Sunday, August 31, 2014

Advaxis' Immune Oncology Program Candidate, In New Combo-Studies, With Merck's Pemrolizumab: Prostate Cancers

Yet another class of cancers will now be studied in an immuno-building combination, along with MK-3475 -- Merck's single most promising drug candidate, across the entire company. [And this tidbit comes to us from a kindly anonymous commenter. My regular readers are. . . the best!]

Once again, this bit of news broke while I was traveling, last week. But here it is, from the Advaxis presser -- Advaxis' candidate is called ADXS-PSA:

. . . .Both ADXS-PSA and pembrolizumab are investigational members of a new class of cancer treatments known as immunotherapies that are designed to enhance the body's own defenses in fighting cancer. Preclinical evidence suggests that Advaxis Lm-LLO immunotherapies in combination with a PD-1 inhibitor may lead to an enhanced anti-tumor immune response.

"We are excited to be working with Merck. Equally as exciting is the combination potential of our Lm-LLO immunotherapy with Merck's anti-PD-1 immune checkpoint inhibitor," commented Daniel J. O'Connor, President and Chief Executive Officer of Advaxis. "We believe the combination of Advaxis Lm-LLO cancer immunotherapies and checkpoint inhibitors holds significant promise for the treatment of prostate and other cancers."

Under the terms of the agreement, Advaxis and Merck will collaborate to evaluate the ADXS-PSA/pembrolizumab combination as a treatment for prostate cancer. The Phase 1 part of the trial is designed to establish a recommended dose regimen for ADXS-PSA alone and combined with pembrolizumab, and the Phase 2 portion will assess the safety and efficacy of the combination. Advaxis will sponsor and fund the study and Merck will provide pembrolizumab. The companies will collaboratively oversee the conduct of the study, which is planned to begin in early 2015. Results from the study will be used to determine the path for further clinical development of the combination. . . .

[And just a bit more, from an Onc-Live interview:]

. . .[Advaxis' approach to attacking] immune tolerance involves cells that live inside tumors and send out clouds of biologic chemicals that also can shut down activated T cells in the area. Scientists know these as Tregs and MDSC cells. Even if the T cells get past the PD-1 [which MK-3475 is designed to address] they can still be shut down by Tregs and MDSCs in the tumors. ADXS-PSA has the ability to decrease the number and activity of Tregs and MDSCs inside the tumors in tumor models.

The point behind this combination is that ADXS-PSA stimulates the immune system to generate a new crop of cancer-fighting T-cells that recognize a key target on the tumor cells, PSA. Then the pembrolizumab PD-1 blockade masks PD-1, which the tumor may be hiding behind, and amplifies the number of cancer fighting cells that are produced. Once these cancer-fighting cells get inside the tumor tissue itself, past the PD-1 blockade, they find that the ADXS-PSA had disabled the Tregs and MDSCs inside the tumor, allowing the cancer-fighting cells to do their job and eliminate cancer cells. Therefore, the combination treatment provides a fresh crop of cancer-fighting cells, while at the same time, overcoming two different mechanisms of immune tolerance that could be protecting the prostate cancer inside patients. . . .

Financial terms were not disclosed -- but the Advaxis oncology candidate has a nice pedigree. We will watch it closely. And, interestingly, a good portion of the management team (and board) had deep ties to the former ImClone -- acquired by Lilly some years ago. Now you know. One to watch.

[Just as trivia, as I close out, and head off to bed -- the older Advaxis logo (circa 2011) was unabashedly a Trojan Horse (see small image at lower left, of the main image). That stark (and perhaps provocative) imagery has been softened, muted and stylized -- in the new logo (top left) -- and I can certainly see why. I suppose the company thinks of its cancer killer as using a "Trojan Horse" approach -- to re-ignite the body's own immune system. Still risky imagery (in my view), for a bioscience company. Smile. G'night, one and all of good will.]

No comments: