ONCS: OncoSec’s Technology Has the Potential to Transform PD-1/PDL-1 Non-Responder to Responderx
NASDAQ:ONCS Background of Immune Checkpoint Inhibition Immune checkpoint inhibition is the one of the most promising areas for the treatment of cancer. Both CTLA-4 and PD-1/PDL-1 inhibitors have shown impressive results in clinical care and in ongoing clinical studies. Recent approval of Yervoy (CTLA-4 antibody from BMS), Opdivo (PD-1 antibody from BMS), and Keytruda (PD-1 antibody from Merck), demonstrated the importance of immune checkpoint inhibitors in the treatment of cancer. We think the cancer immunotherapy – through immune checkpoint inhibitors – will enter widespread clinical use and command a large market share of the cancer care market within the next decade. Studies have demonstrated that tumors (specifically melanoma) can be divided into a high and low TIL (tumor infiltrating lymphocyte) phenotype. Tumors with high TIL are referred to as immunogenic, while tumors with low TIL are referred to non-immunogenic. Ongoing clinical trials of PD-1/PDL-1 inhibitors suggest that response correlates with high TIL phenotype. Tumors with low TIL have low response rate to PD-1/PDL-1 inhibitors. Anti-PD-1 non-responders constitute the majority of patients even in “immune therapy” tractable tumors like melanoma and RCC. Recent melanoma studies have reported response rates in the range of 20-40% using anti-PD-1 or anti-PDL-1, and the argument is that the majority of the responders are the high-TIL population. If this is the case, then the question becomes how to make those non-immunogenic tumors into immunogenic tumors so that they can respond to PD-1/PDL-1 or similarly effective T cell checkpoint agents. ImmunoPulse™ IL-12: A Potential Paradigm Shift in Cancer Immunotherapy We believe OncoSec’s (ONCS) platform technology and lead candidate ImmunoPulse™ IL-12 has the potential to transform the non-immunogenic tumors (non-responders) into immunogenic tumors (responders) to prime the immune system for PD-1/PDL-1 inhibitors, such as Opdivo and Keytruda. ImmunoPulse™ IL-12 has demonstrated strong efficacy to convert T cell poor tumors to T cell rich tumors in both metastatic melanoma and Merkel cell carcinoma. Since IL- 12 promotes tumor immunogenicity and increases the number of TILs in the tumor, the combination therapeutic concept is that ImmunoPulse™ will convert low TIL tumors into high TIL ones, thus allowing Keytruda/Opdivo to kill tumor in patients, who would otherwise be PD-1 unresponsive. The potential ability of ImmunoPulse™ to convert the non- or weakly immune-responsive cancer into strongly immune-responsive cancer may represent a paradigm shift in cancer therapy. This area is an enormous unmet medical need and represents a huge market opportunity for OncoSec. It is estimated that about 50% to 80% of cancer patients will not have TIL infiltrate at baseline or even after PD-1/PDL-1 treatment. This is where OncoSec’s ImmunoPulse™ can get in and convert those non-immunogenic tumors into immunogenic tumors. In addition to melanoma, ImmunoPulse™ can virtually target any solid tumor, which represents a multi-billion dollar market for OncoSec. There is a huge unmet medical need for OncoSec’s ImmunoPulse™ in combination with checkpoint inhibitors. If we look at the melanoma indication alone, this is a disease that has the highest response rates with PD-1 inhibitor monotherapy. But still there are about 60% to 80% of patients who will not respond to PD-1 checkpoint inhibitors. This powerful combination is expected to treat the larger population of approximately 70% of the patients. In other solid tumors, the percentage of PD-1 non-responders/non-immunogenic tumors is likely to be even greater. Thus, there is a tremendous unmet medical need, across many solid tumors. We estimate the market for the combination therapy will be a multi-billion dollar business. Results from Newly Initiated Phase II Combination Trial Could Lead to a Big License Deal In November 2014, OncoSec initiated a landmark Phase II combination trial in collaboration with the University of California, San Francisco (UCSF) and Merck to evaluate the safety, tolerability and efficacy of Merck’s anti-PD-1 drug, KEYTRUDA® (pembrolizumab) in combination with OncoSec’s ImmunoPulse™ IL-12 therapy for the treatment of metastatic melanoma patients, who are non-responsive to KEYTRUDA®. This Phase II clinical trial is an investigator sponsored trial (IST), with UCSF and Dr. Alain Algazi as the lead investigator. This is a multi-center, open label, single-arm trial, which will enroll approximately 42 patients with unresectable, "low-TIL" metastatic melanoma. The key endpoints of the study include: best Overall Response Rate by RECIST v1.1 and immune related-Response Criteria (irRC); safety and tolerability; duration of response; 24-week landmark progression-free survival; median progression-free survival; and overall survival. The treatment schedule for the trial follows the standard schedule for pembrolizumab. Pembrolizumab will be administered systematically once every three weeks and ImmunoPulse™ IL-12 will be administered on three separate days every six weeks. ImmunoPulse™ IL-12 employs intratumoral delivery of DNA-based IL-12 followed by electroporation. Merck will supply pembrolizumab, and OncoSec will provide ImmunoPulse™ IL-12. This is the first study in the field of immuno-oncology to evaluate the combination of DNA-based interleukin-12 with electroporation and an anti-PD-1/PD-L1 inhibitor. The Phase II combination study will provide the Company with information for a key inflection point in the development of its lead ImmunoPulse™ program. We believe positive data from the Phase II combination study may lead to a major license deal for OncoSec. If the Phase II combination study can confirm safety and efficacy of both agents, a pivotal trial could follow by either OncoSec or Merck in 2016. And we estimate approval of ImmunoPulse™ for the treatment of melanoma may be obtained as early as in 2018 if the pivotal trial data prove to be positive. We believe the combination has the potential to be a powerful approach in the fight against melanoma and other cancers. This Phase II combo study presents a potential to address the unmet medical need of vast majority of the metastatic melanoma patients and has profound implications on many other tumor indications. READ THE FULL RESEARCH REPORT HERE SUBSCRIBE TO ZACKS SMALL CAP RESEARCH to receive our articles and reports emailed directly to you each morning. Please visit our website for additional information on Zacks SCR and to view our disclaimer.
