Anixa Biosciences (ANIX) Risk Analysis

CAR-T, vaccines and other immuno-therapy technologies are being used by third parties in clinical trials for which we are collaborating or in clinical trials which are completely independent of our development programs. We have little to no control over the conduct of those clinical trials. If serious adverse events occur during these or any other clinical trials using technologies similar to ours, the FDA and other regulatory authorities may delay our clinical trial, or could delay, limit or deny approval of our product candidates or require us to conduct additional clinical trials as a condition to marketing approval, which would increase our costs. If we receive regulatory approval for any product candidate and a new and serious safety issue is identified in connection with clinical trials conducted by third parties, the applicable regulatory authorities may withdraw their approval of our products or otherwise restrict our ability to market and sell our products. In addition, treating physicians may be less willing to administer our products due to concerns over such adverse events, which would limit our ability to commercialize our products.

We may experience difficulties in patient enrollment in our clinical trials for a variety of reasons. The timely completion of clinical trials in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of patients who remain in the study until its conclusion. The enrollment of patients depends on many factors, including: - the patient eligibility criteria defined in the clinical trial protocol;   - the size of the patient population required for analysis of the trial's primary endpoints;   - the proximity of patients to the study site;   - the design of the clinical trial;   - our ability to retain clinical trial investigators with the appropriate competencies and experience;   - our ability to obtain and maintain patient consents;   - the risk that patients enrolled in clinical trials will drop out of the clinical trials before completion; and   - competing clinical trials and approved therapies available for patients. In particular, our Phase 1 CAR-T ovarian cancer clinical trial is enrolling patients with late-stage ovarian cancer who have failed conventional treatment, and are willing and able to be treated at Moffitt. Our Phase 1a breast cancer vaccine clinical trial is enrolling patients who have undergone standard of care treatment for TNBC. Our Phase 1b breast cancer vaccine clinical trial is enrolling healthy women who, as a result of, among other things, testing positive for the BRCA1, BRCA2 or PALB2 gene mutations which are leading predictors of future incidence of breast cancer, have elected to have prophylactic mastectomies. Our Phase 1c breast cancer vaccine clinical trial is enrolling post-operative TNBC patients who have residual disease following neoadjuvant chemo-immunotherapy and are being treated with pembrolizumab (Keytruda). These potential trial participants must be willing and able to undergo treatment at the Cleveland Clinic. Our clinical trials will compete with other companies' clinical trials for product candidates that are in the same therapeutic areas as our product candidates, and this competition will reduce the number and types of patients available to us, because some patients who might have opted to enroll in our clinical trials may instead opt to enroll in a trial being conducted by one of our competitors. We expect to conduct our clinical trials at the same clinical trial sites that some of our competitors may use, which will reduce the number of patients who are available for our clinical trial in these clinical trial sites. Moreover, because our product candidates represent a departure from more commonly used methods for cancer treatment, potential patients and their doctors may be inclined to use experimental therapies that use conventional technologies, such as chemotherapy and antibody therapy, rather than enroll patients in our clinical trials. Patients may also be unwilling to participate in our clinical trials because of negative publicity from adverse events in the biotechnology or gene therapy industries. Delays in patient enrollment may result in increased costs or may affect the timing or outcome of our planned clinical trials, which could prevent completion of the clinical trials and adversely affect our ability to advance the development of our ovarian cancer CAR-T therapy and our breast cancer vaccine.

We have limited human clinical data from our breast cancer vaccine and our CAR-T ovarian cancer therapeutic, and we have not initiated clinical trials for our ovarian cancer vaccine and we may not be able to commence clinical trials on the time frames we expect. Further, our new vaccine research programs in high-incidence cancers of the lung, colon and prostate are in the early discovery stage, and have generated no data to date. As our pre-clinical stage product candidate has only been tested in animals and our clinical stage candidates currently have limited human data, we face significant uncertainty regarding how effective and safe they will be in human patients and the results from pre-clinical studies may not be indicative of the results of clinical trials. Pre-clinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in pre-clinical studies and clinical trials have nonetheless failed to obtain marketing approval for their products. Even if clinical trials are successfully completed, the FDA or foreign regulatory authorities may not interpret the results as we do, and more clinical trials could be required before we submit our product candidates for approval. To the extent that the results of our clinical trials are not satisfactory to the FDA or foreign regulatory authorities for support of a marketing application, approval of our product candidates may be significantly delayed, or we may be required to expend significant additional resources, which may not be available to us, to conduct additional clinical trials in support of potential approval of our product candidates.

CAR-T therapies function through the binding of a genetically engineered killer T cell to a cancer cell. However, these engineered T cells destroy the cell they are bound to whether it is a cancer cell or a healthy cell. Therefore, the engineered T cells must be designed to only bind to either cancer cells or other target cells to minimize toxicity. Our CAR-T technology relies on the natural affinity of FSH to FSH-Receptor. Research by others has shown that in women the FSH-Receptor protein is found on ovary cells and generally in no other healthy tissue, and therefore, we engineer our T cells with FSH. However, as the research in this field is still new, we cannot guarantee that there is no FSH-Receptor on any other healthy tissue in the human body.

CAR-T product candidates represent a relatively new field of cellular immunotherapy. Advancing this novel and personalized therapy creates significant challenges for us, or a partner, including: - obtaining regulatory approval, as the FDA and other regulatory authorities have limited experience with commercial development of T cell therapies for cancer;   - sourcing clinical and, if approved, commercial supplies for the materials used to manufacture and process our product candidates;   - developing a consistent and reliable process, while limiting contamination risks, for engineering and manufacturing T cells ex vivo and infusing the engineered T cells into the patient;   - educating medical personnel regarding the potential benefits, as well as the challenges, of incorporating our product candidates into their treatment regimens;   - establishing sales and marketing capabilities upon obtaining any regulatory approval to gain market acceptance of a novel therapy; and   - the availability of coverage and adequate reimbursement from third-party payors for our novel and personalized therapy. Our inability to successfully develop CAR-T cell therapies or develop processes related to the manufacture, sales and marketing of these therapies would adversely affect our business, results of operations and prospects.

The development of preventive and therapeutic cancer vaccines is difficult, with very few cancer vaccines successfully reaching the market. The only vaccines shown to be effective in preventing cancer have been vaccines against cancer causing agents, not the cancer itself. Vaccines work by exposing a benign form of a disease agent to an individual's immune system. The immune system identifies the agent and learns to attack and destroy it, retaining a memory of the agent so the immune system knows to react quickly if an individual is exposed to the disease agent months or years later. Most vaccines attack pathogens, such as viruses and bacteria. The immune system is better able to assail these agents because they come from outside the body. Cancer, however, is caused by aberrant cells that arise out of our resident cells, which can make it difficult for our immune system to find the diseased cells, especially as advancing age weakens our immune system. Once these aberrant cells gain critical mass, they become cancer.

We are in the early discovery stage of developing vaccines against high-incidence malignancies such as lung, colon and prostate cancers, in the pre-clinical stage of developing our ovarian cancer vaccine technology and in the clinical stage with our CAR-T therapeutic technology and with our breast cancer vaccine technology. Our ability to generate revenue depends in large part on our ability, alone or with partners, to successfully complete the development of, obtain the necessary regulatory approvals for, and commercialize, product candidates. We do not anticipate generating revenues from sales of such products for the foreseeable future. Our ability to generate future revenues from product sales of our technologies depends heavily on our success in: - progressing our discovery stage programs into pre-clinical testing;   - progressing our pre-clinical programs into human clinical trials;   - completing requisite clinical trials through all phases of clinical development of our product candidates;   - seeking and obtaining marketing approvals for our product candidates that successfully complete clinical trials, if any;   - launching and commercializing our product candidates for which we obtain marketing approval, if any, with a partner or, if launched independently, successfully establishing a manufacturing, sales force, marketing and distribution infrastructure;   - identifying and developing new product candidates;   - establishing and maintaining supply and manufacturing relationships with third parties;   - maintaining, protecting, expanding and enforcing our intellectual property; and   - attracting, hiring and retaining qualified personnel. Because of the numerous risks and uncertainties associated with biologic and pharmaceutical product development, we are unable to predict the likelihood or timing for when we may receive regulatory approval of our product candidates or when we will be able to achieve or maintain profitability, if ever. If we are unable to establish a development and or commercialization partnership, or do not receive regulatory approvals, our business, prospects, financial condition and results of operations will be adversely affected. Even if we or a partner obtain the regulatory approvals to market and sell one or more of our product candidates, we may never generate significant revenues from any commercial sales for several reasons, including because the market for our products may be smaller than we anticipate, or products may not be adopted by physicians and payors or because our products may not be as efficacious or safe as other treatment options. If we fail to successfully commercialize one or more products, by ourselves or through a partner, we may be unable to generate sufficient revenues to sustain and grow our business and our business, prospects, financial condition and results of operations will be adversely affected.