venture capital companies such as SR One, New Enterprise Associates (NEA), Norwest Venture Partners, Delos Capital, and others. The Series C funds will go towards supporting the “mid to late stage” clinical development programmes of obexelimab, a bispecific antibody that targets CD19 and FcγRIIb. Zenas acquired the rights to the antibody from Xencor in 2021. In September 2023, Bristol Myers Squibb (BMS) acquired the developmental and marketing rights to obexelimab in several Asia Pacific regions, including Australia, Hong Kong, Japan, Singapore, South Korea and Taiwan. BMS made an equity investment in and paid $50m upfront to Zenas, which is also eligible for additional milestone-based payments. Zenas is evaluating obexelimab in a placebo-controlled Phase III INDIGO trial (NCT05662241) as a subcutaneous treatment for IgG4-related disease (IgG4-RD), a chronic fibroinflammatory disease. The study is expected to enrol approximately 200 participants with IgG4-RD. An open-label Phase II/III SApHiAre trial (NCT05786573) is also evaluating obexelimab as a treatment for warm autoimmune haemolytic anaemia (wAIHA). Both the IgG4-RD and wAIHA trials are expected to conclude in late 2025 or early 2026. See Also: China’s NMPA grants breakthrough therapy status for Innovent’s IBI343 FDA grants RMAT designation to Taysha’s Rett syndrome gene therapy Zenas also plans to start Phase II trials investigating the bifunctional antibody as a treatment for multiple sclerosis and systemic lupus erythematosus (SLE), for which obexelimab has previously shown mixed results as a treatment. In 2018, it failed to meet the primary endpoint of maintenance of improvement in SLE in a Phase II trial (NCT02725515). Additionally, the Xencor-sponsored trial did meet the secondary endpoint, with treated patients taking a median of 76% longer to show losses in improvement. The current Series C funds add to the $118m in a Series B round that Zenas raised in 2022. Other autoimmune candidates in the company’s portfolio include ZB002, an anti-TNFα therapy, and ZB004, a cytotoxic T lymphocyte-associated antigen-4 immunoglobulin (CTLA-4-Ig) fusion protein. The two therapies were also acquired from Xencor.

Phase 2Breakthrough TherapyPhase 3Gene TherapyPhase 1

07 May 2024

·www.globenewswire.com

Zenas BioPharma Announces Upsized $200 Million Series C Financing to Advance Mid- and Late-Stage Immunology-Focused Clinical Development Programs

Financing led by SR One, NEA, Norwest Venture Partners, and Delos Capital with significant participation from Enavate Sciences, Longitude Capital, and other new and existing investors Proceeds to support ongoing mid- to late-stage clinical development programs for Company’s lead I&I product candidate, obexelimab WALTHAM, Mass., May 07, 2024 (GLOBE NEWSWIRE) -- Zenas BioPharma, a global biopharmaceutical company committed to becoming a leader in the development and commercialization of inflammation and immunology-directed therapies, today announced the closing of an upsized $200 million Series C preferred stock financing. The financing round was led by SR One along with NEA, Norwest Venture Partners, and Delos Capital with significant participation from Enavate Sciences and Longitude Capital. Additional new investors, the Federated Hermes Kaufmann Funds, and Arrowmark Partners, along with existing investors, Fairmount, Wellington Management, Rock Springs Capital, Pivotal bioVenture Partners, Vivo Capital, Quan Venture Fund, and Superstring Capital participated in the financing. In conjunction with the financing, Jake Nunn, venture partner at SR One, and Tim Xiao, Partner at Delos Capital, joined Zenas’ Board of Directors. Proceeds will support ongoing mid- to late-stage clinical development programs for the Company’s lead product candidate, obexelimab, a bifunctional monoclonal antibody designed to bind both CD19 and FcγRIIb to inhibit the activity of B cells, plasmablasts, and CD19-expressing plasma cells. The obexelimab clinical programs include an ongoing Phase 3 registration-directed trial in IgG4-Related Disease, two planned Phase 2 randomized controlled trials in Multiple Sclerosis and Systemic Lupus Erythematosus, and an ongoing open label Phase 2 trial in Warm Autoimmune Hemolytic Anemia. “We are pleased and appreciative of the support we have received from this group of tremendous life sciences investors as we advance the ongoing obexelimab development program across multiple auto-immune diseases,” said Lonnie Moulder, Founder and Chief Executive Officer of Zenas BioPharma. “Their commitment to Zenas is a testament to our vision to be a global leader in bringing innovative immunology-based therapies to patients around the world. This financing enables us to complete multiple potentially value driving clinical programs.” “We are excited to support Zenas’ continued progress toward its goal of becoming a global leader in innovative immunology-based therapies, and we are confident in the capabilities of this exceptional team to advance the comprehensive development program for obexelimab across multiple potential indications,” said Jake Nunn, venture partner at SR One. “At SR One, we invest in companies like Zenas whose science has the potential to rewrite the medical textbooks and meaningfully transform patient care. We are proud to serve as lead investor alongside an exceptional syndicate and look forward to supporting Zenas in advancing a pipeline of innovative new therapeutic approaches for patients living with inflammatory and immune-mediated diseases.” About Obexelimab Obexelimab is a bifunctional monoclonal antibody designed to bind both CD19 and FcγRIIb to inhibit B-lineage cell activity. Obexelimab has demonstrated clinical activity and was well-tolerated in five clinical trials, including in several autoimmune diseases, in which 198 subjects were dosed. In these clinical studies, obexelimab demonstrated inhibition of B cell function without depleting the cells, resulting in encouraging treatment effect in patients with various autoimmune diseases. Zenas acquired exclusive worldwide rights to obexelimab from Xencor, Inc. Obexelimab is currently being studied in a global Phase 3 clinical study in patients with IgG4-Related Disease and a global Phase 2/3 study in patients with Warm Autoimmune Hemolytic Anemia (wAIHA). Clinical development of obexelimab for Multiple Sclerosis and Systemic Lupus Erythematosus is under way. More information on the Phase 3 (INDIGO) study for the treatment of IgG4-Related Disease is available at clinicaltrials.gov: NCT05662241. More information on the Phase 2/3 (SApHiAre) study for the treatment of wAIHA is available at clinicaltrials.gov: NCT05786573. About Zenas BioPharma Zenas BioPharma is a clinical-stage global biopharmaceutical company committed to becoming a leader in the development and commercialization of inflammation and immunology (I&I) directed therapies for patients in need around the world. With clinical development capabilities and operations globally, Zenas is advancing a portfolio of potentially differentiated autoimmune therapeutics in areas of high unmet medical need. Zenas’ experienced leadership team and network of business partners drive operational excellence to deliver potentially transformative therapies to improve the lives of those facing autoimmune and rare diseases. For more information about Zenas BioPharma, please visit www.zenasbio.com and follow us on X at @ZenasBioPharma and LinkedIn. About SR One SR One is a transatlantic biotechnology venture capital firm that collaborates with entrepreneurs and investment partners in an effort to build elite biotechnology companies. The Company’s mission is to translate innovative technologies and scientific discoveries into next-generation medicines with the potential to benefit patients with significant unmet medical needs. SR One leadership has worked together to build and invest in biotechnology companies for more than a decade. Working alongside the investment team, SR One’s venture partners bring deep operational experience to help company creation initiatives and support portfolio companies with financing and corporate strategies. SR One has offices in Redwood City, CA, and Philadelphia, PA, in the US and London in the UK. For more information, please visit www.srone.com. About NEA New Enterprise Associates, Inc. (NEA) is a global venture capital firm focused on helping entrepreneurs build transformational businesses across multiple stages, sectors and geographies. Founded in 1977, NEA has over $25 billion in assets under management as of December 31, 2023, and invests in technology and healthcare companies at all stages in a company's lifecycle, from seed stage through IPO. The firm's long track record of investing includes more than 270 portfolio company IPOs and more than 450 mergers and acquisitions. For more information, please visit www.nea.com. About Norwest Venture Partners Norwest Venture Partners is a global venture and growth equity investment firm managing more than $15.5 billion in capital. Since its inception, Norwest has invested in more than 700 companies and currently partners with more than 230 companies in its venture and growth equity portfolio. The firm invests in early- to late-stage businesses across key sectors with a focus on enterprise, consumer and healthcare. The Norwest team offers a deep network of connections, extensive operating experience, and a wide range of impactful services to help CEOs and founders scale their businesses. Norwest has offices in Menlo Park and San Francisco, Calif.; Mumbai, India; and Tel Aviv, Israel. For more information, please visit www.nvp.com. About Delos Capital Delos Capital is a life sciences investment firm that partners with extraordinary teams pursuing breakthrough medicines that meaningfully improve the lives of patients. We are a collaborative, global team of seasoned biotech investors, company-builders, operators, and industry analysts, and we aim to serve the companies into which we invest by bringing both capital and substantive biotech expertise. We have designed, built, financed, and supported both novel platforms and approved medicines that strengthen hundreds of millions of lives across the world. Our global team is spread across offices in Cambridge, MA and in East Asia, allowing us to blend deep experiences operating at the epicenter of global biotech venture with proprietary insights into innovations from emerging biotech clusters. Delos Capital currently manages three funds, with ~US$600 million in total capital under management. For more information, please visit www.deloscapital.com. Investor and Media Contact:Argot PartnersZenas@argotpartners.com

Phase 2Phase 3Immunotherapy

100 Deals associated with Obexelimab

External Link

KEGG	Wiki	ATC	Drug Bank
D11496	-	-	DB15032

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Autoimmune Haemolytic Anaemias	Phase 3	US	Zenas BioPharma LLC.	25 Sep 2023
Autoimmune Haemolytic Anaemias	Phase 3	JP	Zenas BioPharma LLC.	25 Sep 2023
Autoimmune Haemolytic Anaemias	Phase 3	IT	Zenas BioPharma LLC.	25 Sep 2023
Autoimmune Haemolytic Anaemias	Phase 3	PL	Zenas BioPharma LLC.	25 Sep 2023
Autoimmune Haemolytic Anaemias	Phase 3	ES	Zenas BioPharma LLC.	25 Sep 2023
Autoimmune Haemolytic Anaemias	Phase 3	TW	Zenas BioPharma LLC.	25 Sep 2023
Autoimmune Haemolytic Anaemias	Phase 3	TR	Zenas BioPharma LLC.	25 Sep 2023
Autoimmune Haemolytic Anaemias	Phase 3	GB	Zenas BioPharma LLC.	25 Sep 2023
Immunoglobulin G4-Related Disease	Phase 3	US	Shanghai Zenas Biotechnology Co., Ltd.	15 Dec 2022
Immunoglobulin G4-Related Disease	Phase 3	JP	Shanghai Zenas Biotechnology Co., Ltd.	15 Dec 2022

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02725476 (Pubmed)	Phase 2	Immunoglobulin G4-Related Disease	15	Obexelimab 5 mg/kg	hsmkgmlvkk(jtpdmsfjzo) = 13 (87%) of 15 patients reported adverse events, one of which (an infusion reaction) resulted in treatment discontinuation qrpfomgyyw (jfwjmpydea )	Positive	01 Aug 2023
NCT02725515 (CTgov)	Phase 2	Systemic Lupus Erythematosus	105	XmAb5871 (XmAb5871)	jujmupkzhh(ijrpfdkosj) = rrbpcdxyhi ovowtmksyz (yvndqbvdes, invfbzksfm - tfqsvdhgkl) View more	-	09 Aug 2019
				Placebo to match XmAb5871 (Placebo)	jujmupkzhh(ijrpfdkosj) = idtmbxumfi ovowtmksyz (yvndqbvdes, lumhavpiof - zrniyzoiul) View more
Phase 2, Double-Blind, Randomized, Placebo-Controlled Study of a Reversible B Cell Inhibitor, XmAb5871, in Systemic Lupus Erythematosus (SLE) (EULAR2019)	Phase 2	Systemic Lupus Erythematosus anti-dsDNA \| ENA antibodies	104	XmAb5871	pjgcdtjesv(qcurhjblhn) = zwkmvrycom frzhedwqfx (wxgumnbocz )	Positive	12 Jun 2019
				Placebo	pjgcdtjesv(qcurhjblhn) = ztwiirufgu frzhedwqfx (wxgumnbocz )
NCT02725476 (CTgov)	Phase 2	Immunoglobulin G4-Related Disease	20	XmAb5871 (XmAb5871 5 mg/kg)	kiyfsyjxru(jqhxbamvmi) = iasmuehcth xjafyinpop (kaznhuonjv, cyxxofzgzu - zsodgqzxjl) View more	-	07 Dec 2018
				XmAb5871 (XmAb5871 Fixed Dose)	kiyfsyjxru(jqhxbamvmi) = akeeycazid xjafyinpop (kaznhuonjv, qjlddptmnk - dzhmbwvkot) View more
NCT02725515 (Corporate Publications) Manual	Phase 2	Systemic Lupus Erythematosus	104	Obexelimab	fyccwordrl(xlxveeoehs) = uqvsafvzym halklfdczh (shnyxzjfkj, 28.2 ~ 56.8) View more	Positive	21 Oct 2018
				Placebo	fyccwordrl(xlxveeoehs) = kwzqzbavfp halklfdczh (shnyxzjfkj, 15.7 ~ 44.6) View more
NCT02725476 (Corporate Publications) Manual	Phase 2	Immunoglobulin G4-Related Disease	15	XmAb®5871	elcracqmpp(fogoifkzos) = mpaakrxavy kiutiusvfa (fclspkgowj )	Positive	08 Nov 2017

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