Robert Pierce is presenting today at Fred Hutch, Thomas Building, from 3-4pm.
Should be a good discussion.
In Joe Biden's words, "This is a big f'n deal".
Please see 'I have terminal cancer and I know my friends want to ask, 'Aren’t you dead yet?' published in the LA Times yesterday. I am 99.9999% confident that this op-ed written by Melinda Welsh is ONCS's electroporated IL-12 combination trial for metastatic melanoma. If you haven't read it yet, you should.
This anecdotal efficacy evidence complements 'A Review of Novel Intralesional Therapies for Melanoma, With an Emphasis on a Potential Combination Approach' by Chen and Daud in Oncology Journal, May 15, 2016. In Chen and Daud's piece, the authors describe efficacy in three patients from ONCS's combination Metastatic Melanoma trial.
Looks like some potential problems in IL-12 land. ONCS uses an electorates version of IL-12 DNA.
Also, neoantigen targeting is quickly becoming the new frontier in cancer vaccines. First generation vaccines developed by most companies have failed to elicit significant responses for several reasons.
First, the targeted tumor antigens weren't matching up with vaccine's antigen(s); therefore t-cells weren't attacking the tumor cells.
Second, vaccine antigens weren't being recognized by an individual's immune cells as "foreign"; therefore the body won't create an immune response. Only neoantigens are going to be recognized by the immune system as foreign.
Third, cancer vaccines lacked a mechanism to stimulate expansion of t-cells, memory precursor cells, or mature memory cells; therefore the concentration of tumor infiltrating lymphocytes and memory cells was insufficient to eradicate fast-dividing tumor cells.
Lastly, checkpoint inhibitors weren't being used in combination with vaccines; therefore, even if CD-8 t-cells were activated to attack specific tumor cells, they would be stopped by immune checkpoints.
I think Heat Biologics is ahead of the pack, because they use a heat shock protein platform that is capable of seeking out antigen presenting cells (e.g. dendritic cells), which in turn activates CD-8 t-cells with a multitude of neoantigens (see HTBX's pan antigen strategy). This prevents tumor cells from escaping recognition. Heat's COMPACT vaccine takes this a bit further by including a co-stimulatory molecule, i.e. FC-OX40L, which allows for a much more robust immune response than heat shock protein alone. The co-stimulatory molecule, therefore, theoretically helps to increase the number of tumor infiltrating lymphocytes. The icing on the cake is the immune checkpoint blockers like anti-pd-1 drugs. Usually there are high concentrations of TIL that possess checkpoint pathways, so blocking these checkpoints using anti-pd-1 drugs, like opdivo for example, "takes the brakes off" t-cell attack.
Considering they have reduced a significant portion of their workforce, coupled with trial prioritization, I imagine they have enough runway to get them through the first quarter of 2017. We will have a better sense of where they stand financially in just over a week from now.
I think the key advantage to COMPACT is its ability to stimulate the production of memory precursor and mature memory cells through FC-OX40L. This unique ability provides a durable immune response when compared to the mAbs listed. In other words, it should theoretically prevent cancer recurrence after tumor elimination.
I would like to think the company is heading in the direction of combining their COMPACT-FC-OX40L platform with an anti-pd1 drug for solid tumors. The DURGA results should shed some light on whether or not they take this approach.
It is all about pairing anti pd-1 with a pan antigen vaccine. Cancer vaccines won't be effective unless you have an anti pd-1 component that is used in conjunction with it. Merck is well aware of the synergies between the two.
I wouldn't for a second underestimate HTBX's heat shock protein approach coupled with anti pd-1 therapy. DURGA interim data have been trickling out for NSCLC. Stay tuned because this may become very interesting when they report more interim data.