PharmAbcine
Meeting Unmet Medical Needs

The former Prime Minister of Great Britain Benjamin Disraeli once said, “The secret of success is to be ready when your opportunity comes.” – a saying that perfectly surmises the reality of drug discovery and development. All the hard works and preparation done by the scientists and researchers in the processes and clinical research with high costs will meet success when the right opportunity comes.

Take the example of the therapeutic development in oncology, for instance. The therapeutic development in oncology is shifting from the traditional chemical/protein drugs to antibody therapeutics for a better safety profile. When it comes to antibody therapeutics, biotech companies are paying more attention to Bispecific antibodies, Antibody-Drug Conjugates (ADCs), and CAR-T/NK/Macrophage therapies. Moreover, the favorable outcome but low response rates of immuno-oncology (IO) drugs have led to a sharp increase in combination studies and in research efforts to find new IO drugs in recent years. As for combination studies, IO and angiogenesis are the most popular combinations.

This is where companies like PharmAbcine are making a difference. As one of the leading next-generation antibody therapeutics development companies, PharmAbcine specializes in pathological angiogenesis. “Our expertise in the angiogenesis field has helped the company stay ahead of the game given the popularity of angiogenesis drugs in combination studies in recent years, particularly with IO drugs. This as a valuable opportunity for us.”

Olinvacimab, our lead molecule, is undergoing two clinical trials in combination with MSD’s pembrolizumab,” begins Dr. Jin-San Yoo, president and CEO of PharmAbcine. “We recently announced the interim results of the phase I trial of the olinvacimab-pembrolizumab combo study for mTNBC patients. While the patient number is small, the interim results revealed exciting efficacy data – 50 percent ORR and 67 percent DCR in high dose patients.”

Having acquired rich experience in the realm of therapeutic antibody development and antibody engineering, Dr. Yoo founded PharmAbcine—a clinical-stage biotech company developing fully human therapeutic antibodies to treat cancer and neovascular disease—in 2008 with support from the spin-off program of Korea Research Institute of Bioscience and Biotechnology (KRIBB) where he was working as a principal investigator. Despite the global financial meltdown arising from the Lehman crisis, Dr. Yoo secured early funding from Novartis, a multinational pharmaceutical company, and OrbiMed, one of the top venture capital company specialized in healthcare sector investments. Fast forward to today, PharmAbcine has three ongoing global clinical trials. In addition, the company added three first-in-class molecules to its pipeline which will most likely enter a global clinical trial over the next two years.

PMC-403: The Next Generation Therapeutic Drug

At the core of PharmAbcine’s efforts to redefine the future of drug development lies PMC-403 pipeline—the next generation therapeutic antibody candidate to treat neovascular disorders. PMC-403 is a novel agnostic antibody that binds the human Tie2 receptor. PharmAbcine is developing PMC- 403 as a therapeutic drug for both non-ocular and ocular pathological vessel related diseases.

We believe that PMC- 403, with its unique characteristics and wide range of potential indications, will be a game-changer in the bio market

While touching up on the genesis of PMC- 403, Dr. Yoo explains that the interaction between Angiopoietin and Tie2 is involved in the initiation- and late-stage of angiogenesis. Tie2 binding with Angiopoietin 2 (Ang2) destabilizes the blood vessels, while binding with Angiopoietin 1 (Ang1) leads to recruitment of pericytes outside of the endothelial cell, resulting in vessel stabilization. Furthermore, this Ang/Tie2 signaling is tightly linked to vascular endothelial growth factor (VEGF) pathway via a phosphatase called vascular endothelial protein tyrosine phosphatase (VE-PTP). This allows regulating Ang and VEGF pathways if we have Tie2 agonist similar to Ang1. The uniqueness of PMC-403 stems from its ability to bind directly to Tie2 receptors and the only Tie2 activating antibody. Competing molecules indirectly activate Tie2 receptors by either antagonizing VE-PTP or sequestering Ang2. According to Dr. Yoo, these two unique characteristics of PMC-403 will provide a better safety profile in clinical settings.

Considering the leaky and dilated blood vessels in the tumor microenvironment, which inhibit immune cell infiltration into the tumor area, the normalized vessel induced by PMC-403 inhibits dilation of blood vessels, increasing oxygen transfer and allowing immune cell infiltration. PMC-403 inhibits phosphorylation of VEGFR2, a major pro-angiogenic signal and degradation of VE-cadherin, a cell-to-cell junction receptor in the endothelial cells. As a result, pericytes can coordinate well outside of the endothelial cells. This is PMC-403’s mode of action to alleviate hypoxia in the tumor microenvironment. In essence, PharmAbcine has entered into a Materials Cooperative Research and Development Agreement (MCRADA) with the National Institute of Allergy and Infectious Diseases (NIAID) to assess the efficacy of PMC-403 to treat rare vascular disorder Clarkson’s disease or SCLS (Systemic Capillary Leak Syndrome) that have no therapies available currently. PMC-403 intends to change this narrative and has been chosen by Dr. Kirk Druey, Chief of the Lung and Vascular Inflammation Section in NIAID and the foremost expert on SCLS, as a therapy for SCLS over other drug candidates. “There are various diseases caused by abnormal angiogenesis such as wAMD, diabetic retinopathy, acute respiratory distress syndrome, and kidney disease. We believe that PMC-403, with its unique characteristics and wide range of potential indications, will be a game-changer in the bio market,” adds Dr. Yoo.

On a Journey to Help Patients with Unmet Medical Needs

With a strong value proposition in place and a promising future ahead, Dr. Yoo and his team at PharmAbcine strongly believe that they can expand indications for their angiogenesis molecules, especially PMC-403, beyond oncology to non-oncology fields like AMD (age-related macular degeneration), DR (diabetic retinopathy), ARDS (acute respiratory distress syndrome), SCLS, and more. Given the lack of talented research professionals in Korea, PharmAbcine has been operating two 100 percent subsidiaries, one in Brisbane, Australia and the other in South San Francisco, the U.S. to tap into the global human resource pool. Moving ahead, the company is planning to initiate a global phase I clinical trial in an ophthalmology indication like endovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR). PharmAbcine will focus on the clinical trial with intravitreal injection, while the US subsidiary will focus on the development of the eyedrop formulation. As for the development and manufacturing of PMC-403, the company has partnered with Samsung Biologics, a company that will provide the full scope of CDMO services from cell line development, process development, cGMP clinical manufacturing, and to IND filing support.

PharmAbcine will continue to reinforce its R&D platform to effectively and efficiently develop first-in-class drug candidates, thereby licensing out its pipeline assets to global pharmaceutical companies.