Avid Bioservices Inc (CDMO)

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“In Immuno-Oncology, we are not treating the cancer, but treating the immune system. Then the immune system treats the cancer.”

The above statement comes from Dr. Axel Hoos, who is currently vice president, Oncology R&D at GlaxoSmithKline Pharmaceuticals (GSK), and co-director of the Cancer Immunotherapy Consortium (CIC) of the New York City-based Cancer Research Institute (CRI).

Interestingly, Dr. Hoos was also the medical lead in immunology/oncology at Bristol-Myers Squibb (BMS) where he developed the Yervoy (Ipilimumab; anti-CTLA-4) monoclonal antibody in melanoma and other indications.

This post is largely gathered from his 53 minute video, recently shared on this board. In the video he covers the common characteristics of immuno-oncology. The video is well worth a review by immuno-oncology investors. PPHM investors might recognize much of what Dr. Hoos describes, in terms of immuno behaviors and graphic data that we have already seen coming from anti-PS studies and trials.

Much of the following are paraphrased quotes from Dr. Hoos as he describes the newly emerging field of immunotherapy for cancer.

“Combination therapies are the next thing that can really boost the benefit for patients.

Combinations can lift the plateaux of the long term survival tail on a K-M plot curve. For instance, long term patient survival might, through combinations, raise a plateaux from 25% to around 50%, or even higher.

The long term K-M plot survival plateaux in the Yervoy approval trial was around 25%.

Combinations are showing large transformational improvements over Standards of Care.

Dr. Hoos states that for the first time we are starting to talk about cures.

Combinations should:

Balance then intensify the immune system

Increase efficacy: Increase safety.

Early false progression (tumor volume increase) in past trials was not initially recognized as a sign of immune infiltration into the tumors, and some early immunotherapy trials were seen as failures, because of this tumor size increase, and stopped too early.

In immunotherapy trials, tumors initially increase in volume because of immune cell infiltration> inflammation. This initial increase in tumor volume should not be mistaken for tumor progression.

Allow for the time delay as tumors often grow before they start to shrink.

Of importance to PPHM investors with our Bavi + Yervoy melanoma trial, well underway, are some of the characteristics of the K-M plot from the Yervoy phase3 approval trial.

Yervoy melanoma survival curves between the Yervoy arm and the control arm did not separate until after 5 months.

Dr. Hoos explained that this was largely due to the time needed by the immune system, after being treated by the immunotherapy, to build up the necessary adaptive immune response.

http://www.nejm.org/doi/full/10.1056/NEJMoa1003466#t=articleResults

The best ORR for the Yervoy melanoma registration trial was 10.9% for Yervoy alone.

That is not a particularly strong response rate, but it was better than anything previous to Yervoy.

Dr. Rolf Brekken says we should see 200%-300% improvements in response rates when anti-PS is added to immunotherapies like a-CTLA-4 or a-PD-1.

Where might anti-PS Bavi push the Yervoy 10.9% ORR??

Dr. Hoos also talks about redesigning primary and secondary outcome measures for immuno-oncology trials with the FDA to distinguish them from the characteristics of traditional chemo trials. These new measures will fully recognize factors like tumor inflammation when considering PFS, and the exceedingly long overall survivals that are coming from immunotherapies. These long survivals are double edged results. They are wonderful for patients, but can delay initial approvals, and subsequent follow-on standard of care challenges.

As I reviewed the video I was also thinking of the early look-ins for the SUNRISE trial, and what the company and the FDA might be looking for that would signal survival success. Dr. Hoos thinks hazard ratios are particularly useful. He also thinks that a one year survival rate would give a solid picture to company investigators and the FDA of meaningful survival success at a relatively early point in time.

Here’s the video link:

IMO

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