Innovent Biologics, Inc., a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, announces that the results of the Phase 1a study (NCT03763149) of CD47 monoclonal antibody (IBI188, letaplimab) in monotherapy for advanced malignancies, were presented in the form of ePOSTER at the 35th annual meeting of Society for Immunotherapy of Cancer (SITC 2020).

The NCT03763149 study is a phase 1a clinical study evaluating the tolerability, safety, and PK/PD properties of IBI188 (letaplimab) as monotherapy for advanced malignancies that failed in standard treatments. The study preset 7 dose groups ranging from 0.1mg/kg to 30mg/kg. Letaplimab was given once a week until disease progression, toxicity intolerance, or other conditions requiring treatment termination.

A total of 20 subjects were enrolled in this study. As of June 18, 2020, letaplimab completed all the preset doses (maximum dose was 30mg/kg QW) without dose-limiting toxicity and was well tolerated in general. Most of the treatment-related adverse events were grade 1-2, with no drug-related adverse reactions leading to permanent discontinuation and treatment-related deaths. In addition, the overall incidence of anemia was 15% (3/20), with only one subject (5%) had experienced grade 3 transient anemia on the first day of the study drug administration but recovered on the next day. Meanwhile, anti-tumor activity was observed in the monotherapy of letaplimab in this study, with multiple patients obtained stable disease for long period.

At present, Innovent successively completed the phase 1a studies in both United States and China to explore the safety of letaplimab with dose expansion up to 30mg/kg. With a total of over 60 subjects enrolled, letaplimab was well tolerated generally. Innovent is conducting a Phase 1b/3 study in China 'Evaluating the Safety and Efficacy of IBI188 in Combination With Azacitidine in Subjects With Newly Diagnosed Higher Risk Myelodysplastic Syndrome (MDS)' , and a Phase 1b/2 study in China 'Efficacy and Safety Evaluation of IBI188 in Combination With Azacitidine in Treatment of Patients With Acute Myeloid Leukemia (AML)' . In United States, Innovent is conducting a Phase 1b study 'Evaluating the Safety and Efficacy of IBI188 in Combination With Azacitidine in Subjects With Newly Diagnosed Higher Risk Myelodysplastic Syndrome (MDS)'.

The principal investigator Amita Patnaik from South Texas Accelerated Research Therapeutics (START), stated: " In recent years, immune checkpoint inhibitors have become the focus of intensive research. Letaplimab developed by Innovent  Biologics, is a recombinant fully humanized IgG4 monoclonal antibody targeting CD47. The present clinical study demonstrates that letaplimab is well tolerated, with a similar safety profile compared to other anti-CD47 antibodies. Evidence of durable stable disease was observed for letaplimab when administered as monotherapy during the study, which may serve as the rationale for investigating its role in future combinatorial strategies."

" Letaplimab is a global leading anti-CD47 antibody," said Dr. Hui Zhou, Vice President and Head of Medical Science and Strategy Oncology of Innovent. "CD47 is another well-known target after PD-1/PD-L1. Anti-CD47 molecules are under investigation by more than a dozen of companies worldwide, while most are still in phase 1a dose escalation stage. Innovent has successively completed the phase 1a studies in both United States and China, which explored the safety of letaplimab with dose expansion up to 30mg/kg in a total of over 60 subjects. Meanwhile, anemia during CD47 treatment has been one focus area of CD47 drugs, while the safety data in our phase 1a study showed that letaplimab was safe and generally well tolerated, which provides powerful support for the further investigation of letaplimab. Therefore subsequent clinical studies of letaplimab in combination with other agents in a variety of tumor types have already been planned."

"We are now conducting multiple clinical studies in China and United States, further exploring the efficacy and safety of letaplimab in MDS and AML indications. In addition, as an innate immune checkpoint inhibitor, letaplimab has a synergistic anti-tumor effect with T-cell immune checkpoint inhibitor. Innovent will conduct clinical studies of letaplimab combined with TYVYT?(Sintilimab injection) in the treatment of multiple solid tumors."

About Letaplimab

Letaplimab, or IBI188, is a recombinant fully humanized IgG4 monoclonal antibody targeting CD47. CD47 is a transmembrane protein that blocks phagocytosis of macrophage by binding to the signaling regulatory protein (SIRP) on the surface of macrophage, to send a "don't eat me" signal. After blocking this myeloid checkpoint, letaplimab enhanced phagocytosis of tumor cells and cross-activated T cells.

Preclinical data showed that letaplimab had clear target, clear mechanism of action and significant efficacy. The drug was administered continuously for 4 weeks, and the maximum dose without serious toxicity was 100 mg/kg QW. Phase 1a clinical data showed that the escalation of all the preset doses has completed, with the highest exploratory dose of 30mg/kg QW. No dose-limiting toxicity occurred in each dose group, and letaplimab was well tolerated generally.

About NCT03763149 Trial

NCT03763149 is a phase 1a clinical trial conducted in the United States to evaluate the tolerance, safety, and PK/PD properties of Letaplimab monotherapy for advanced malignancies.

In this study, 7 dose groups ranging from 0.1mg/kg to 30mg/kg were preset. Letaplimab was administered once a week until disease progression, toxicity intolerance, or other conditions requiring treatment termination.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop and commercialize high quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, metabolic, autoimmune and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong, S.A.R., China Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 23 valuable assets in the fields of cancer, metabolic, autoimmune diseases and other major therapeutic areas, with three products, TYVYT? (sintilimab injection), BYVASDA? (bevacizumab injection) and SULINNO? (adalimumab injection), on market, one asset under NDA review with priority review status, four assets in Phase 3 or pivotal clinical trials, and additional 15 molecules in or close to clinical trials. TYVYT? (sintilimab injection) has been the only PD-1 inhibitor included in the NRDL since 2019.

Innovent has built an international team with expertise in cutting-edge biological drug development and commercialization. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, Alector, MD Anderson Cancer Center, Hanmi and other international partners.