Hi, I am Dr. Ezra Cohen at University of California, San Diego Moores Cancer Center. I am a professor of medicine and division chief of Hematology-Oncology, as well as the associate director of the Cancer Center for Clinical Research.

Today, I am talking to you about an American Society of Medical Oncology abstract. A Phase 1b personalized neoantigen vaccine that we are presenting at the annual meeting. This was a collaboration with Dr. Stephen Schoenberger from the La Jolla Institute.

The study originated from a number of observations, primarily that every cancer type is truly different when it comes to the genomics. In fact, every individual cancer has different alterations and mutations within it.

Even though we may call them the same histologically, we realize and recognize that there are unique features to every cancer that mandate individualized therapy.

If that is the case, and the understanding, in addition to that, that every immune system responds differently to different stimuli, we began a journey to develop an immunotherapy that is a neoantigen-based vaccine that would truly be individualized. Here are the first data from that clinical trial.

The abstract itself reports on five patients, the first five patients in Cohort A, that received a peptide vaccine. Again, remembering that each vaccine is individualized. I will take you through that process in a moment.

The vaccine was given in conjunction with an adjuvant. Concurrently, with an anti-PD-1 antibod, pembrolizumab, that was supplied by Merck. The generation of the vaccine starts with sequencing the tumor. First, the DNA sequence, and then eventually, the RNA. In the RNA, we begin to understand which alterations are expressed in the cancer.

From there, we take a biochromatic approach that is not based on a prediction model whatsoever, but rather, a hierarchy of the different expressed alterations that we feel are going to be most immunogenic.

That allows us to produce peptides from those, each of those peptides representing the alteration in question. Then, testing those peptides in an ELISpot against autologous T cells that we take from the patient's peripheral blood.

That results in verified and identified neoantigens for each individual patient. We take those peptide sequences and we give them to a manufacturer, who then produces the actual vaccine.

In the first five patients that we report on, what we saw were truly remarkable data. First, and the primary endpoint of the study, consistently, we saw epitope-specific T cells coming up in the post-vaccine blood draw.

That is to say, we looked at the specific T cells that were going to be responsive to the peptides in the vaccine. What we saw in every patient was an increase in those specific T cells and not a broad increase in the entire T cell population, or a broad clonal increase.

We feel like immunologically, at least, from a T cell perspective, we were doing what we meant to do with the vaccine. However, one more step than that, what we saw in the patients where we got sequencing pre and post-vaccine was evidence of immune editing.

That is to say, the alterations that we vaccinated against disappeared in the post-vaccine biopsy, suggesting that not only were we stimulating the appropriate T cells, but those T cells were hitting the target and destroying the clones that expressed those mutations.

Lastly, we did see evidence of clinical benefit in the form of two patients with very prolonged stable disease. In fact, much longer than their prior therapy. Then, one patient, who, in fact, had a response.

All of these data are going to be presented at the American Society of Clinical Oncology Annual Meeting, where we will have an opportunity to answer more of your questions.

This is just the beginning, of course. These are the first five patients. We are currently working on the data for the next 20 patients in Arm C that involved a different adjuvant, a more intensified vaccine dosing, and in Arm D that now enrolls patients with minimal residual or no evidence of disease in an effort to use the vaccine to prevent any disease recurrence.

Those two arms have fully enrolled, and we hope to present data from the next 20 patients in the near future. Moreover, we already have plans for Phase 2 studies in upper GI malignancies and in adenoid cystic carcinoma, two cancers that we feel will lend themselves exceptionally well to this approach.

In general, we feel that this truly is part of the future of oncology treatment. It is immunotherapy that is completely individualized and takes into account not only the genomics of the cancer but the host immune system as well and maximizes those areas of knowledge to yield what we feel will be the best way to stimulate an immune response.

Thank you very much for your attention, and I hope that this was helpful.