|Dr. Yoo’s interview with Chosun-ilbo (Chosun Daily) in May 2021
In May 2021, Dr. Jin-San Yoo, Chairman and Chief Executive Officer of PharmAbcine, had a press interview with Chosun Daily to highlight the company’s recent R&D activities and future plans.
Q1. What is the rationale behind the phase II olinvacimab and pembrolizumab combo trial in metastatic Triple-Negative Breast Cancer (mTNBC) in collaboration with MSD?
PharmAbcine and MSD agreed to plan for the phase II trial because both parties believe that the olinvacimab-pembrolizumab combo therapy can provide a great therapeutic option for mTNBC patients who do not respond to the existing drugs.
Although the existing drugs have a high response rate of 50+%, they only offer efficacy to those patients with high PD-L1 expression levels. In contrast, the olinvacimab-pembrolizumab combo showed similar efficacy data regardless of PD-L1 expression level.
The interim result from the phase Ib study showed no serious safety issue with 50% Overall Response Rate (ORR) and 67% Disease Control Rate (DCR) in the high olinvacimab dose cohort. This is a significant finding because the pembrolizumab mono study only showed 9% ORR in mTNBC.
The data from the phase Ib trial gave us an added confidence for taking the combo therapy to phase II. The company has already signed a clinical collaboration for the phase II with MSD and will submit an IND filing soon.
Q2. PMC-403, one of the company’s preclinical assets, is targeting age-related macular degeneration as one of many possible indications. What is this disease and the trend in the market?
Age-related macular degeneration (AMD) is an eye disease caused by macula, a part of the retina, being damaged due to age progression. It can lead to blurred central vision and even blindness.
There are two types of AMD, dry and wet. Unlike dry AMD that progresses slowly over several years, wet AMD causes faster vision loss resulted from growth of abnormal blood vessels in the back of the eye. Among these two types, wet AMD will be the main indication of PMC-403 because PMC-403 can repair damaged blood vessels in the back of the eye.
The global AMD market was approximately USD 1.5 billion in 2020 and is projected to reach USD 2.64 billion by 2026. This growing market is currently dominated by VEGF-A targeting drugs such as aflibercept (Eylea®), ranibizumab (Lucentis®), bevacizumab (Avastin®), etc. Lack of drugs that bind to other targets create unmet medical needs for patients who show low or no responses to the existing drugs.
Q3. What were you able to discover from the nonclinical data of PMC-403 presented at ARVO 2021?
We discovered the following three key findings from the nonclinical data of PMC-403.
First, not only PMC-403 showed vessel normalization, but also decreased the level of angiogenesis regulators. Angiogenesis regulators such as VEGF-A and Ang2 are known to be released excessively in neovascular eye diseases and help worsen the disease. This data indicates that PMC-403 can be a radical treatment drug, instead of the existing drugs that temporarily mitigate the symptoms.
Second, it reduced the size of retinal leakage comparable to aflibercept-controlled group. Despite having a different mode of action, PMC-403, a TIE2-activator, demonstrated its own competitiveness with similar therapeutic effects to the leading VEGF-A- targeting eye drug in the market.
Third, it improved optic nerve responses by nearly 200% compared to the control group which is significantly higher than the aflibercept group. The rise of intraocular pressure from retinal leakages damages optic nerve in the eye and leads to blurred view and blindness. The existing drugs have shown very little vision improvement effects, and this data suggest that PMC-403 can be a solution to help restore impaired vision.
Q4. What is the collaboration agreement with U.S NIH about?
In August 2020, we signed a Material Cooperative Research and Development Agreement (MCRADA) with U.S National Institutes of Health (NIH). This is to evaluate potential therapeutic effects of PMC-403 in Systemic Capillary Leak Syndrome (SCLS, Clarkson Disease) through preclinical models.
Clackson Disease is a fatal orphan vascular disease in which blood vessels leak fluids from the bloodstream into surrounding tissues. This leads to life-threatening conditions such as severe hypotension, hypoalbuminemia, and a decrease in plasma volume. There are currently no therapies available for this disease.
The significance of the collaboration studies is that Dr. Kirk Druey, the chief of the Lung and Vascular Inflammation Section in National Institute of Allergy and Infectious Diseases (NIAID), chose PMC-403, the world’s first vessel normalizing antibody, for the study. This shows the level of interest in PMC-403 among the leading scientists.
Q5. What were you able to discover from the nonclinical data of PMC-309 presented at AACR 2021?
We presented three key findings from the nonclinical data of PMC-309 at this event.
First, we identified that PMC-309 indirectly activates T cells by binding to VISTA, an immune checkpoint regulator expressed on immunosuppressive cells, most notably, Myeloid-derived suppressor cells (MDSCs). This distinct mechanism makes PMC-309 a potential drug for patients who show low response or developed resistance to the direct T cell activating PD-1/L1 drugs.
Second, not only PMC-309 inhibits MDSCs but also lowers the number of MDSCs by inducing phagocytosis. The in vitro study showed that once PMC-309 binds to MDSCs, it induces macrophages to engulf and dissolve the immunosuppressive cells. This finding demonstrates that PMC-309 can have a significant immune-boosting effects.
Lastly, PMC-309 has shown a better anti-tumor effect when used in combo with a PD-1 drug. Although PMC-309 itself showed comparable tumor growth inhibition to a PD-1 drug, the combination of these two drugs showed bigger reduction in tumor growth than their respective mono therapies.
Q6. What are the upcoming events?
We expect to get an approval from Human Research Ethics Committees (HREC) for the phase II olinvacimab-pembrolizumab combo trial in mTNBC in 3Q2021. We are working on an IND filing with Korea Ministry of Food and Drug Safety (MFDS).
We have already initiated GLP-Tox studies for our preclinical assets such as PMC-403, PMC-309, and PMC-402 to establish their safety profile before entering clinics. The finalized data will be available next year, and we expect the clinical trials to start later in the year.