Alloplex Biotherapeutics is a privately held Boston based cellular therapeutics company. Our lead oncology program uses proprietary leukocyte activator cell (LAC) lines which are engineered from a parental tumor cell line, to specifically engage and activate peripheral blood mononuclear cells (PBMC) through their native receptors. The resulting activated PBMC are the therapeutic cells intended for administration back to the patient and are referred to as APEXA® cells for Autologous PBMC EXvivo Activated. APEXA® cells are a broadly activated mixed population as evidenced by proliferation, altered differentiation and enhanced cytokine profile. They are comprised of multiple cell types, with many known to possess anti-tumor activity. The APEXA® cells are comprised of natural killer (NK), natural killer-T cells, TCR-gdpositive T cells, cytotoxic CD8 positive T lymphocytes (CTL), as well as additional minor populations. Remarkably this mixed cell population has the ability to rapidly lyse a variety of tumor lines, at exceedingly low effector to target ratios in anin vitro functional cytolysis assay. Moreover, flow sort data reveal that the cytolytic activity resides in more than one subset of cells; hence this represents a multifaceted tumor killing strategy. The cytolysis activity of the APEXA® cells is dramatically specific as demonstrated by the fact these same cells have absolutely no effect on normal naïve blood cells from either the same or different individual. While the target product profile of our therapy is currently focused on an individualized (autologous) cellular product that can be prepared ex vivofor subsequent multiple IV infusions, the possibility of an allogeneic product is also supported by the data. From the patient perspective, the autologous process requires undergoing a small blood draw of 100 ml and waiting 3-4 weeks until receiving the first dose, whereas the allogeneic experience would be an off-the-shelf product. The first-in-man clinical trial is scheduled for 2Q2020 and will enroll cancer patients with measurable disease, irrespective of tumor type, provided that the patient is not concomitantly receiving an immunosuppressive therapy (e.g. chemotherapy).
Alloplex has developed APEXA® cells through the use of an all human in vitroassay which not only models the intended ex vivoactivation of patient PBMC but is, in fact, the actual procedure to be deployed in the clinic. All the necessary assays required for quality control during manufacturing as well as pharmacodynamic monitoring during patient dosing have already been developed thus de-risking the overall clinical development program. Patient safety risks in our first clinical study will be mitigated by a dose escalation component in every patient. It is anticipated that the APEXA cells, being activated but otherwise normal cells, will retain all the immunologic homeostatic mechanisms and hence improve the safety profile of the product.
Preparing for clinical trials will require upgrading the manufacture of our LAC lines, including sterility testing and master cell bank production followed by multiple GMP production runs to ensure product uniformity. These LAC lines will then be integrated as a key component of the APEXA cell production protocol. Interestingly, since the LAC lines are lysed during the PBMC activation process, the patient will not be exposed to the LACs; only the APEXA® cells. The multidose clinical trial will enroll about 30 patients and require about a year to fully complete but given the rapid lysis of tumor cells exposed to APEXA® cells and the open label nature of the first clinical study, we expect to see a signal of clinical activity within the first quarter of first dosing for each patient. Alloplex has recently launched a $20 M USD Series A process to fund the Phase I study and support the company operations for the next 2-3 years. The program has exceeded all expectations and is on track to support an ambitious target product profile for an anti-tumor cellular therapy. In parallel, Alloplex is also seeking strategic partners and investors; preferably those with a demonstrated commitment to cellular therapies as evidenced by experience with the manufacture and commercialization of cellular therapies.
Alloplex was founded by Dr. Frank Borriello MD, PhD, a Harvard trained immunologist with 20 years in the pharmaceutical industry, serving in diverse roles ranging from clinical development to external innovation assessment and business development. He is joined by Dr. James Lederer, serving as CSO who also holds an Associate Professorship of Surgery at the Brigham and Women’s Hospital. Dr. Lederer is an expert in the injury induced modulation of the immune system. Drs. Borriello and Lederer trained together as immunology post-docs at Harvard in the 1990’s and have remained close collaborators and friends for over 25 years.
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