How and when did your company start, and where are you located?
Punit Dhillon, President and CEO, founded OncoSec in 2011 based on his vision to develop new gene therapy approaches to cancer, which leverage the body's immune system to target solid tumors with precision. OncoSec is publicly traded on The NASDAQ Stock Market and headquartered in San Diego, California, a city that is on the cutting edge of the life science and biotech industries.
How many employees do you have, and how do you find and attract them?
OncoSec has approximately 50 employees led by our Senior Management team. The company's mission to deliver safer and more effective cancer treatments for patients has attracted a diverse and dedicated staff. The company is located in San Diego to take full advantage of the city's dynamic workforce, proximity to healthcare institutions, and research capabilities. As OncoSec continues to grow, we strive to remain adaptable, motivated, and responsive to our new and current employees. To attract top talent, OncoSec offers competitive compensation, health and financial benefits, learning opportunities, and educational resources.
What is the main focus and platform technology of your company?
OncoSec is a biotechnology company pioneering new technologies that harness the body's immune system to fight cancer. OncoSec's core immunotherapy platform, ImmunoPulse™, is designed to deliver DNA-based therapeutics directly into tumors and reverse the immuno-suppressive tumor microenvironment. ImmunoPulse™ can deliver a wide variety of potentially synergistic immune molecules. 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, which drives an effective anti-tumor immune response. To date, data show that ImmunoPulse™ IL-12 can generate an initial local immune response as well as triggering a systemic (abscopal) effect, laying the groundwork for expansion into combination approaches, new tumor indications, and future therapeutic candidates.
Can you provide a short overview of your product pipeline?
ImmunoPulse™ IL-12 is currently in Phase II development for several indications, including metastatic melanoma and triple-negative breast cancer. This includes our Phase II combination trial of ImmunoPulse™ IL-12 and Merck's anti-PD-1 drug KEYTRUDA in patients with metastatic melanoma. On the preclinical side, OncoSec is exploring additional cancer immunotherapy targets and strategies, including co-stimulatory molecules, pro-inflammatory cytokines, and cell trafficking molecules. Preclinical stage molecules target multiple cells and pathways responsible for tumor-induced immunosuppression.
Who is your competition, and what advantage(s) do your products / technology offer?
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 is an approved oncolytic virus therapy delivered via intratumoral injection for the treatment of melanoma lesions in the skin and lymph nodes. However, this therapy uses a virus rather than electroporation as a delivery vehicle. 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 anti-drug immune response, allowing for retreatment. Additionally, there are more options regarding the number of genes delivered. Preclinically, the company has demonstrated the ability to deliver multiple immunomodulatory genes in combination in a single treatment. Moreover, a non-replicating DNA plasmid benefits from simplified safety and regulatory pathways versus viral vectors, which must overcome the potential risks of adverse off-target effects that can be long-lasting. Lastly, there are relatively low manufacturing costs and accelerated time to proof-of-concept with DNA plasmid electroporation compared to viral vector engineering.
What were the “highlights“ in your recent product development?
OncoSec reported positive results from its Phase II Merkel cell carcinoma trial at the 2015 European Cancer Congress. In some patients, ImmunoPulse™ IL-12 led to an increase in tumor-infiltrating lymphocytes (TILs) as well as increased expression of genes associated with inflammation. Importantly, tumor-specific CD8+ “killer” T-cells were found in both treated and untreated lesions following ImmunoPulse™ IL-12 therapy. These key biomarker observations support the hypothesis that ImmunoPulse™ IL-12 promotes both local and systemic anti-tumor inflammation. This study demonstrated that ImmunoPulse™ IL-12 can successfully recruit T-cells to the tumor and promote the pro-inflammatory environment necessary to train T-cells to recognize tumor-specific antigens. This mechanism of action, combined with a favorable safety profile, is what makes ImmunoPulse™ IL-12 a rational choice for combination treatment with anti-PD-1 therapies and other cancer treatments.
What have been the most critical problems in developing products in your field, and how can your company's technology help overcome these problems?
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 that were previously elusive. These therapies function by re-invigorating ‘exhausted’ T cells, allowing them to recognize and attack tumors that have suppressed effective anti-tumor T-cell responses. However, the majority of patients in most tumor types still fail to respond to these agents alone, as they lack sufficient numbers of tumor-infiltrating T cells 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. A conservative estimate places the “non-responder” population at almost 1 million patients with solid tumors every year just in the US. These patients represent a tremendous unmet medical need.
ImmunoPulse™ IL-12 has the potential to convert a significant proportion of the non-responder patients into those who will respond to anti-PD-1 agents. Our clinical data shows that intratumoral IL-12 can promote T-cell recruitment and convert T cell poor into T cell inflamed tumors; we anticipate that this will prime the tumor for synergistic efficacy when co-administered with anti-PD-1.
OncoSec is currently evaluating the combination of ImmunoPulse™ IL-12 with Merck's approved anti-PD-1 agent, KEYTRUDA, in melanoma patients. In this study, patients with tumors that are not considered immunogenic and would not be expected to respond to single-agent anti-PD-1 molecules are selected and treated with the combination. The mechanisms of action of both ImmunoPulse™ IL-12 and PD-1 blockade strongly suggest that combining the 2 treatments may circumvent the limitations of anti-PD-1 associated with a T-cell poor environment and offer increased clinical benefit to a larger percentage of patients.
What is your company's value proposition?
OncoSec is taking the fight directly to the tumor and harnessing the innate power of the body's immune system to recognize and attack cancer. Our technology has the potential to deliver a safe, tumor-localized therapy that drives a systemic anti-tumor immune response. This type of therapy can overcome the limitations of traditional treatments and other immunotherapies that can be toxic when delivered systemically. With local delivery of DNA, our goal is to re-train the immune system to fight cancer and address a great unmet medical need in oncology today: the number of patients who do not respond to anti-PD-1 or other treatments.
What business development strategy do you pursue?
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 or other agents to achieve additive or synergistic anti-cancer efficacy. As we continue to pursue promising combination trials clinically, we are also evaluating beneficial therapeutic combinations preclinically. With these approaches, we are gaining a greater understanding of how our technology can improve upon existing therapies and deliver new and improved ones. As our promising preclinical and clinical database continues to build, OncoSec expects to increasingly attract strategic partners and generate more value for our shareholders.
How does your company attract partners?
OncoSec attracts partners through our innovative technology, expertise in immunology and experienced management team. Since our inception, the Senior Management team has cultivated relationships with some of the most prominent scientists and leaders in cancer immunotherapy from all over the world. We continue to build and strengthen these relationships through our ongoing preclinical and clinical trials and networking opportunities.
Who are your most important collaborators?
OncoSec is privileged to work with several prominent academic medical centers and industry collaborators to conduct preclinical and clinical studies targeting various cancers. This past year, OncoSec has expanded its research capabilities to evaluate additional targets harnessing the ImmunoPulse™ platform. This expansion and growth spawned several new collaborations with industry and academic partners to further advance its research, leverage resources and research from peers, and establish the company as a leader in the immunotherapy landscape. OncoSec's current collaborators include Merck, Plexxikon, Heat Biologics, Stanford University, University of Chicago, University of Pennsylvania, and PerkinElmer.
How do you balance performing work in-house vs out-sourcing?
OncoSec performs most of its activities and functions in-house, including operations, engineering, translational biology, discovery research, and administrative activities. Preclinical and clinical trials are conducted in conjunction with our academic and industry collaborators to test our technology in a variety of tumor indications and combination approaches. OncoSec outsources projects including certain clinical functions when it makes sense from a strategic or financial perspective or when a project can be executed more efficiently by outsourcing vs. in-house.
What are your product development goals for the next 3 years?
OncoSec will continue to advance its innovative technologies for the benefit of patients everywhere and drive shareholder value. The company's clinical development focus in melanoma and breast cancer represents significant opportunities for ImmunoPulse™ in the near term. The company looks forward to announcing data from its clinical trials and continuing to advance its clinical pipeline. By moving novel preclinical combination molecules and the existing ImmunoPulse™ IL-12 program forward, OncoSec aims to establish a partnership, which will allow the company to transition and address commercial market opportunities. For more information, please visit: http://oncosec.com/.