PharmAbcine Inc. announced that the Company presented an updated preclinical data PMC-309, the Company's anti-VISTA antibody candidate at AACR (American Association for Cancer Research) 2022 Annual Meeting currently taking place both online and offline in New Orleans. PMC-309, one of the company's first immuno-oncology drug candidates, is a monoclonal IgG (Immunoglobulin G) that targets human VISTA (V-domain Ig Suppressor of T cell Activation), an immune checkpoint regulator. VISTA is found overexpressed on MDSC (Myeloid-Derived Suppressor Cells) and M2 macrophages both of which are immunosuppressive cells found abundantly around TME (Tumor Microenvironment).

The new findings from the poster presentation are as follows: 1) PMC-309 indirectly activates T cells by inhibiting VISTA expressions on immunosuppressive cells. 2) It has shown to inhibit MDSCs and M2 macrophages. 3) It activates monocytes, one of key factors in innate immunity, which also led to the proliferation of pro-inflammatory M1 macrophages.

4) The animal model study showed significantly improved tumor growth inhibition when PMC-309 is used in combo with an anti-PD1 drug. The in vitro studies confirmed that PMC-309 inhibits MDSCs and M2 macrophages which created a pro-inflammatory environment. The MDSC inhibition showed dose dependent increase of IFN-y, a pro-inflammatory cytokine, similar to an anti-PD1 drug but higher than an anti-CTLA4 drug.

The M2 macrophage inhibition decreased the proliferation of Tregs (regulatory T cells) while boosted the number of NK (Natural Killer) cells compared to the control group. Both data from Treg and NK cell experiments were superior to that of an anti-PD1 drug. PMC-309 has also shown to activate innate immunity as it increased TNF-alpha, a pro-inflammatory cytokine released by monocytes.

The elevated level of TNF-alpha has also led to polarization of M1 macrophages, which release pro inflammatory cytokines. On the other hand, anti-PD1, anti-PDL1, and anti-CTLA4 drugs showed lower elevation of TNF-alpha and M1 macrophage than PMC-309. Lastly in vivo studies, the experimental mice were administered with PMC-309 to evaluate tumor growth inhibition.

PMC-309 showed notable tumor growth reduction similar to an anti-PD1 drug, but when used in combo with an anti PD1 drug, there was a significantly improved anti-tumor effects than either monotherapies. Likewise, the combo therapy showed better T cell infiltration and MDSC reduction in the tumor microenvironment.