Advaxis (ADXS) is a small clinical-stage biotech producing and developing cancer immunotherapy products based on its proprietary Lm Technology. The technology uses bioengineered live attenuated Listeria monocytogenes (Lm) bacteria. It is said that Adraxis therapeutics cancer immunotherapy agents are the first to generate cancer fighting T cells against cancer antigens in early testing. They could also neutralize myeloid-derived suppressor cells (MDSCs), which protect the tumor microenvironment from immunologic attack and contribute to tumor growth.
Advaxis Lm Technology™ utilizes live attenuated Listeria monocytogenes (Lm) bioengineered to produce and deliver tumor antigen/adjuvant fusion proteins within antigen presenting cells with the goal of generating strong, T-cell-mediated immunity. See later in the article how this technology is being used on Advaxis product known as ADXS-NEO, which will be developed by Amgen.
Advaxis’ lead Lm Technology™ immunotherapy, AXAL, targets human papillomavirus (HPV)-associated cancers and is in clinical trials for three potential indications:
Phase 3 in invasive cervical cancer,
Phase 2 in head and neck cancer, and;
Phase 2 in anal cancer.
The FDA has granted AXAL orphan drug designation for each of these three clinical settings, as well as a Special Protocol Assessment for the Phase 3 AIM2CERV trial in patients with high risk, locally advanced cervical cancer.
AXAL has also been classified as an advanced therapy medicinal product for the treatment of cervical cancer by the European Medicines Agency’s Committee for Advanced Therapies.
Advaxis has two additional immunotherapy products: ADXS-PSA in prostate cancer and ADXS-HER2 in HER2 expressing solid tumors, in human clinical development.
In the NEWS
Internal Products’ News
Results from Advaxis Phase 2 “window of opportunity” clinical study of AXAL (axalimogene filolisbac in patients with late-stage HPV-associated oropharyngeal cancer (HPVOPC) met its stage 1 primary objective and is advancing into the second stage of the clinical study.
The clinical study was for of patients with stage I-IV HPVOPC who are to undergo ablative trans-oral robotic surgery (TORS) as a preoperative treatment. The clinical study leverages the five- to six-week period between diagnosis and the robotic surgery, making it possible to analyze and compare the tumor microenvironment as well as peripheral blood samples collected before and after AXAL treatments.
The goal of the study: The clinical study is designed to show that AXAL is highly immunogenic and worth further investigation. High immunogenicity will be considered positive if the overall rate of vaccine-induced T-cell responses is 75 percent or more.
About the Positive Results
Andrew G. Sikora, MD, PhD, of the Bobby R. Alford Department of Otolaryngology-Head and Neck Surgery at Baylor College of Medicine who is the study’s lead investigator said, that the TNFα and IFN-γ response in stage 1 confirmed that the clinical study has already met the target for the overall rate of vaccine-induced T-cell response, which offer the green light for the product to move to stage 2. These results, added to the prior published data that demonstrated increased T-cell infiltration of the malignant cells in a significant number of AXAL treated patients provide the confidence needed for the trial to move forward with the definitive evaluation of the product’s immunogenicity.
The positive results of AXAL (Axalimogene Filolisbac) Advaxis’ lead drug test are good news for the firm, for its technology and its pipeline products. If the drug passes all the trials, it will be treating oropharyngeal cancer patients.
There are also around 12,000 new cases of HPV-associated head and neck cancer per year and the HPV-associated head and neck cancer is growing fastest in developed countries like the U.S.
Why Treating oropharyngeal cancer with AXAL is important?
While patients may achieve a long-term survival with standard treatments comprising surgery, radiation and chemotherapy, these treatments can cause changes in the physical appearance of people. In addition to being associated with significant short and long-term toxicities which may interfere with salivary gland function, affecting people’s taste, smell, and addition to diminishing their ability to swallow.
Separately, in a completed randomized Phase 2 study in recurrent/refractory cervical cancer, AXAL showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the company’s Lm Technology.
Recent NEWS About Collaboration
Amgen (AMGN) and Advaxis signed a global agreement for the development and commercialization of Advaxis’ drug ADXS-NEO – a novel, preclinical investigational cancer immunotherapy treatment designed to activate a patient’s immune system to respond against the unique mutations, or neoepitopes, contained in and identified from each individual patient’s tumor.
This collaboration marries Amgen’s expertise in immuno-oncology with Advaxis’ MINE™ (My Immunotherapy Neo-Epitopes) program (read below), which position them to develop a customized approach to cancer treatment.
Amgen receives exclusive worldwide rights to develop and commercialize ADXS-NEO.
Amgen will make an upfront payment to Advaxis of $40 million and purchase $25 million of Advaxis common stock.
Amgen will be fully responsible for funding clinical and commercial activities.
Advaxis will lead the clinical development of ADXS-NEO through proof-of-concept.
Advaxis will retain manufacturing responsibilities
Advaxis will receive development, regulatory and sales milestone payments of up to $475 million and potential high single digit to mid-double digit royalty payments based on worldwide sales.
As a pioneer in the science of using living cells to develop biologic therapeutics, Amgen is seen to be an incredibly strong partner for the development and commercialization of Advaxis’ products.
For ADXS-NEO, DNA from each patient’s primary tumor and/or metastases as well as normal cells, is sequenced and compared to identify mutations in genes coding for potential neo-antigens in the cancer. Advaxis then engineers and manufactures patient-specific Lm-LLO (listeriolysin O) vectors capable of immunizing them against neoepitopes exclusive to their cancer. After the ADXS-NEO infusion, neoepitope peptides corresponding to each patient’s cancer-associated mutations are delivered directly into their antigen presenting cells by Lm-LLO, where they can stimulate cellular immune responses against multiple neoepitopes simultaneously. Clinical trials for ADXS-NEO are expected to begin in 2017.
Advaxis Approaches to Immunotherapy
MINE™ (My Immunotherapy Neo-Epitopes)/ADXS-NEO
MINE™ (My Immunotherapy Neo-Epitopes) and ADXS-NEO are designed to activate a patient’s immune system to respond against the unique mutations, or neoepitopes, contained in each individual patient’s tumor. This strategy, using massive parallel sequencing, eliminates the need for predictive algorithms and enables the development of truly personalized immunotherapies that can be manufactured in a manner that is cost-effective and timely for patients.
MINE™ will evaluate the immunologic and anti-tumor activity of this patient tumor-specific, neoepitope-based immunotherapy. Advaxis and Amgen will use learnings from MINE to identify and target neoepitopes using Lm Technology™ and later develop patient specific immunotherapy constructs that incorporate the neoepitope sequences identified in the patient’s tumor cells. Clinical studies using ADXS-NEO are in development.
Some small companies with strong scientific fundamentals and creativity can take time to begin speeding on the right track. Advaxis, like some other scientifically oriented and creative firms struggled to solve problems that the firm became aware of through negative studies where errors preceded successes. It took time indeed for Advaxis to begin validating its technologies and products. Optimism began to replace pessimism in the scientific arena about this firm’s immunotherapy approach towards treating cancers through promising results. Indeed, preclinical evidence currently suggests that Lm Technology™ immunotherapies are well-equipped to demonstrate a synergistic anti-tumor response with checkpoint inhibitors (e.g., PD-1 and PD-L1 antibodies) and co-stimulatory molecules (e.g., OX40 and GITR agonists).
Based on these successes, Advaxis forged strategic collaborations with the following major biopharmaceutical companies: Amgen (read above), Merck and AstraZeneca.
The firm has licensing agreements with the following firms: Artana Therapeutics, Biocon and Global Biopharma.
Collaborations with Academic Institutions and Foundations comprised: Icahn School of Medicine at Mount Sinai, Brown University Oncology Group, Gynecology Oncology Group (GOG), NRG Oncology, Cancer Therapy Evaluation Program and National Cancer Institute (NCI)
Other Groups include: Radiation Therapy Oncology Group (RTOG) Foundation, Children Oncology Group (COG), City of Hope, Baylor College of Medecine, November Foundation, Prostate Cancer Foundation (PCF), Thomas Jefferson University, UCSF Medical Center and Memorial Sloan Kettering.
Today’s Price: $14.15
Market Cap: $486 M
52-Week Range: $5.21 – $22.20
Total Cash: Around $100 M
Again we say, Advaxis has strong scientific fundamentals and began to validate important immunotherapy approaches that are now on the right track of well-designed and thought clinical trials. After attracting AstraZeneca and Merck, Advaxis has recently attracted Amgen in a clinical collaboration worth over $400 million and royalties in case of approval (see above).
We will be following up on Advaxis’ clinical trial with its immunotherapy cancer drugs.
A take over is not an unlikely possibility.