Olinvacimab (anti-VEGFR2 antibody)

Olinvacimab, the lead pipeline, is an anti-VEGFR2 antibody that inhibits tumor growth and metastasis by deterring tumor angiogenesis. It has an ongoing phase II clinical trial in patients with metastatic triple-negative breast cancer (mTNBC).

In the mTNBC study, olinvacimab is being used in combination with Keytruda (pembrolizumab), an anti-PD-1 antibody from Merck Sharp & Dohme Corp. (MSD), for patients in Australia. The phase II study was initiated in December 2021 based on the encouraging result from the phase Ib combo study. The phase Ib study, which began in October 2018, showed 50% Overall Response Rate (ORR), 67% Disease Control Rate (DCR), and no serious adverse events (commonly showed mild reversible capillary hemangioma). This interim result provided strong scientific rationale to proceed to phase II which is currently ongoing and recruiting patients at multiple clinical sites in Australia. The phase II study is expected to be complete by Q4 2024.

PMC-309 (anti-VISTA antibody)

PMC-309 is a monoclonal antibody that targets human VISTA (V-domain Ig suppressor of T cell activation), a novel negative immune checkpoint. It indirectly promotes T cells' immune responses by inhibiting VISTA-expressing immunosuppressive cells, such as MDSCs (Myeloid-Derived Suppressor Cells) and M2 macrophages.

The preclinical data showed that PMC-309, not only activates adaptive immunity (T cells) like the existing anti-PD1/PDL1 and anti-CTLA4 antibodies, but also activate innate immunity by stimulating monocytes. This unique mode of action allows PMC-309 to be used for patients who show low or no response to the existing drugs. In addition, when PMC-309 was used in combination with an anti-PD1 antibody, it showed significantly increased tumor growth inhibition compared to either PMC-309 monotherapy or anti-PD1 monotherapy. The data indicates that PMC-309 can help address the unmet needs in immuno-oncology area in both mono and combo therapies.

PharmAbcine plans to submit a Clinical Trial Application in Q1 2023 for a phase Ia/Ib study in Australia, and the phase Ia study is expected to begin in Q3 2023. Under collaboration with MSD, phase Ib study will include cohort expansion of PMC-309 and Keytruda combination treatment. for a phase I study.

PMC-403, 402 (anti-TIE2 antibody)

PMC-403 is a novel agonistic antibody that binds to human TIE2 receptor. Activation of TIE2 receptors results in a normalization of pathologically leaky blood vessels in vascular-related diseases. It is being developed as a therapeutic drug for vessel-related ocular diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and macular edema.

In the preclinical studies, PMC-403 showed similar retinal leakage reduction to Eylea(aflibercept), the best-selling drug, in ophthalmology market. The significance of this data is that PMC-403’s novel TIE2-activating mechanism can be used in the VEGF-exclusive market to treat patients who show low or no response to the existing therapeutics.

Also, amongst the main pathophysiology factors of vessel-related ocular diseases (angiogenesis, leakage, and inflammation), PMC-403 shows improvement in all three factors, while anti-VEGF drugs show weak effect in controlling inflammation.

In April 2022, the GLP-Tox study revealed that PMC-403 does not show any serious adverse events, meaning it is safe enough to be administered in human trials. On Dec 2022, PharmAbcine submitted an IND for phase I study for patients with wAMD in South Korea. The phase I study is expected to begin in Q2 2023.

The vessel-normalizing mechanism of PMC-403 can also be utilized in many other vascular-related diseases. In August 2020, PharmAbcine signed a Materials Cooperative Research and Development Agreement(MCRADA) with National Institutes of Health (NIH) to conduct collaborative studies in evaluating PMC-403’s therapeutic effect for Systemic Capillary Leak Syndrome(SCLS, Clarkson Disease), a fatal orphan disease with no approved treatments available. From the positive data, PMC-403 was granted Orphan Drug Designation (ODD) from the US FDA on Feb 21st, 2023.

PMC-402 is another TIE2-activating antibody that normalizes pathologically leaky blood vessels. Unlike PMC-403, PMC-402 is being developed to treat diabetic peripheral neuropathy (DPN), one of the common vessel-related complications of diabetes mellitus, that causes paresthesia, loss of sensation, hyperalgesia, and subsequently amputation. Currently, there are only symptomatic treatments available in the market.

PMC-402 is planned to enter a human trial to evaluate its therapeutic effect in stopping the further progression of the disease. The IND package is complete and ready to submit IND for phase I study for DPN patients. for a phase I trial.

Early-stage assets

PMC-005BL is an antibody that specifically targets Epidermal Growth Factor Receptor variant iii (EGFRviii) which is expressed only in cancer cells. It can be incorporated into CAR-T, CAR-NK which are cell therapies that involve altering genes of the extracted T cells and NK cells. Once the engineered cells are infused back into patients, they will target the specific antigens presented on the epitope of certain type of cancers for better anti-tumor effects. PMC-005-CAR-T showed eradication of EGFRviii overexpressing tumors in animal model systems. PMC-005 can also be applied for ADC and RadioImmunoTherapy since it has zero binding to EGFR wild type and only binds to EGFRviii.

PMC-122 is a bispecific immuno-oncology antibody that is being developed to have two versions. One targets PD-L1 and CD47, an inhibitor of cancer-killing immune cells, while the other one targets PD-L1 and SIRPα, a partnering protein for CD47. It can turn off “don’t eat me” signal on cancer cells and result in more favorable environment for phagocytosis.