Allogene is developing allogeneic chimeric antigen receptor T cell (AlloCAR T™) therapy to find the next immunologic breakthrough in cancer.
Autologous CAR T has produced remarkable responses in some cancer patients for whom all other treatments had stopped working. Despite successful patient outcomes for many, these autologous CAR T therapies have certain limitations, including: • Lengthy wait time in patients with very poor prognosis • Not all eligible patients may receive therapy • Compromised T cells in patients may affect product potency • T cell variability may result in unpredictable treatment outcome • Complicated logistics and inefficiency of scale • Limited availability • Creating an inventory of individualized therapy is not an option • The potential for retreatment is limited by available patient starting material Allogene is working to overcome the limitations of autologous CAR T therapies by creating AlloCAR T therapies. Unlike autologous cell therapy, AlloCAR T therapy uses T cells from healthy donors. These cells are isolated in a manufacturing facility, engineered to express CARs to recognize and destroy cancer cells, and modified via gene editing to limit autoimmune response when given to a patient. These therapies are then stored for off-the-shelf use on demand. We believe allogeneic CAR T therapy, which has demonstrated efficacy on par to that of autologous therapies in our Phase 1 trials, can address the key challenges of autologous treatment by: • Treat all eligible patients • Repeat dosing, if needed • No need for complex logistics • Scalable and efficient manufacturing • Potential to treat 100+ patients from a single manufacturing run • Lower ancillary costs • Off-the-shelf for on-demand treatment • Less product variability • Multiplex gene-engineering and gene-editing capabilities • Opportunity for product optimization
If approved, Allogene’s ALLO-501A, followed by other AlloCAR T products, would be the first allogeneic CAR T therapies available for patients. In Phase 1 trials, Allogene has demonstrated efficacy and safety results on par with autologous therapies. Allogeneic therapies have several key advantages that we believe will differentiate them in the clinic. First, AlloCAR T therapies will be available for nearly every patient, even those with the most advanced cancers. In the ALPHA trial of ALLO-501, 98% of enrolled patients received ALLO-501 within a median time of five days from enrollment to start of therapy. That includes those with advanced tumor burden who may have weakened T cells to donate or who don’t have weeks to wait for therapy. In comparison, with autologous therapy, 10 to 30% of patients are unable to receive treatment due to progression or manufacturing issues. AlloCAR T’s will be available off-the-shelf, ready for a patient within days of request. Second, AlloCAR T therapies allow for consolidated, or redosing. This critical differentiator not available for autologous therapies will allow us to push response rates well above those achieved using autologous CAR T therapies. The key to this is ALLO-647, our proprietary anti-CD52 lymphodepletion agent. Because AlloCAR T cells are CD52-free, they will not be harmed by the regimen and can be supplemented with a second dose of AlloCAR T cells Finally, we plan to also pursue AlloCAR T therapies for use in solid tumors where autologous therapies have yet to demonstrate therapeutic benefit.
We have assumed Pfizer’s strategic collaboration and licensing agreement with Cellectis to utilize its TALEN® gene-editing technology with exclusive rights to develop and commercialize previously defined allogeneic CAR T therapy programs directed at select targets. We also have an exclusive worldwide collaboration and license agreement with Notch Therapeutics, an immune cell therapy company creating universally compatible, allogeneic T cell therapies for the treatment of diseases of high unmet need, to research and develop induced pluripotent stem cell (iPSC) AlloCAR™ therapy products for initial application in non-Hodgkin lymphoma, leukemia and multiple myeloma. Under the partnership, we plan to create allogeneic cell therapy candidates from T cells or natural killer (NK) cells using Notch’s Engineered Thymic Niche (ETN) platform. We have a clinical trial collaboration agreement with SpringWorks Therapeutics, a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer. This agreement will evaluate ALLO-715, our investigational anti-B-cell maturation antigen (BCMA) AlloCAR T™ therapy in combination with SpringWorks’ investigational gamma secretase inhibitor (GSI), nirogacestat, in patients with relapsed or refractory multiple myeloma. We have a research collaboration agreement with Stanford University to investigate a novel nucleic acid delivery system to more effectively, safely and flexibly deliver intracellular RNA or DNA into lymphocytes. Working with Baylor College of Medicine, we are exploring the use of alloimmune defense receptors (ADRs), which recognize and destroy immune cells, to allow for greater persistence of AlloCAR T therapies.