OncoSec Medical Inc (ONCSQ)

[furbush87]

What new treatment strategies hold most potential?

The future is in combination immunotherapies – I predict they’ll become the backbone in many indications. We just need to figure out how to use current targeted agents and chemotherapies judiciously.

I think the most important question that we need to answer in immuno-oncology now is: how do you make PD-1 non-responders into responders? That’s our current strategy at OncoSec – and our primary candidate is intratumoral delivery of IL-12. As a cytokine, it’s a chief driver of anti-tumoral immunity; it turns on all the mechanisms of antigen presentation and processing that tumors try to suppress, so it’s a good choice for targeting PD-1 non-responders and we’re seeing very good systemic anti-tumor response effects in the clinic so far.

Immunotherapies in general are not innocuous. PD-1’s safety profile is pretty good, but when we combine therapies, we’re going to have to be sensitive to synergistic immunotoxicity. That’s a benefit of moving toward a multimodal therapeutic paradigm, including intratumoral therapy – we can harness the treatment efficacy without the systemic exposure and toxicity. IL-12, for instance, used to be given as a recombinant protein drug; it was efficacious, but quite toxic, which is why it wasn’t pursued further. Giving it intratumorally, we don’t see any IL-12 in circulation, so we aren’t seeing the systemic toxic effects that we know systemic IL-12 administration would produce.

Some of the real luminaries in the literature today are beginning to talk about intratumoral therapy. I think we’ll see these therapies come of age in the next decade; Amgen’s T-VEC, a virus that encodes GM-CSF, has met with some success, but there are a lot of different ways you can approach it and I think others will follow suit.

I also think we’ll come back to DNA damage and repair. Tumors are dependent on their ability to mutate; they have to, because that’s how they defeat the immune system and the chemotherapies we throw at them. But this can be their Achilles heel; they become dependent on DNA checkpoints, unlike normal cells, so we have a therapeutic leverage point. I think we’ll see a resurgence of this as a field to explore.

I think one of the benefits of immunotherapy is that you’re not going directly after the tumor, but instead you’re educating the immune system.