RE:RE:ASCO relevanceI am the original Geneman from long ago. My name is Carey Johnson and I don't hide behind a pseudonym. I post on twitter @geneman20042000 but I don't tweet too much about ONCY, for the most part. Medical Degree from Calgary; Pediatrics and Medical Genetics Fellowship UCLA; Howard Hughes Fellowship in Molecular Biology (UCLA). I currently work as a Physician who sees patients with breast, colon, uterine, ovarian cancers for germline, somatic (tumor) DNA testing. Involved in clinical trials but not involved in clinical trials involving ONCY or any other oncolytic virus. I have known about Reovirus since the days of Patrick Lee, Jim Strong, Matt, Peter Forsyth and the damn Science paper that started all of this.
As before, I am interested in exploring the science side but also I like to hear about the various investing theses. Everyone has their own approach, timelines and risk tolerances. As you know, I am not interested in arguing with anyone.
Oncolytic viruses have lost their lustre due to the overwhelming impact of immunotherapies. The IO market will be >US $20B but most patients do not respond to checkpoint inhibitors and other immunotherapies. Viruses have the potential to act as an adjuvant to convert cold cancers to hot and expand the label for existing immunotherapies.
A clinically effective virus has to be cheaply produced and stable. It has to be deliverable - preferably systemically. It has to arrive at the target cancer and not get consumed by a vigilant immune system (or normal tissues). It has to achieve deep penetration into the cancer and undergo efficient replication before alerting host defenses. Ideally, the virus would induce an abscopal effect - either by cascading infection of metastatic disease by progeny virus or (more likely) an immune recognition of distant tumor cells. An ideal virus will have low toxicity to normal tissue and will not set up off-target adverse clinical effects. There are so many hurdles and, so far, there have been limited successes. Companies persist because of the enormity of the market, even with a small extension of the IO labels.
ONCY and Pela have worked their way through many of these things. At least to the point where there are suspicions of actual clinical effect. No regulatory agency will approve Pela without a well designed Ph III trial. If such a trial is designed based on IND213/BRACELET results, the trial will be in first line breast cancer and approval would have to be on surrogate endpoints (response rate, PFS, DFS), Overall survival endpoints on a 100 patient trial (80% reporting) would take many years. Much more difficult to run a registration trial and get approval with surrogate endpoints.
All this to say that the two major issues immediately facing us now are the quality of the updated BRACELET results and the quality of the subsequent partnership. Beyond that is a vast wasteland of FDA meetings, setting up a multinational breast cancer trial, enrollment and data collection.
Let's talk about what is in front of us for the next few months?
Cheers, Geneman