On May 31, 2017, MabVax Therapeutics (Nasdaq: MBVX) announced it has entered into a sponsored research agreement with Memorial Sloan Kettering Cancer Center (MSK) for the development of novel Chimeric Antigen Receptor (CAR) T-cell therapeutics using antibody targeting sequences derived from MabVax fully-human antibodies. The initial focus of the collaboration will be on CA19-9 expressing tumors, including pancreatic cancer and small cell lung cancer.

MabVax will provide the funding and the antibody targeting sequences. MSK, under the direction of Michael Sadelain, MD, PhD, will conduct the in vitro and animal model work, with a goal of completing investigational new drug (IND) enabling pre-clinical studies. MabVax will have certain rights to the new CAR T-cell candidates developed during the collaboration, including an exclusive time-limited option to license MSK's rights in such inventions.

A Little Background On CAR T

CAR-T is the process of retraining the body's own immune system to find and attack cancerous cells. T-lymphocytes (T cells), which play a central role in the body's adaptive immune system, are genetically engineered (transfected) through the use of a virus to express a receptor (binding domain) for certain antigens. These binding domains are derived from variable fragments of a specific antigen-targeting monoclonal antibody joined by a flexible linker. This gives the modified T Cell the specificity of a monoclonal antibody to target tumor-associated antigens found on cancer cells. Newer generation CAR-T therapies include one or more co-stimulatory domains (CD28, 41BB, OX40) that lead to enhanced cytotoxicity and cytokine secretion with prolonged persistence.

The initial success of CAR T has been in treating B cell malignancies by targeting antigens such as CD19 or CD20, found on both healthy and malignant B cells. Once returned to the patient, these engineered T cells actively find and kill B cells in an effort to eliminate leukemia or lymphoma from the body. Scientists are now starting to have success treating solid tumors by targeting antigens such as EGFR, HER2, and MSLN.

Collaboration Could Develop Superior CAR T Technology 

The goal of the MSK-MabVax collaboration is to develop CAR T-cell therapeutics using antibody targeting sequences derived from MabVax fully-human antibodies. This could provide a meaningful safety and duration advantage over CAR T therapeutics that use the binding domains from mouse antibodies. This is the exact strategy that Novartis (NYSE: NVS) is now deploying with CTL119, a next-generation version of CTL019.

One of the binding domains will be from MabVax clinical-stage candidate, HuMab-5B1. HuMab-5B1 is a fully human monoclonal antibody that targets the tumor-associated antigen CA19-9. CA19-9 is found in 92% of pancreatic cancers and its expression is correlated with more aggressive disease. Other solid tumors that express high levels of CA19-9 include stomach, endometrium, uterus, and colorectal cancers.

Phase 1 clinical studies with HuMab-5B1 show encouraging response in targeting advanced pancreatic cancer. A poster of the Phase 1 data will be presented at ASCO on June 3rd. MabVax is developing a pipeline of products based on the HuMab-5B1, including two radiolabeled constructs, a PET-imaging agent dubbed MVT-2163 and a radioimmunotherapy agent dubbed MVT-1075. MVT-1075 preclinical data shows virtual tumor obliteration for the highest doses tested. I've noted in the past my enthusiasm for MVT-1075, which is ready to enter a Phase 1 study in patients with advanced pancreatic cancer. One of the clinical sites in that program is at MSK.

In this new collaboration, MSK will study the newly created CAR T therapies in both in vitro and animal models of diseases. Initial results with the binding domains from HuMab-5B1 warrant further investigation. Beyond HuMab-5B1, MSK will test a second set of novel antibody targeting sequences provided by MabVax. The goal is to complete IND-enabling work, at which point MabVax has an exclusive option to license certain rights to the candidates for clinical investigation.  

I'm excited to see that this work will be conducted in the laboratory of Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering and Gene Transfer and Gene Expression at MSK. Dr. Sadelain is a pioneer in the field of CAR T and a scientific co-founder of Juno Therapeutics (NASDAQ: JUNO). Beyond Juno, Dr. Sadelain has collaborated with Fate Therapeutics (NASDAQ: FATE) to develop off-the-shelf T-cell immunotherapies.  He has published over 200 papers and sits on the Board of multiple non-profit organizations, including St. Jude Children's Research Hospital and the American Association for Cancer Research. Dr. Sadelain has access to proprietary CAR T technology that might marry well with MabVax fully-human targeting sequences. 

Conclusion

I'm excited to see MabVax enter the CAR T space. Dr. Sadelain is a world-renowned thought leader in CAR T and this collaboration presents interesting potential opportunities for MabVax to benefit from his relationships and access to proprietary and next-generation CAR T technology. He is obviously well connected, but beyond his current work with Juno and Fate, Dr. Sadelain saw something in MabVax' fully-human targeting sequences that piqued his interest.

MabVax will have an opportunity to license and clinical-ready candidates created through this collaboration. I'm hoping that this work acts as a gateway to broader collaborations in both CAR T and in targeting solid tumors with HuMab-5B1 or other unique antibodies in MabVax pipeline.