On May 23, 2024 I-Mab (the "Company") (NASDAQ: IMAB) a U.S.-based, global biotech company, exclusively focused on the development and potential commercialization of highly differentiated immunotherapies for the treatment of cancer, reported that Gerald Falchook, MD, and the team at I-Mab’s partner for ragistomig (or "ABL503"), ABL Bio (KOSDAQ: 298380), will present a poster related to Phase 1 data for ragistomig at the 2024 American Society for Clinical Oncology Annual Meeting ("ASCO 2024"), taking place from May 31st to June 4th at the McCormick Place Convention Center in Chicago, IL (Press release, I-Mab Biopharma, MAY 23, 2024, View Source [SID1234643603]).

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Ragistomig was designed as a bispecific antibody to provide anti-PD-L1 activity and 4-1BB-driven T-cell activation in one molecule. The combination of an Fc-silent and conditional 4-1BB engagement was intended to optimize the compound for safety, including the potential for lower hepatotoxicity compared to traditional 4-1BB agonists.

The first-in-human Phase 1 study was designed to define the dose-limiting toxicity and safety profile of ragistomig monotherapy (primary endpoints) as well as to observe the objective response rate (ORR), pharmacokinetic (PK) and immunogenicity profiles (secondary endpoints). The study is being conducted in patients with advanced or relapsed/refractory solid tumors and the majority of patients (56.6%) received prior anti-PD(L)-1 immunotherapy. The main observations from the study include:

· A manageable safety profile;

· Definition of an optimal dose of 5 mg/kg, with dose proportional pharmacokinetics (PK);

· Overall response rate of 25% at 5 mg/kg, based on 3 partial responses (PR) out of 12 patients with median progression free survival (PFS) of 15.6 weeks;

· Clinical benefit rate of 75% at 5 mg/kg, based on 3 PRs and 6 stable disease (SD);

· 71.4% of responders had received prior anti-PD-(L1) inhibitors and were all relapsed or refractory to anti-PD-(L1) inhibitors; and

· A complete response (CR) was seen in one heavily pretreated patient (7 prior lines of therapy, ovarian cancer) at 3 mg/kg.

"We are pleased to present the Phase 1 data to date for ragistomig at ASCO (Free ASCO Whitepaper) 2024. While immune checkpoint inhibitors have made a significant contribution to the treatment of solid tumor cancers, many tumors do not respond or become refractory to these agents. Ragistomig was designed to provide a new treatment option for patients who are resistant to immune checkpoint inhibitors," said Raj Kannan, Chief Executive Officer at I-Mab. "Topline data indicate that the study met its objectives, enabling the definition of an optimal dose, and provided several early efficacy observations in patients relapsed or refractory to prior checkpoint inhibitor treatment. These data support further development of ragistomig as both a monotherapy and in combination with other compounds. We look forward to advancing the clinical program in collaboration with our partner, ABL Bio."

Louie Naumovski, MD, PhD, Interim Chief Medical Officer for I-Mab commented, "We are pleased by ragistomig’s manageable safety, T-cell activation profile and dose proportional pharmacokinetics. Observation of responses is also encouraging, including a 25% ORR and a 75% clinical benefit rate (CBR), at the optimal dose of 5 mg/kg. Notably, the majority of patients were heavily pretreated, with three or more lines of therapy, including a prior PD-(L)1 inhibitor, and the majority of responders (71.4%) had received prior anti-PD-(L)1 therapy. Together, these data provide sound support to continue the development of ragistomig, with ongoing follow-up of this initial Phase 1 study."

The data will be reported in a poster entitled "Phase 1 trial Safety and Efficacy of Ragistomig, a Bispecific Antibody Targeting PD-L1 and 4-1BB in Advanced Solid Tumors" (Abstract #2529, Poster Board 8), at ASCO (Free ASCO Whitepaper) 2024 on June 1, 2024 from 9:00 a.m. – 12:00 p.m. C.D.T. in the Developmental Therapeutics – Immunotherapy session by Dr. Gerald Falchook, MD, Director of the Sarah Cannon Research Institute at HealthONE, a clinical trials program in Denver, Colorado, for patients with advanced cancer.

About Ragistomig

Being developed jointly with ABL Bio, ragistomig (also known as ABL503) is a differentiated PD-L1-based bispecific antibody that fuses an Fc-silent anti-PD-L1 arm, as the tumor-dependent T-cell activator, with a single chain variable fragment of an anti-4-1BB engaging antibody, as the conditional T-cell activator, upon tumor engagement. Using ABL Bio’s "Grabody-T" bispecific antibody platform technology, ragistomig/ABL503 stimulates 4-1BB activation only in the presence of PD-L1 expressing tumor cells to minimize the risk of off-tumor toxicity and overcome resistance to PD-(L)1 inhibition. Preclinical studies have demonstrated that the bispecific antibody shows better anti-tumor activity than equimolar doses of single agents alone or in combination. A Phase 1 dose escalation and dose expansion study (NCT04762641) is currently being conducted in the U.S. and South Korea. The study was designed to define the dose-limiting toxicity and adverse event profile of ragistomig (primary endpoints) as well as to observe the objective response rate, pharmacokinetic and immunogenicity profiles (secondary endpoints).