On September 18, 2023 PharmAbcine Inc. (KOSDAQ: 208340ks), a clinical-stage biotech company focusing on the development of next-generation antibody therapeutics, reported that the Company has received approval from the HREC (Human Research Ethics Committee) in Australia for the Phase 1a/b trial (MarkV-01 Trial) of PMC-309, an anti-VISTA (V-domain Ig Suppressor of T cell Activation) antibody candidate (Press release, PharmAbcine, SEP 18, 2023, View Source;bmode=view&idx=16374112&t=board [SID1234649178]).

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The MarkV-01 trial is a first-in-human, open-label Phase 1a/b study which will proceed in two parts, the first part with PMC-309 monotherapy followed by the second part in combination with KEYTRUDA (pembrolizumab), MSD (Merck & Co., Inc., Rahway, NJ., USA)’s anti-PD-1 therapy. PharmAbcine already announced in December 2022 that the Company signed a clinical collaboration agreement with MSD, under which MSD would supply KEYTRUDA for the combination cohort.

The primary objective of the study is to evaluate the safety, tolerability, and determine the recommended RP2D (Recommended Phase 2 dose) in both parts. The second objective is to evaluate PK profile (pharmacokinetics) and clinical efficacy, including ORR (overall response rate), DCR (disease control rate), and PFS (progression-free survival).

PMC-309 is a novel anti-VISTA antagonizing antibody that can be used for the treatment of various tumor types. It inhibits VISTA, an immune checkpoint receptor mainly expressed on MDSCs (Myeloid-Derived Suppressor Cells) and Tregs (regulatory T cells). By inhibiting the VISTA pathway on immunosuppressive cells, PMC-309 can promote anti-tumor effects by indirectly activating T cells unlike the existing immuno-oncology drugs that directly target and activate T cells. This unique mode of action allows PMC-309 to play a pivotal role in regulating the VISTA-expressing immunosuppressive cells found abundantly in tumor microenvironment.

The antibody already demonstrated in nonclinical studies that it can promote both innate immunity (monocyte activation, M1 macrophage proliferation) and adaptive immunity (T cell activation) unlike the existing drugs, which show notable changes only in adaptive immunity. In addition, the in vivo data showed significantly improved tumor growth inhibition when PMC-309 is used in combination with an anti-PD-1 drug compared to both monotherapies of PMC-309 and an anti-PD-1 drug.

"The approval of our clinical trial for the anti-VISTA antibody marks a significant milestone for PharmAbcine, bringing us one step closer to providing a groundbreaking treatment option for patients with unmet medical needs in the field of immuno-oncology," commented Dr. Jin-San Yoo, CEO of PharmAbcine. "We are very excited to begin this trial and looking forward to evaluating PMC-309’s safety and efficacy across multiple tumor types in both mono and combo therapy."

Dr. Yoo also added, "We are grateful for the collaborative work with MSD and would like to thank everyone, including the regulatory, our colleagues, partners, shareholders, and investors, who has contributed to making this achievement possible."

For more information about the MarkV-01 trial, visit clinicaltrials.gov and search for the reference identifier NCT05957081.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About PMC-309

PMC-309 is a novel IgG1 anti-VISTA antagonizing antibody that can be used for the treatment of various tumor types. By inhibiting VISTA, an immune checkpoint receptor mainly expressed on MDSC and Tregs, it can play a pivotal role in maintaining the immunosuppressive environment around the tumor cells.

In the nonclinical studies, it has been demonstrated that PMC-309 can promote both innate immunity (monocyte activation, M1 macrophage proliferation) and adaptive immunity (T cell activation) unlike the existing drugs which show significant changes only in adaptive immunity. In addition, the in vivo data showed that PMC-309 significantly improved tumor growth inhibition when used in combination with an anti-PD-1 drug compared to both monotherapies of PMC-309 and an anti-PD-1 drug. These findings suggest that PMC-309 can offer a new treatment strategy in immuno-oncology area as it can be used in combination with other drugs to improve their low-response rates.

About MarkV-01 Trial

The MarkV-01 trial is a Phase 1a/b, first-in-human (FIH), open label study to evaluate the safety, tolerability, and PK of PMC-309, a mAb against the human VISTA ligand, in participants with advanced or metastatic solid tumors administered as a monotherapy and in combination with pembrolizumab. The primary objective of the study is to evaluate the safety, tolerability, and determine recommended RP2D in both parts. The second objective is to evaluate PK profile and clinical efficacy, including ORR, DCR, and PFS.

Phase 1a is a 2-part dose escalation; both parts will adopt the modified toxicity probability interval (mTPI) design with a dose limiting toxicity (DLT) rate of 30% for dose finding.

Part A is planned as a PMC-309 dose escalation.
Part B is planned as a PMC-309 dose escalation in combination with pembrolizumab.
Phase 1b is planned as a cohort expansion with PMC-309 administered as a monotherapy (Cohort A) at the preliminary RP2D found at Phase 1a (Part A) and in combination with pembrolizumab (Cohort B) with PMC-309 at the maximum tolerated dose (MTD)/preliminary RP2D found at Phase 1a (Part B).

A minimum of 67 participants are to be enrolled to the study.