These are the final briefings on what I was able to capture what I feel are important developments and/or innovative therapies serving an unmet need that were featured at the 2012 meeting of the American Society of Clinical Oncology (ASCO). ASCO was held from June 1 to June 5 in Chicago IL as the largest meeting of its kind in the world for Pharma and Biotech where cutting edge data is released which can have significant implications for investors.
The two entities I will comment on are Threshold Pharmaceuticals (THLD) and TH-302 which is driving towards an unmet need and Celldex Therapeutics (CLDX) and (CDX-110) with an important development in the cancer vaccine space:
TH-302 by Threshold Pharmaceuticals, Inc.: Threshold Pharmaceuticals specializes in hypoxia activated drugs. I found TH-302 unique in its design/application and I do not see any other approved drugs in this space. A characteristic of cancer is that the center of the tumor tends to have little to no oxygen present because the cancer cells, in dividing, push the blood vessels away. This makes a low oxygen environment (a hypoxic microenvironment) in which the cancer cells don't need the oxygen to live and it is incredibly difficult to get lifesaving chemotherapeutic drugs in there. Threshold Pharmaceuticals apparently specializes in this space and TH-302 is their flagship product. The importance of this area is that for the majority of tumors, the invasiveness and aggressiveness of the tumor is directly correlated to its lack of need for oxygen. The issues with other drugs that have attempted to do what Threshold Pharmaceuticals is doing is that they ultimately did not penetrate well or have suffered a loss of specificity when modified to help them traverse to the hypoxic regions of the tumors. Threshold feels they have overcome this. They presented data from an ongoing phase II study which is encouraging: a randomized phase III, multi center, open-label study which was initiated September 2011 with a Target goal of 450 patients. The latter comparing TH-302 in combination with doxorubicin versus doxorubicin alone in subjects with locally advanced unresectable or metastatic soft tissue sarcoma. If they succeed, this may have significant potential with such an unmet need. Keep an eye on Threshold.
Rindopepimut® (CDX-110) by Celldex Therapeutics, Inc.: Celldex Therapeutics had one presentation on a phase II study of rindopepimut (CDX-110) plus bevacizumab (BV) in relapsed glioblastoma multiforme (GBM). Rindopepimut® (CDX-110) is an immunotherapy that designed to activate the patient's own immune system against tumor cells expressing EGFRvIII, an activated mutation of the epidermal growth factor receptor (EGFR) which is a protein that has been well validated as a target for cancer therapy. While many different tumors express this antigen, Glioblastoma multiforme, the most common and most aggressive malignant primary brain tumor in humans, has been the first indication sought for approval for the drug. Approximately 30% of newly diagnosed GBM cases overexpress EGFR where it is linked to poor long-term survival.
Bevacizumab (Avastin™), Roche-Genentech (OTC:RHHBY) is a drug that slows angiogenesis, the growth of new blood vessels. Combining Rindopepimut with BV, which inhibits VEGF and its immunosuppressive properties, was investigated to further optimize this EGFRvIII-specific immune response and antitumor activity of the CDX-110 drug. In this study combining CDX-110 plus BV, they showed consistent and encouraging results across 3 phase II studies in newly diagnosed, resected EGFRvIII+ GBM representing a statistically significant improvement over a historical control (median overall survival [OS] = 24.4 - 24.6 vs. control 15.2 months from diagnosis and median progression (disease)-free survival [PFS] = 12.3 - 15.3 vs. 6.4 m) with the study still maturing. They noted that the immunosuppressive influence of residual/advanced GBM presents a challenge to drug activation of the immune system against the tumor but this is not surprising in highly advanced cases because the immune system is suppressed. They also noted anecdotal evidence looking at compassionate use cases (when the patient is highly advanced) suggesting that CDX-110 may induce specific immune responses and regression in multifocal and bulky residual tumors (tumors that are not able to be removed via surgery anymore). These are positive developments in the progress of the drug and for the cancer vaccine space in general.