Special Report

OncoSec Delivers Cancer Therapy Straight to the Tumor

Punit Dhillon Cancer patients often receive multiple rounds of chemotherapy, with new drugs incorporated into treatment programs as tumors develop resistance. OncoSec Medical Incorporated's Punit Dhillon describes how his company is challenging that paradigm with a proprietary platform that delivers therapeutic agents directly to the tumor, while also laying a foundation for expanded use of combination immunotherapies at the forefront of cancer treatment.

Management Q&A: View From the Top

The Life Sciences Report: Can you give us a brief overview of OncoSec Medical Incorporated (ONCS:NASDAQ)?

Punit Dhillon: OncoSec is a biotechnology company focused on developing new technologies that harness the body's immune system to fight cancer. Our core investigational immunotherapy platform, ImmunoPulse™, is designed to deliver DNA-based therapeutics directly into tumors and reverse the immuno-suppressive tumor microenvironment. We have an experienced leadership team, including senior management and scientists who have extensive backgrounds in drug development, cancer immunology and partnering. The company is publicly traded on NASDAQ.

TLSR: Can you outline OncoSec's main focus and current technologies? What does OncoSec's product pipeline look like?

PD: Our mission is to develop safe and effective immunotherapies that can result in clinically meaningful impacts and improve patient outcomes. We believe our core platform, ImmunoPulse™, can deliver a wide variety of potentially synergistic immune molecules.

"OncoSec's pipeline is designed to take the fight to the tumor and reverse tumor-induced immune tolerance on multiple fronts."

OncoSec's lead program, ImmunoPulse™ IL-12, employs this intratumoral technology to enhance the local expression of interleukin-12 (IL-12), which is a critical pro-inflammatory cytokine that drives an effective anti-tumor immune response. To date, our data show that ImmunoPulse™ IL-12 can generate both a local immune response as well as trigger a systemic (abscopal) effect, laying the groundwork for expansion into combination approaches, new tumor indications and future therapeutic candidates.

ImmunoPulse™ IL-12 is currently in clinical development for several indications, including metastatic melanoma and triple-negative breast cancer. This includes our Phase 2 combination trial of ImmunoPulse™ IL-12 and Merck & Co. Inc.'s (MRK:NYSE) approved anti-PD-1 drug, pembrolizumab, in patients with metastatic melanoma. On the preclinical side, OncoSec is exploring additional cancer immunotherapy targets and strategies, including costimulatory molecules, pro-inflammatory cytokines and cell-trafficking molecules. These preclinical-stage molecules can target multiple cells and pathways responsible for tumor-induced immunosuppression.

TLSR: Cancer immunotherapy is a rapidly growing space. What are some key differentiators or advantages of the ImmunoPulse™ technology?

PD: We believe that OncoSec is the only company focusing on intratumoral immunotherapy employing electroporation with DNA-based IL-12. The key advantage—and what has been demonstrated clinically—is the ability of ImmunoPulse™ IL-12 to trigger a coordinated anti-tumor immune response, including a patient-specific neo-antigen "vaccine" response.

There are several advantages to using intratumoral electroporation compared to viral vectors. First, in contrast to viral vectors and many other types of cancer therapies, electroporation of DNA has a low risk of inducing neutralizing antidrug immune response, allowing for retreatment. Additionally, a nonreplicating DNA plasmid is able to benefit from less complex development requirements as compared to viral vectors, which must overcome the potential safety risks of latent off-target effects that may be long-lasting. Lastly, there are comparatively lower manufacturing costs and accelerated time to proof-of-concept with DNA plasmid electroporation compared to viral vector engineering.

"We firmly believe the field of cancer immunotherapy is moving rapidly toward the use of combination therapies, and our intratumoral delivery positions us well to participate in this evolution."

We firmly believe the field of cancer immunotherapy is moving rapidly toward the use of combination therapies, and our intratumoral delivery positions us well to participate in this evolution. With the ImmunoPulse™ platform, there are more options regarding the number of genes delivered. In preclinical studies, we have demonstrated that ImmunoPulse™ has the ability to deliver multiple immuno-modulatory genes in combination in a single treatment. With the next ImmunoPulse™ combination product, our goal will be to deliver multiple DNA-encoded agents directly into tumors that target several facets of tumor immune subversion and, therefore, mount an orchestrated attack to increase tumor immunity. We believe the new product will also leverage our latest advancements in electroporation and further position OncoSec as a leader in utilizing gene electro-transfer technologies in cancer immunotherapy.

TLSR: What are some of the current trends in the immuno-oncology industry, and how are you positioning OncoSec to capitalize on these opportunities?

PD: In oncology, we believe complementary therapies will be crucial to achieving immunotherapy's full potential, and we must continue to test combination therapies that are both safe and effective. Cancer "checkpoint" therapies that block the PD-1 pathway have transformed the oncology landscape in recent years by offering some patients long-term survival benefits. However, the majority of patients in most tumor types still fail to respond to these therapies when given alone. According to recent studies, the reason patients do not respond to these immunotherapeutic agents is likely due to the lack of tumor-infiltrating lymphocytes (TILs)—in particular, T cells that are required for anti-PD-1 therapies to be effective. Consequently, checkpoint inhibitors are only achieving response rates of 20–40%, depending on the specific tumor type. These patients who currently do not respond to anti-PD-1 therapies represent a tremendous unmet medical need.

Immune-stimulating therapies—like ImmunoPulse™ IL-12—have shown an ability to drive TILs into the tumor and stimulate anti-tumor immune activity. The hypothesis is that these priming therapies will increase the response rates for PD-1 checkpoint therapies by driving TILs, which constitute the immunologic prerequisite for effective therapy with anti-PD-1/PD-L1 agents. Our current clinical pipeline is aligned to pursue combination approaches and increase the number of patients who will respond to anti-PD-1/PD-L1 agents.

TLSR: You recently presented combination data at the American Association for Cancer Research's Annual Meeting. What were the main data points and key takeaways from your findings?

PD: New data has emerged from a single-site retrospective analysis of a Phase 2 monotherapy clinical study of ImmunoPulse™ IL-12 in patients with advanced melanoma. After completing treatment with ImmunoPulse™ IL-12, a subset of patients subsequently received an anti-PD-1/PD-L1 therapy either as their next line of treatment or a subsequent line of treatment. Patients with documented follow-up history and evaluable for anti-PD-1/PD-L1 response were included in this analysis.

"Our primary objective is to pursue combination therapies with partners and combine OncoSec's intratumoral DNA-based immunotherapies with checkpoint inhibitors or other immune-oncology products."

In this recently completed Phase 2 clinical study, 34 patients were enrolled and treated with ImmunoPulse™ IL-12. Following their participation on this trial, 14 of these 34 patients went on to receive a systemic anti-PD-1/PD-L1 antibody therapy and were evaluated for their best overall response rate ("BORR") using immune-related response criteria. The PD-1/PD-L1-associated BORR among patients was 64% (9/14). Furthermore, 8 of these 14 evaluable patients received an anti-PD-1/PD-L1 antibody with no intervening therapy after treatment with ImmunoPulse™ IL-12. Of these 8 patients, a BORR of 75% was observed (50% complete response and 25% partial response).

In summary, these data suggest that ImmunoPulse™ IL-12 may prime and enhance response rates to PD-1/PD-L1 blockade, and potentially increase the proportion of patients who will respond to treatment. We expect the results from our ongoing prospective Phase 2 trial combining ImmunoPulse™ IL-12 and pembrolizumab will support and strengthen the findings from the retrospective analysis.

TLSR: What are your product development goals over the next few years?

PD: Our primary objective is to pursue combination therapies with partners and combine OncoSec's intratumoral DNA-based immunotherapies with checkpoint inhibitors or other immune-oncology products. Currently, our clinical programs and research activities are focused on combination approaches that use OncoSec's platform technology with anti-PD-1 antibodies or other agents to achieve additive or synergistic anticancer activity. As we continue to pursue promising combination trials clinically, we are also evaluating other therapeutic combinations preclinically. With these approaches, we are gaining a greater understanding of our technology's ability to enhance the efficacy of existing therapies.

We will continue to execute on our melanoma clinical program as we strive to address a great unmet medical need in oncology. Based on the data presented at AACR and our ongoing combination prospective study, we are focused on the early- and late-stage refractory population to anti-PD-1 as the potential development path for melanoma. With leadership from our clinical and regulatory teams, we intend to use this clinical data to advance our melanoma program to obtain regulatory approval for ImmunoPulse™ IL-12 in combination with anti-PD-1 in advanced melanoma.

We look forward to announcing data from our ongoing clinical trials over the next year. By moving forward our novel preclinical combination molecules and the existing ImmunoPulse™ IL-12 program, we aim to establish a partnership that allows OncoSec to accelerate our current programs and expand our product pipeline in other commercial market opportunities.

TLSR: Would you briefly summarize the major takeaways for investors?

PD: The company has come a long way since it was established five years ago. We've honed a strong path forward for intratumoral immunotherapy, developed a robust portfolio of proprietary gene therapies for cancer, generated positive clinical and preclinical data, and have become a leader in the intratumoral space. OncoSec's pipeline is designed to take the fight to the tumor and reverse tumor-induced immune tolerance on multiple fronts.

Our technology has demonstrated a favorable safety profile and encouraging anti-tumor activity from our clinical trials. We believe our rapid preclinical development platform can validate new targets at a fraction of the cost and time required for other approaches. We have several Phase 2 clinical trials in progress, which are aligned to address a serious unmet need in oncology.

We believe the field of cancer immunotherapy is moving rapidly toward the use of combination therapies, and our intratumoral delivery positions us well to participate in this emerging field of cancer care. For more information, please visit oncosec.com.

TLSR: Thank you for your time.

Punit Dhillon is the cofounder and CEO of OncoSec Medical Incorporated, a biotechnology company developing its advanced-stage immunotherapy to treat solid tumors. He was formerly Vice President of Finance and Operations at Inovio Pharmaceuticals Inc. In his management experience, Mr. Dhillon has raised over $200 million through multiple financings and several licensing deals, including early-stage deals with Merck and Wyeth. His management experience spans corporate finance, M&A, integration, successful in-licensing of key intellectual property, strategy implementation, corporate transactions and collaborations with leading universities, and working with several key opinion leaders worldwide. Mr. Dhillon is also the founder of BeCancerPositive.org, an online community where people can share their experiences with cancer and inspire hope for others. Mr. Dhillon holds a Bachelor of Arts with Honors in Political Science and a minor in Business Administration from Simon Fraser University.

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Disclosure:
1) Tracy Salcedo compiled this interview for Streetwise Reports LLC and provides services to Streetwise Reports as an employee. She owns, or her family owns, shares of the following companies mentioned in this interview: None.
2) OncoSec Medical Incorporated paid Streetwise Reports to produce and distribute this interview. Streetwise Reports does not accept stock in exchange for its services. Click here for important disclaimers. The information provided above is for informational purposes only and is not a recommendation to buy or sell any security.
3) OncoSec Medical Incorporated had final approval of the content and is wholly responsible for the validity of the statements. Opinions expressed are the opinions of Punit Dhillon and not of Streetwise Reports or its officers.
4) Punit Dhillon: I was not paid by Streetwise Reports to participate in this interview. I had the opportunity to review the interview for accuracy as of the date of the interview and am responsible for the content of the interview. I or my family own shares of the following companies mentioned in this interview: OncoSec Medical Incorporated.
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