About OncoSec Medical
OncoSec Medical Incorporated, a late-stage immuno-oncology company, focuses on designing, developing, and commercializing proprietary, intra-tumoral DNA-based therapeutics to stimulate and to augment anti-tumor immune responses for the treatment of cancers. The company’s core technology platform ImmunoPulse is a drug-device therapeutic modality platform consisted of proprietary intratumoral electroporation (EP) delivery devices (the ‘OncoSec Medical System (OMS) Electroporation Device’ or ‘OMS EP Device’) and a proprietary DNA plasmid that triggers transient expression of target protein in cells. The OMS EP Device is designed to deliver plasmid DNA-encoded drugs directly into a solid tumor and promote an immunological response against cancer. The OMS EP Device can be adapted to treat different tumor types, and consists of an electrical pulse generator, a reusable handle and disposable applicators. The company’s lead product candidate is a DNA-encoded interleukin-12 (IL-12) called tavokinogene telseplasmid (TAVO). The OMS EP Device is used to deliver TAVO intratumorally, with the intention of reversing the immunosuppressive microenvironment in the treated tumor. The activation of the appropriate inflammatory response can drive a systemic anti-tumor response against untreated tumors in other parts of the body. In 2017, the company received Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for TAVO in metastatic melanoma, which could qualify TAVO for expedited FDA review, a rolling Biologics License Application review and certain other benefits. The company’s focus is to pursue its study of TAVO in combination with KEYTRUDA (pembrolizumab) in melanoma and triple negative breast cancer (TNBC). Clinical Programs Lead Product Candidate: TAVO The company’s lead product candidate, TAVO, is a drug-device combination. The drug consists of a plasmid construct called tavokinogene telseplasmid with plasmid DNA-encoded, IL-12, and is delivered into a tumor using the company’s proprietary EP Device. The company’s clinical data indicates that the in vivo gene transfer of plasmid DNA-encoded IL-12 using EP is well-tolerated and anti-tumor activity has been observed after a single cycle of treatment. Importantly, regression in distant, non-injected/non-electroporated lesions has also been observed (abscopal effect) in different solid cancers. Clinical Pipeline KEYNOTE-695 Study (Ongoing) The KEYNOTE-695 study is a Phase 2b, open-label, single-arm, multi-center study of TAVO-EP in combination with an intravenous anti-PD-1 (program cell-death-1) antibody, Merck’s KEYTRUDA, in patients with unresectable locally advanced or metastatic melanoma and confirmed progression on immediate prior anti-PD1 therapy. The KEYNOTE-695 study completed enrollment of the original patient cohort (105 patients) in December of 2020 during the Covid pandemic, approximately half of the cohort was enrolled. The study is enrolling approximately 25 additional patients in an expansion cohort in Australia, Canada and Europe to gain patient experience with the OMS EP Device (using the GenPulse generator and Series 3 Applicator). The data from this study will support filing for accelerated approval with the FDA in 2022. KEYNOTE-695 is a registration directed clinical trial. In order to be eligible for accelerated approval, the TAVO / KEYTRUDA combination must treat a serious condition and provide a meaningful advantage over available therapies. Prior to the commencement of the study, the company reviewed the patient inclusion and progression criteria, and other study requirements with FDA. In light of this review, it defined the patient population to be enrolled in KEYNOTE-695 to include only those patients who have definitively progressed on prior anti-PD-1 checkpoint therapy. OMS-102 (Completed) OMS-102 was an open-label, multi-center, Phase 2 trial of TAVO and KEYTRUDA (pembrolizumab) in patients with advanced, metastatic melanoma. In August 2015, the company enrolled the first patient in its Phase 2 investigator-sponsored clinical trial led by the clinicians at the University of California, San Francisco (UCSF). Huntsman Cancer Institute in Utah was the second clinical site. The primary endpoint of this study was to assess the anti-tumor efficacy of the combination of TAVO and KEYTRUDA in patients with stage III/IV metastatic melanoma whose tumors are characterized by low frequency of CD8+/PD-1+/CTLA-4+ TILs (tumor infiltrating lymphocytes). The primary endpoint of the study was best overall response rate by RECIST of the combination regimen. Recent data suggests that patients whose tumors are lacking TILs or CD8+ T-cells at the tumor margin or generally have a low frequency of CD8+/PD-L1+/CTLA-4+ TILs are unlikely to respond to anti-PD-1 therapies, such as KEYTRUDA, while tumors with a frequency of CTLA-4+/PD-L1+/CD8+ >20% in the tumor are likely to have a clinical benefit. Therapies, such as TAVO, that promote TIL generation and PD-L1 (programmed death-ligand-1) positivity play an important role in augmenting the clinical efficacy of the anti-PD1/PD-L1 agents. OMS-100 (Completed) OMS-100 was an open-label Phase 2 trial of TAVO monotherapy in patients with metastatic melanoma. In December 2014, the company released top-line six-month data from a Phase 2 repeat dose trial of TAVO in patients with stage III/IV metastatic melanoma. The company presented final data at the Melanoma Bridge Conference in 2018. This study is locked with the data collected at 6 clinical centers. Thirty (30) patients with stage III/IV melanoma received up to four cycles of TAVO delivered by EP on days one, five and eight of each 12-week cycle. Phase 2 Investigator-Initiated Neoadjuvant Study In August 2020, the company commenced an investigator-initiated Phase 2 study conducted by the H. Lee Moffitt Cancer Center and Research Institute and the University of South Florida Morsani College of Medicine to evaluate TAVO as neoadjuvant treatment (administered before surgery) in combination with intravenous OPDIVO (nivolumab) in up to 33 patients with operable locally/regionally advanced melanoma. This investigator-initiated Phase 2 study has been designed to evaluate whether the addition of TAVO can increase the published anti-tumor response observed with monotherapy OPDIVO, an anti-PD-1 checkpoint inhibitor, in patients with locally/regionally advanced melanoma prior to surgical resection of tumors. This study is enrolling. Triple Negative Breast Cancer (TNBC) KEYNOTE-890 Study (Ongoing) KEYNOTE-890 is a Phase 2, open-label, single-arm, multi-center study of TAVO in combination with an intravenous anti-PD-1 antibody, Merck’s KEYTRUDA, in patients with histologically confirmed diagnosis of inoperable locally advanced or metastatic TNBC who have received at least one prior line of approved systemic chemotherapy or immunotherapy. In collaboration with Merck, KEYNOTE-890, Cohort 1 completed enrollment in early 2020. Enrollment in Cohort 2 began in the first quarter of 2021. The company previously provided interim data from Cohort 1 in December 2019 on the first group of patients enrolled from this study at the San Antonio Breast Cancer Symposium (SABCS). The fully enrolled Cohort 1 efficacy, durability, and safety data will be presented at SABCS the week of December 6, 2021. Based on the outcome of the study and feedback from FDA, the company amended the KEYNOTE-890 clinical protocol to include TAVO in combination with KEYTRUDA plus chemotherapy to evaluate the safety and efficacy of the combination in treatment-naïve patients with inoperable locally advanced or metastatic triple negative breast cancer, Cohort 2. The study is a Phase 2 open-label, single-arm, multicenter study in the United States and Australia. OMS-140 (Completed) OMS-140 is a Phase 2, monotherapy biomarker study in patients with advanced or metastatic TNBC. The study is being conducted at Stanford University and is designed to assess whether TAVO increases TNBC tumor immunogenicity by driving a pro-inflammatory cascade that leads to increases in cytotoxic tumor infiltrating lymphocytes (TILs). The presence and number of TILs is thought to be a key requirement for promoting the anti-tumor activity of anti-PD-1. By driving cytotoxic immune cells into the tumor, TAVO could be used in combination with checkpoint blockade therapies, which have reported some, but limited, activity in TNBC. Preliminary data was presented at the SABCS annual meeting in 2018 and enrollment in this trial (n=10) is complete. The clinical observations from this study prompted the company to conduct KEYNOTE-890, which is underway. Squamous Cell Carcinoma Head and Neck Cancer (SCCHN) OMS-131 (Ongoing) OMS-131 is an investigator-initiated Phase 2 clinical trial conducted by the University of California San Francisco Helen Diller Family Comprehensive Cancer Center. This study stopped enrolling and amendments to the protocol are under consideration. OMS-131, also referred to as the ‘TRIFECTA’ study, was formed from the clinical observations from a 2017 pilot study of TAVO in head and neck cancer patients, which demonstrated clinical and biological results, including evidence of synergy between TAVO and PD-1 antibodies in the disease. Roswell Park Comprehensive Cancer Center The company has an ongoing research collaboration with Roswell Park Comprehensive Cancer Center (Roswell Park) to evaluate the use of Roswell Park’s intravital microscopy (IVM) and TAVOPLUS (enhanced IL-12 DNA-plasmid), in combination with the company’s APOLLO EP generator in preclinical studies. Duke University The company has an ongoing research collaboration with Duke University’s Center for Applied Therapeutics (Duke University) to evaluate TAVOPLUS in combination or sequenced with a HER2-plasmid vaccine administered the company’s APOLLO EP generator in preclinical studies. Visceral Lesion Applicator The company is developing its next-generation intratumoral delivery device and applicators, including advancements toward prototypes, pursuing discovery research to identify other product candidates that, in addition to IL-12, can be encoded into propriety plasmid-DNA, delivered intratumorally. Specifically, the company is developing a new, propriety technology to potentially treat liver, lung, bladder, pancreatic and other difficult to treat visceral lesions through the direct delivery of plasmid-based IL-12 with a new VLA (visceral lesion applicator). The VLA has been designed to work with low voltage EP generators. Moving forward, the company sees significant opportunity to leverage this innovative technology to secure new partnerships that may allow the company to expand its capabilities and drive shareholder value. Throughout 2019 and 2020, the company has successfully completed five large animal studies and aims to bring the VLA into the clinic during 2023. OMS Electroporation Device The company’s EP delivery system consists of an electrical generator, a reusable applicator handle and disposable tips. While the extent of membrane permeabilization depends on various electrical, physical, chemical, and biological parameters, research with EP delivery has demonstrated an improvement in cellular uptake of chemical molecules, such as chemotherapeutic agents (e.g., bleomycin and cisplatin), and nucleic acids (e.g., DNA and RNA). The company’s OMS EP Devices are designed to create favorable conditions to deliver plasmid DNA encoding immunotherapeutic cytokines directly into cells of the tumor microenvironment. The cytokine-encoding plasmid is first injected into the tumor. A needle-electrode array then delivers the electrical pulses produced in the pulse generator. The company’s lead product candidate, TAVO, consists of a plasmid construct encoding the proinflammatory cytokine IL-12 that is injected into the tumor and delivered into the tumor cells through in vivo electroporation using its OMS EP Device. The company is also researching other DNA-encoded, immunologically-active molecules, with an aim of developing additional immunotherapeutic drugs that, when delivered using the company’s OMS EP Device, may be capable of breaking the immune system’s tolerance to cancer. Manufacturing and Supply The company relies upon a small number of suppliers and manufacturers for its clinical activities. For manufacturing and distributing, the company uses Cryosite, PCI, Richter-Helm Biologics, VGXI, Baxter Oncology GmbH, SGS, Minnetronix and EG Medacys, which collectively account for approximately 90% of clinical materials and EP systems support and materials. In addition, for combination trials, the company relies exclusively on one supplier of the non-company-owned product used in the trial, such as its reliance upon Merck for the supply of KEYTRUDA in the KEYNOTE-695 and KEYNOTE-890 studies. Intellectual Property As of October 2021, the company owned 66 issued patents (5 U.S. and 61 foreign) and 94 pending patent applications (13 U.S. and 81 foreign). The company is prosecuting pending patent applications in various jurisdictions. The company has issued patents in the U.S., Europe, and Japan with claims directed to cytokine-based intratumoral immunotherapies in combination with a checkpoint inhibitor. The Japanese patent was issued May 7, 2021. U.S. Patent 11071860, with claims directed to electroporation systems and devices having enhanced safety features, including novel monitoring and crowbar trigger circuitries was issued on July 27, 2021. Japanese patent 6860497 directed to various adaptive electroporation systems and delivery assemblies was issued on March 30, 2021. In addition, the company has licensed intellectual property rights that allow it to use certain EP technology to deliver DNA-based cytokines as an immunotherapy, as well as catheter-based delivery devices. From these in-licensed portfolios, the company has access to 79 issued U.S. and foreign issued patents (6 from USF, 16 from Gaeta Therapeutics, and 57 from Inovio Pharmaceuticals, Inc. (Inovio)) and 13 U.S. and foreign pending patent applications (2 from USF, 3 from Gaeta Therapeutics, and 8 from Inovio). The company expects to continue to file additional patent applications, if and when appropriate, as its research and development efforts continue. The majority of the patents in its portfolio, including owned and in-licensed patents and fundamental patents directed toward the company’s proprietary technology, expire between 2023 and 2041. The company has previously obtained patent protection through an asset purchase agreement with Inovio covering its original clinical electroporation device. The primary patents providing protection of this original device have expired. However, the company has filed applications, in 2019-2021, on its next generation electroporation devices and applicator handles and the company’s next generation DNA-based cancer immunotherapeutics and will continue to file patent applications this year. In addition, the company has entered into a cross-license agreement for certain electroporation technology with Inovio, including patent protection for some of its clinical electroporation devices (some of which have expired or will soon expire). Under the terms of the agreement, Inovio has granted the company a non-exclusive, worldwide license under certain of its electroporation patents, and in exchange, the company has granted to Inovio an exclusive license to certain of its purchased technology in a limited field of use. Regulation In the United States, the federal Food, Drug and Cosmetic Act, or FDCA, other state statutes and regulations, many of which are administered and enforced by the FDA, govern or influence, among other things, the research, development, verification, validation, clinical testing, manufacturing, storage, record-keeping, approval, labeling, promotion, marketing, distribution, post-approval monitoring and reporting, sampling, import and export of product candidates, such as the company. The U.S. federal and state healthcare laws and regulations that impact the company’s business include, among others, the laws and regulations administered and enforced by the FDA, including the FDCA, and other federal statutes and regulations; the federal Patient Protection and Affordable Care Act as amended by the Health Care and Education Reconciliation Act, referred to collectively as the Affordable Care Act; the federal Anti-Kickback Statute; the federal false claims laws; the federal Health Insurance Portability and Accountability Act of 1986, as amended by the federal Health Information Technology for Economic and Clinical Health Act; and analogous state and foreign laws and regulations, such as anti-kickback and false claims laws. Research and Development Expenses The company’s research and development expenses were $34.1 million during the year ended July 31, 2021. History The company was founded in 2008. It was incorporated under the laws of Nevada in 2008. The company was formerly known as Netventory Solutions Inc. and changed its name to OncoSec Medical Incorporated in 2011.
