About Advaxis

Advaxis, Inc., a clinical-stage biotechnology company, focuses on the development and commercialization of Listeria monocytogenes (Lm) Technology antigen delivery products based on a platform technology that utilizes live attenuated Lm bioengineered to secrete antigen/adjuvant fusion proteins. The company focuses on single antigen and multiple antigen delivery products and is in various stages of clinical development. Within the Antigen Presenting Cells, Lm produces virulence factors, which allow survival in the host cytosol and potently stimulate the immune system. Clinical Pipeline The company is conducting or planning clinical studies of Lm Technology immunotherapies in non-small cell lung cancer and other solid tumor types, prostate cancer, and human papilloma virus (HPV)-associated cancers. It is working with, or is in the process of identifying, collaborators, and potential licensees for these programs. The company is mainly concentrating on its disease-focused, hotspot/’off-the-shelf’ neoantigen-directed therapies called ADXS-HOT. ADXS-HOT is a program that leverages the company’s proprietary Lm technology to target hotspot mutations that commonly occur in specific cancer types. ADXS-HOT drug candidates are designed to target acquired shared or ‘public’ mutations in tumor driver genes along with other cancer-associated antigens that also commonly occur in specific cancer types. Pipeline of Product Candidates Disease Focused Hotspot/‘off the shelf’ Neoantigen Therapies (ADXS-HOT) The company is creating a group of immunotherapy constructs for major solid tumor cancers that combines its optimized Lm Technology vector with targets designed to generate potent anti-cancer immunity. The ADXS-HOT program is a series of novel cancer immunotherapies that would target somatic mutations, or hotspots, cancer testis antigens (CTAs) and oncofetal antigens (OFAs). These three types of targets form the basis of the ADXS-HOT program because they are designed to be capable of generating potent, tumor specific, and high strength killer T cells, versus more traditional over-expressed native sequence tumor associated antigens. Various hotspot mutations and OFA/CTA proteins play critical roles in oncogenesis; targeting both at once could significantly impair cancer proliferation. The ADXS-HOT products would combine majority of the potential high avidity targets that are expressed in all patients with the target disease into one ‘off-the-shelf’, ready to administer treatment. The ADXS-HOT technology has an intellectual property (IP) position, with potential protection into 2037, and an IP filing strategy providing for coverage opportunities across multiple disease platforms and combination therapies. In July 2018, the company announced that the U.S. Food and Drug Administration (FDA) allowed the company’s investigational new drug (IND) application for its ADXS-HOT drug candidate (ADXS-503) for non-small cell lung cancer (NSCLC). The Phase 1/2 clinical trial of ADXS-503 is seeking to establish the recommended dose, safety, tolerability and clinical activity of ADXS-503 administered alone and in combination with a KEYTRUDA in approximately 50 patients with NSCLC, in at least five sites across the U.S. ADXS-503 is being evaluated in a Phase 1/2 clinical trial, enrolling patients at five sites. The first two dose-levels with monotherapy in Part A, (1 X108 CFU and 5 X108 CFU) have been completed and Part B and Part C with ADXS-503 (1 X108 CFU) in combination with a checkpoint inhibitor are open to enrollment. The company presented updated clinical data from Part B of the ADXS-503 clinical study at ASCO Annual Meeting 2021. The poster presentation titled ‘A phase 1 study of an off-the-shelf, multi-neoantigen vector (ADXS-503) in patients with metastatic non-small-cell lung cancer (NSCLC) progressing on pembrolizumab as last therapy’ presented data on 10 patients who have been treated with ADXS-503 as an add-on therapy to patients failing pembrolizumab as last therapy with 10 patients evaluable for safety and nine patients evaluable for efficacy. Enrollment in Part B of the ongoing study would continue to further evaluate the clinical benefit and immune effects of adding on ADXS-503 to patients progressing on pembrolizumab. An update of the clinical and translational results is expected to be presented at a medical conference in 2Q2022. The company also entered into an agreement with Columbia University Irving Medical Center in April 2021 to fund a phase 1 clinical study evaluating ADXS-504 in patients with biochemically recurrent prostate cancer. The study started early in 3Q 2021 and it would be the first clinical evaluation of ADXS-504, its off-the-shelf neoantigen immunotherapy drug candidate for early prostate cancer. The phase 1 open-label study will evaluate the safety and tolerability of ADXS-504 monotherapy, administered via infusion, in 9-18 patients with biochemically recurrent prostate cancer, i.e., those with elevation of prostate-specific antigen (PSA) in the blood after radical prostatectomy or radical radiotherapy (external beam or brachytherapy) and who are not receiving androgen ablation therapy. The study would also evaluate if the body’s immune system could control the prostate cancer following treatment with ADXS-504 monotherapy. HPV-Related Cancers The company conducted various studies evaluating axalimogene filolisbac, or AXAL, for HPV-related cancers. AXAL is an Lm-based antigen delivery product directed against HPV and designed to target cells expressing HPV. In June 2019, the company announced the closing of its AIM2CERV Phase 3 clinical trial with AXAL in high-risk locally advanced cervical cancer. It has unblinded the AIM2CERV clinical data generated to date and has no plans to present it at any medical conference as the data set is incomplete and inconclusive. In 2014, the company granted Global BioPharma (GBP), an exclusive license for the development and commercialization of AXAL in Asia, Africa, and the former USSR territory, exclusive of India and certain other countries. GBP is responsible for all development and commercial costs and activities associated with the development in their territories. Other HPV Program Licensing Agreements Biocon Limited, the company’s co-development and commercialization partner for AXAL in India and key emerging markets, filed a Marketing Authorization Application for licensure of this immunotherapy in India. The companies would evaluate next steps regarding potential registration in India. Especificos Stendhal SA de CV (Stendhal), the company’s co-development and commercialization partner for AXAL in Mexico, Brazil, Colombia and other Latin American countries, agreed to pay in support payment towards the expense of AIM2CERV over the duration of the trial, contingent upon the company achieving annual project milestones, pursuant to a co-development and commercialization agreement (the Stendhal Agreement). The company is in arbitration proceedings with Stendhal. Knight Therapeutics Inc. holds an exclusive license to commercialize AXAL in Canada, as well as other product candidates. Personalized Neoantigen-directed Therapies (ADXS-NEO) ADXS-NEO is an individualized Lm Technology antigen delivery product developed using whole-exome sequencing of a patient’s tumor to identify neoantigens. ADXS-NEO is designed to work by presenting a payload of neoantigens directly into dendritic cells within the patient’s immune system and stimulating a T cell response against cancerous cells. In October 2019, the company announced that it has dosed its last patient in Part A, in monotherapy, and does not intend to continue into Part B, in combination with a checkpoint inhibitor. As a result, the company has closed this study. It has completed the clinical study report from Part A of the ADXS-NEO study and the NEO program-IND inactivation request has been submitted to FDA. Prostate Cancer (ADXS-PSA) The company has entered into a clinical trial collaboration and supply agreement with Merck to evaluate the safety and efficacy of ADXS-PSA as monotherapy and in combination with KEYTRUDA, Merck’s anti PD-1 antibody, in a Phase 1/2, open-label, multicenter, dose determination and expansion trial in patients with previously treated metastatic, castration-resistant prostate cancer (KEYNOTE-046). ADXS-PSA was tested alone or in combination with KEYTRUDA in an advanced and heavily pretreated patient population who had progressed on androgen deprivation therapy. At the final data cutoff of September 16, 2019, median overall survival for various patients in the combination arm was 33.6 months (95% CI, range 15.4-33.6 months). This updated median overall survival is an increase from the previous data presented at the American Association for Cancer Research Annual Meeting in April 2019, where median overall survival was 21.1 months in the combination arm. The combination of ADXS-PSA with KEYTRUDA, might be associated with prolonged OS in this population, particularly in patients with unmet medical needs, such as visceral metastasis (16.4 months, range 4.0 - not reached) and those with prior docetaxel (16 months, range 6.4-34.6). The majority of TEAEs consisted of transient and reversible Grade 1-2 chills/rigors, fever, hypotension, nausea and fatigue. The combination of ADXS-PSA and KEYTRUDA has appeared to be tolerated as of October 31, 2020, with no additive toxicity observed. The company presented these new data at the ASCO Genitourinary Cancers Symposium in San Francisco, CA. in February 2020. The company is seeking potential partners regarding opportunities to expand or advance this metastatic castration-resistant prostate cancer program. Other Lm Technology Products Human Epidermal Growth Factor Receptor-2 (HER2) Expressing Solid Tumors ADXS-HER2 is a Lm Technology antigen delivery product candidate designed to target HER2 expressing solid tumors, including human and canine osteosarcoma. ADXS-HER2 has received FDA and European Medicines Agency orphan drug designation (ODD) for osteosarcoma and has received Fast Track designation from the FDA for patients with newly-diagnosed, non-metastatic, surgically-resectable osteosarcoma. In September 2018, the company announced that it had granted a license to OS Therapies, LLC (OS Therapies) for the use of ADXS31-164, also known as ADXS-HER2, for evaluation in the treatment of osteosarcoma in humans. Under the terms of the license agreement, OS Therapies, in collaboration with the Children’s Oncology Group, would be responsible for the conduct and funding of a clinical study evaluating ADXS-HER2 in recurrent, completely resected osteosarcoma. Canine Osteosarcoma In March 2014, the company entered into a definitive Exclusive License Agreement (Aratana Agreement) with Aratana Therapeutics, Inc. (Aratana), where the company granted Aratana an exclusive, worldwide, royalty-bearing license, with the right to sublicense, certain of its proprietary technology that enables Aratana to develop and commercialize animal health products that would be targeted for the treatment of osteosarcoma and other cancer indications in animals. A product license request was filed by Aratana for ADXS-HER2 (also known as AT-014 by Aratana) for the treatment of canine osteosarcoma with the United States Department of Agriculture (USDA). Aratana received communication in December 2017 that the USDA granted Aratana conditional licensure for AT-014 for the treatment of dogs diagnosed with osteosarcoma, one year of age or older. Initially, Aratana plans to make the therapeutic available for purchase at approximately two dozen veterinary oncology practice groups across the United States who participate in the study. Aratana received communication in December 2017 that the USDA granted Aratana conditional licensure for AT-014 for the treatment of dogs diagnosed with osteosarcoma, one year of age or older. Aratana is conducting an extended field study, which is a requirement for full USDA licensure. Initially, Aratana plans to make the therapeutic available for purchase at approximately two dozen veterinary oncology practice groups across the United States who participate in the study. Strategy The company’s strategy is to advance the Lm Technology platform and utilize its capabilities to design and develop an array of cancer treatments. Intellectual Property (IP) The company owns or has rights to various patents and applications, which are owned, licensed from, or co-owned with University of Pennsylvania, Merck, National Institute of Health, and/or Augusta University. The company prosecutes and defends its patents and proprietary technology. Its patents and applications are directed to the compositions of matter, use, and methods thereof, of its Lm-LLO immunotherapies for its product candidates, including AXAL, ADXS-PSA, ADXS-HOT, ADXS-HER2. The company has and might continue to abandon prosecuting certain patents that are not strategically aligned with the direction of the company. The company intends to maintain a coherent and aggressive strategic approach to building its patent portfolio with a focus in the field of cancer vaccines. Issued patents, which are directed to AXAL, ADXS-PSA, and ADXS-HER2 in the United States, would expire between 2020 and 2032. Issued patents directed to the company’s product candidates AXAL, ADXS-PSA, and ADXS-HER2 outside of the United States, would expire in 2032. Issued patents directed to the company’s Lm-based immunotherapy platform in the United States, would expire between 2020 and 2031. Issued patents directed to the company’s Lm-based immunotherapy platform outside of the United States, would expire between 2020 and 2033. The company has pending patent applications directed to its product candidates AXAL, ADXS-PSA, ADXS-HER2, and ADXS-HOT that, if issued would expire in the United States and in countries outside of the United States between 2021 and 2037. It has pending patent applications directed to methods of using of its product candidates AXAL, ADXS-PSA, ADXS-HOT, ADXS-HER2 directed to the following indications and others: prostate cancer and HER2/neu-expressing cancer, that, if issued would expire in the United States and in countries outside of the United States between 2021 and 2037, depending on the specific indications. Government Regulations The company has ODD with the FDA for AXAL for the treatment of anal cancer (granted August 2013), HPV-associated head and neck cancer (granted November 2013); and treatment of Stage II-IV invasive cervical cancer (granted May 2014). It also has ODD with the FDA for ADXS-HER2 for the treatment of osteosarcoma (granted May 2014). History Advaxis, Inc. was founded in 2002.