Good afternoon and welcome. Thank you for joining the WTR insights conference session with Anixa Biosciences, ticker ANIX. I'm Robert Sassoon, Managing Director of Healthcare, Neurosciences, and Special Situations at Water Tower Research. Today, we have the pleasure of being joined by Dr. Amit Kumar, CEO of Anixa. Thank you for being here.
Thank you, Robert. Thank you for having me.
A quick reminder before we start, Anixa's safe harbor statements are available in its latest presentation on its website. Also, this conversation may not be reproduced or transcribed without written approval from Water Tower Research. We welcome your questions throughout today's conversation. Please submit them through the chat, and we'll do our best to address them in a follow-up email or in our follow-up management series report. If you would like to request a meeting with Anixa Biosciences, you can do so through the conference portal, and we will attempt said request. With that, let's begin. Amit, Anixa is currently running two clinical development programs. One, a breast cancer vaccine program targeting the most aggressive form of the disease, triple-negative breast cancer, and the other, a novel CAR- T program targeting late-stage ovarian cancer. You also have a pipeline of preclinical vaccine studies in ovarian, lung, prostate, and colon cancers.
Before we delve into the clinical programs, let me start by asking, given the size of your company, how are you ensuring management bandwidth, expertise, and board oversight don't become bottlenecks? How does the team prioritize between scientific advancement, capital preservation, and hitting near-term milestones?
Thank you for those questions. There are a couple of questions there. First of all, from a standpoint of management bandwidth, we only have a total of four employees. We utilize dozens, if not more people, on our clinical trials through our partnership model, at both the Cleveland Clinic and the Moffitt Cancer Center, as well as a number of consultants that we utilize for various other activities, including larger organizations for manufacturing materials for our clinical trials, as well as fill and finish. Eventually, we'll be bringing on a CRO to help us put together the plan and the execution of the phase II clinical trial for our breast cancer vaccine, which is upcoming. The key point is that all of us are highly dedicated to our programs.
As we've discussed before, many of us have bought significant amounts of our stock on the open market, including myself and our Board Members. Frankly, we all do the work of perhaps two or three employees o ur four-person headcount really is much bigger than ordinarily a four-person headcount. The second question you asked is about prioritizing capital allocation as well as clinical trials and scientific innovation. I'm paraphrasing. I don't remember the exact words you used. From the beginning, our goal had been to not burn a tremendous amount of cash, and we built a business plan and business model based on that underlying fundamental goal.
We wanted to advance our programs, prioritize all of them that we felt were going to create value for our shareholders and value for patients, but do it in a way that was well thought out, with partners that enable us to work in a manner that doesn't require us to burn a tremendous amount of capital. I'd like to say that we've succeeded w e've been able to advance two clinical trials in two big unmet areas, breast cancer as well as ovarian cancer. Both of those clinical trials have produced fantastic results and are producing additional fantastic results. We've been doing that all with very minor burn, and we anticipate that that will continue. By burning very small amounts of cash, we reduce the amount of dilution that is necessary to keep moving a development stage company forward and create greater value for our shareholders.
Thanks for that. Let's turn to those clinical programs you just mentioned, starting with your CAR- T program targeting recurrent ovarian cancer, which uses a novel approach focused on the follicle-stimulating hormone receptor, or FSHR. How does your early clinical data differentiate your construct from competing CAR- T programs targeting solid tumors? What specific efficacy or safety signals would you consider proof of concepts sufficient to advance to a larger trial?
Well, in the CAR- T arena, while there's been success in certain types of leukemia and lymphoma, there has not been any approval in any solid tumor indication. And virtually all of the clinical trials targeting solid tumors have failed, or have been halted, or are not producing good data. There are a couple that are starting to show some interesting efficacy, including ours. I believe, to my knowledge, there are about three that have shown some efficacy, although ours I believe, has shown better efficacy than any of those, even though we've only treated 13 patients to date. I think the most important thing to understand about our program is that we've taken the learnings from all of the failures to design a CAR- T approach that we feel is superior and will be successful.
In the early data that we have so far in the small number of patients, we're starting to see really good clinical results, not as good as we would eventually like, but better than anything else. As we go forward, we anticipate even better results t he key point about our program is that we're utilizing local delivery into the peritoneum for ovarian cancer. We've identified a really good target, follicle-stimulating hormone receptor that you noted, which is unique to ovarian cancer w e believe that our program is going to be successful.
We've demonstrated significant increase in life expectancy for the patients that we're treating. These are patients that are terminally ill, that have a median life expectancy of about 12 weeks, about three months, which is when we get them. We've extended the life expectancy of these patients, many of these patients dramatically, in one case as we've discussed before, to over two and a half years. We have not, at this point, curatively treated a patient yet, but we've dramatically demonstrated significant increase in life expectancy.
You alluded to the early data, which shows most patients surviving significantly beyond expectations for their disease, with one more than two years post-low dose treatment. How is Anixa tracking lira-cel or the CAR-T persistence in the tumor microenvironment? What's your hypothesis for why FSHR targeted T- cells avoid T- cell exhaustion seen in other solid tumor CAR-T?
Yeah. Some of those questions we can't answer yet. We look at biomarkers, we look at scans, CT scans of these patients, laboratory test values as well. Ultimately, our final goal is overall survival. How long are we keeping these patients alive. Frankly, none of the other factors, biomarkers or whatnot, really matter if the patients are dying. In our case, we're just focused on overall survival. Obviously, we would like to have good progression-free survival. Overall survival is the benchmark, is the key point, because obviously that's what's important for patients, that's what's important for physicians and so forth. As far as tumor microenvironment, we do see in our scans that the T- cells that we are delivering infiltrate the tumor t hey do get in there.
In fact, we see this. We call it pseudoprogression, where initially after delivering the T- cells, the tumor scans show that the tumors have expanded. They've expanded not because they're growing, but because T- cells have infiltrated the tumor. If they have, then they're obviously doing some work there a s far as exhaustion, we don't have a lot of data on that yet. We believe that ultimately, the T- cells at higher dosages and additional cohorts that we're going to do, will be able to significantly degrade the tumor.
Persistence, while it is important, may not be absolutely the most important thing. If we can destroy the tumor completely, all the tumor lesions completely, then perhaps the patient is free of the cancer. That's our goal. We are looking at cytokines, which are, as you know, communication messages between immune cells and we're going to be looking at various other things, including persistence, as we go forward.
Got it. Given the approved larger dose escalation for the fifth cohort, and the fact that safety has remained clean so far across the preceding four cohorts that you've been testing, how are you thinking about the dose range most likely to deliver meaningful biological activity and support the next value inflection point? What biomarkers or clinical signals will you use to know when you're approaching the top of the dose-response curve rather than still creating an incremental benefit?
Yeah. Well, we think that we've already demonstrated activity of the T- cells, and that's why, in many cases, we see tumor necrosis, meaning the cells in the tumor are dying. The cancer cells are dying, induced by our T- cells t here are two things that we're going to be doing in the next cohort. One is increasing the dose, as well as utilizing a process called lymphodepletion. That's a process which has been used in the hematological CAR- Ts that have been approved. It's not clear whether that process is necessary in solid tumors, because to date we don't have anything in solid tumors that has been approved. The process involves giving the patient certain chemo agents that dramatically degrade the existing immune cells, including the T- cells.
By doing that, you create some risk for the patient, because the patient becomes susceptible to infections and whatnot for a short period of time. What that also does is it enables the engineered T- cells, the cancer-fighting T- cells that we're delivering, to better engraft and proliferate. This is a living therapy. CAR- T cells are a living therapy, and by introducing them into a situation where they don't have to compete with other T- cells, that you're going to be able to create a much more potent response. We're really looking forward to seeing that data in the next cohort, not only because of the increase in dosage, but also the use of lymphodepletion for preparing the patient for the CAR- T therapy.
As far as biomarkers, as I noted earlier, we look at scans, we look at blood values, we look at things like CA 125. Ultimately, the key point that we are always looking at is overall survival. Can we keep the patient alive? It really doesn't matter what the biomarkers are doing. In fact, in some of our cases, we've had biomarkers, like CA 125 increase, but the patient has lived a lot longer than you'd expect. Ultimately, biomarkers have a value, but eventually, the goal is to just keep people alive.
Got it. Turning to the breast cancer vaccine program, which is a little more advanced than the CAR- T program. For the upcoming phase II program, Anixa has decided to go with the neoadjuvant setting by measuring the standard of care, which is typically KEYTRUDA, as the control group, versus the combination of the standard of care and the vaccine. Why have you chosen to pursue this clinical pathway, and how does this combination affect your target product profile?
Very good question. Stepping back for a second, this vaccine is designed to not only be a therapeutic vaccine, meaning it will target patients who are battling breast cancer at the time, but also a prophylactic or preventative vaccine, which will prevent breast cancer occurrence or recurrence. We've chosen to go into the neoadjuvant setting for practical reasons. Typically, a breast cancer patient, once she is diagnosed with breast cancer, usually after a biopsy, the patient is headed towards surgery. Before surgery, the patient receives therapy to try and reduce the tumor burden a t the current time, perhaps, I believe the most common standard of care therapy is KEYTRUDA . KEYTRUDA is a checkpoint inhibitor. It maintains the activity of T- cells, native T- cells as well as engineered T- cells.
Since our vaccine induces the creation of cancer-fighting T- cells, antigen-specific cancer-fighting T- cells, and KEYTRUDA maintains their activity we believe that the combination will be synergistic. Now, in phase I, one of the cohorts of patients that we wanted to test was patients who got KEYTRUDA along with the vaccine. The purpose of that in the phase I trial was not necessarily to see efficacy, because it's a small number of patients that we tried and a very short duration. The goal there was to determine if the combination of KEYTRUDA and vaccine created intolerable side effects. KEYTRUDA, while it is used, it's a very successful drug, it does create very difficult side effects for the patient. Combinations of KEYTRUDA with other things have shown even worse side effects, and we wanted to see if our vaccine did that.
Fortunately, I'm happy to report that our vaccine with KEYTRUDA did not increase the side effect profile. We are able to use the combination in this trial. To your point, we're going to be testing the vaccine along with KEYTRUDA relative to just a KEYTRUDA control, which is standard of care. Because it's neoadjuvant, meaning pre-surgery, we should be able to see some results relatively quickly, and that's the goal. With regard to target product profile, we anticipate that this vaccine as it goes through the clinical trials and various approvals, will initially be targeting therapeutic applications. People who have cancer, who have been recently diagnosed with cancer, or people who have gone through their journey and still have residual disease.
After that, we anticipate it'll be utilized for recurrence prevention, people who've already had cancer but at a higher probability of recurrence. Ultimately, the goal is a preventative or prophylactic vaccine that can be given to women who've never had breast cancer to prevent the onset of breast cancer. It'll be a stepwise process, and the first step is this neoadjuvant trial that we're going to be doing.
Right. By giving all that, do you see this neoadjuvant KEYTRUDA setting as the primary commercial strategy for Anixa rather than a monotherapy? How does it align with your long-term goal of developing the vaccine as a prophylactic?
Yeah. We do see the neoadjuvant therapeutic setting as the first target. Eventually, we will evaluate this vaccine. In the phase I trial in most of the patients, it was given as a solo agent. Eventually, we will evaluate this on a larger number of patients as a solo agent, especially for the prophylactic situation. Because in the prophylactic situation, you're giving the vaccine to patients who are not sick. If you're giving it to healthy patients, then you don't want to induce really bad side effects.
The phase I showed that as a solo agent the only real side effect was irritation at the site of injection. It was rock-solid safe. If you have to give it as a combination with something like KEYTRUDA for preventative or prophylactic applications, it's just not going to fly because KEYTRUDA will cause tremendously difficult side effects for the patient. It will have to be eventually utilized as a solo agent for prophylaxis.
Some argue that the landscape for cancer vaccines is becoming a little crowded with mRNA-based personalized approaches, such as Moderna and Merck's neoantigen vaccines. How does Anixa's off-the-shelf retired protein approach provide a superior value proposition in terms of cost, patient access, and clinical prevention compared to those personalized therapies?
Yeah. mRNA vaccines have created a lot of excitement. That being said, the only mRNA vaccine that have been approved are the vaccines for the COVID virus, which is obviously not a cancer vaccine. While there has been some interesting and positive clinical studies in these personalized mRNA vaccines studies, there have been some epic failures as well in phase III trials. It's not clear exactly where that's going to go. The process of utilizing an mRNA vaccine is complex, and in many ways, sometimes even more complex than autologous CAR- T, which is another very complex process. In the vaccine arena, our vaccine is a typical peptide vaccine. It comes in a small bottle, it sits on the shelf, and it'll be injected in patients as they come in.
An mRNA vaccine requires sampling the tumor, eventually doing a sequencing of the whole tumor, identifying, utilizing now AI to identify specific sequences that could be immunogenic, and then creating those specific mRNA sequences in a custom fashion for every single patient, and then providing them the customized vaccine. That's a very burdensome process, especially for prophylaxis. There are some theories and some thoughts that eventually, after some years and years of evaluating mRNA vaccines for cancers, we might be able to identify specific sequences that could be generally used as a vaccine and as a non-personalized, off-the-shelf vaccine.
We are many, many years away from that. The cost of a mRNA vaccine going through a personalization process is hundreds of thousands of dollars, takes a tremendous amount of time, whereas our vaccine will be sitting on the shelf and be ready for injection for delivery to a patient when that patient is ready.
Great. Thank you for that information. Now, Anixa's collaborations with Cleveland Clinic and Moffitt Cancer Center have helped to de-risk the early development. How are you thinking about phase II and beyond, specifically the path toward big pharma partnerships versus potential spin-outs? Can you clarify for us how IP ownership of Anixa and Anixa's retained economics, for example, milestones and royalties, are structured with these institutions as you enter that next phase?
Yeah. I'm glad you highlighted our partnerships because it underscores a couple of key points, one of which we discussed earlier. Our headcount is only four people, but we have dozens of people at the Cleveland Clinic and the Moffitt Cancer Center working on our projects. We leverage their expertise, their infrastructure, and the world-class scientists that exist at both of these organizations. Second thing that those partnerships underscore is that our clinical trials are being done at those facilities. Both Cleveland Clinic and the Moffitt Cancer Center are amongst the top hospital systems in the world. One of the key attributes of our strategy was that, even as a small company, we wanted to do our clinical trials at the top places in the United States.
There are many small, young companies that are resource-limited that will do trials in third-world nations or other places where it's cheap and the rigor is perhaps not as great as in the United States. We strategically decided that we were not going to do that. We were always going to work with the top places so the credibility of the trial results would be very high. That's been incredible. Those partnerships have been incredible for us. Going forward, we will also establish partnerships with pharmaceutical companies for commercialization.
Again, the goal here is not to create or rebuild infrastructure that already exists in the industry. We don't have big manufacturing facilities. We don't have big sales, marketing, distribution, customer support, but pharma companies do, and they're looking for additional products to push through their infrastructure, and we want to eventually get to a point where we can structure those alliances. I think I answered all the questions you had in that.
I think you did.
Maybe I may have missed one or two. I don't remember.
Well, maybe there'll be a question that we'll follow up with after this.
Okay
Conversation. Can you walk us through Anixa's key catalysts over the next 12 months-18 months that investors should have on their radar?
The next 12-18 months is going to be very important for Anixa. We will continue the data release for all of our additional CAR- T patients. At the current time, we have essentially nine more patients that we will be treating as we go into the additional cohorts. We'll be releasing that data. Excuse me. As I noted earlier, we anticipate the increased dosage as well as the lymphodepletion to have a significant impact on those patients. On the breast cancer vaccine, we anticipate during that 12-18-month period, we will have begun the phase II trial, and we will have some initial data. Typically, for valuation metrics for young companies, when you start showing efficacy in a phase II trial, that's often the point where the valuation dramatically increases. We're looking forward to that.
I think, even though the CAR- T trial is a phase I, we are already seeing efficacy, and we're treating patients and extending their lives. If that trend continues, then I believe valuation will be driven dramatically higher, as well as efficacy, if we are able to see that on the phase II breast cancer trial. Those are the two major things. We're also doing a number of other projects that I can't discuss right now that we'll be reporting on. Obviously, we're prosecuting aggressively our intellectual property on all of these programs. Robert, I just remembered the one question from the previous group of questions that I did not answer, and that was.
Go ahead.
What are the economics of the licensing agreements on both of these products. In both cases, the academic institution where the product was developed, in one case, the Cleveland Clinic, in the other case, The Wistar Institute, which is where the CAR- T was developed, we have agreements to provide some very modest milestone payments, as well as some very modest royalties. As people can see from our burn rate, which is very modest, we've structured those deals so that most of our capital goes into R&D as opposed to royalties and milestone payments.
Right. Final question, what do you believe investors are still underappreciating most about Anixa's story today?
I think the main thing is that investors don't know about us. The company was originally an electronics company that was founded in the 1980s, and I became CEO in 2017 and repositioned the company as a biotech company. We've only been in the biotech world for about seven or eight years, and we've not done a lot of banking transactions. We've done one major financing in 2021. Because of our burn and because of support that we're getting from non-dilutive capital on our programs, we've not had to raise a tremendous amount of money. As a result, Wall Street really doesn't know that much about us. Now that we're demonstrating really positive and promising clinical results, our goal is to go out and tell our story and increase our profile on the Street.
That's one of the reasons where Water Tower Research is helping us. As we go forward, we believe that people will really start recognizing that, number one, we've got programs that are incredibly valuable. Number two, we've built the company in a way that hasn't created a lot of overhang, like warrants and preferred stock, which has been, unfortunately, the cause of toxicity for many other companies, regardless of how good their programs are. We believe as we go forward and people start getting interested again in the biotech sector, that we will be one of the recognized companies.
We wish you all the success there. Thank you, Dr. Amit Kumar, for a great discussion.
Thank you, Robert, for having me.