At the precipice of every great company is a near-insurmountable competitive advantage, like Coca-Cola's (NYSE:KO) "secret recipe" or Apple's (NASDAQ:AAPL) insatiable focus on fine detail in its consumer products. I think I have found this in Advaxis (NASDAQ:ADXS), an oncology company with an immunotherapy platform that I believe is years ahead of the competition. The proprietary platform suggests Advaxis' valuation could be the biggest anomaly since Celgene two decades ago.
I reached out to the company's Chief Scientific Officer, Dr. Robert Petit, to learn more about the underlying science and the 18-month survival data recently released. To my surprise, he was kind enough to answer all of my questions and even allowed me to publish our discussion for the benefit of other shareholders. The following is a transcript of my interview with Advaxis' CSO, Robert Petit. (Bold text represents my questions.) [Minor edits were made to the transcript for publication to Seeking Alpha]
Dr. Petit, thank you for participating in this interview. Before we jump into the questions about Advaxis and the positive data from the 18-month survival data from the Phase 2 study in recurrent Cervical Cancer, for the readers- Could you provide your background, particularly in the immunotherapy space?
Petit: I've been involved in the development of immunotherapy since 1987 when I co-founded an Immunotherapy program in Academia. I always reasoned that the best possible compromise between safety and efficacy would be found by utilizing the body's own immune system to identify and eliminate cancerous cells. For the last 20 years I've been in the Pharmaceutical and Biotech industry working almost exclusively with oncology and immunology clinical development. I have contributed to 5 NDA's (New Drug Application) and BLAs (Biologic License Application) and launched 3 major treatments in Oncology and Immunology. Most recently before joining Advaxis, I was Director of Medical Strategy at Bristol Myers Squibb (NYSE:BMY) and served as the US Medical Lead for Yervoy (ipilimumab), the most recently immunotherapy for cancer approved by the FDA.
Wow, so what prompted you to jump ship to Advaxis- what draws you to the company's immunotherapy platform?
Petit: After we filed the BLA for Yervoy, I started looking across the field trying to identify what the next significant breakthrough could be in immunotherapy. I was not looking for a variation of the first generation of immunotherapies, but I was looking for a technology designed to take this treatment closer to the real promise of immunotherapy that attracted me back in 1987. What I call "A disruptive innovation" in immunotherapy that would hopefully avoid the challenges that can hold back current immunotherapies while retaining the best parts that allowed them to prolong the lives of people with cancer. The more I looked into the Advaxis immunotherapy technology the more intrigued I became as I saw that it has real potential to be a platform for the next generation of practical safe and effective immunotherapies.
Do you find the assets at Advaxis more compelling than the products you explored while you were the Director of Medical Strategy for New Oncology Strategy at Bristol Myers ?
Petit: Again, I believe that Advaxis' immunotherapies could be a disruptive innovation in immunotherapies.
In order to have an effective immunotherapy, four essential elements are needed.
1. Access to Antigen Presenting Cells (APCs) -cells that direct the immune response to the right target. Unlike autologous immunotherapies, our immunotherapies do not require that you remove the dendritic cells and process them in a laboratory and make each person's cells their own treatment. Our immunotherapy vector meets the dendritic cells where they are, inside the patient and therefore one treatment can be used for every patient.
2. A strong cytotoxic T-cell response against tumor antigens is required. Advaxis immunotherapies generate a strong T-cell response to clear Listeria that is redirected to the tumor via the secreted antigens.
3. The ability to over-ride something called "Checkpoint Inhibitors" and "negative regulators" of cellular immunity is required. These checkpoint inhibitors are something utilized by cancerous masses to neutralize the immune response. Acute "perceived" listeriosis stimulates a maximum immune response that over-rides the checkpoint inhibitors.
4. The ability to over-ride Treg and MDSCs within tumor microenvironment, enabling killer T cells to kill tumor cells is required. Advaxis immunotherapies generate specific T-cells that access the protected tumor microenvironment and suppress immune protective cells within the tumor.
Other immunotherapies are trying to accomplish these elements through targeting specific aspects of this chain of components, however, to our knowledge, Advaxis' platform technology is the only immunotherapy that integrates all of these element into a comprehensive, single, well-tolerated, easy to manufacture and administer immunotherapy.
Personally, I have intentionally alternated between larger and smaller companies throughout my career. Both can gain from the culture of the other. Small companies can benefit from the organization, quality of research, and the commercial focus of the larger companies. But the larger companies struggle with implementing true innovation and are adverse to level of risks that one sometimes must take to bring forward a true paradigm-shifting innovation I believe the Advaxis immunotherapy represents.
Given your broad history exploring and examining immunotherapies, what gives you confidence regarding the platform's commercial success?
Petit: For immunotherapy to be truly successful medically and commercially, it needs not only to be proven safe and effective, but on the commercial side of the equation, it also needs to be practical, have a relatively low cost of goods so that patients can afford it and companies can still recoup their investment. It should also be versatile enough to be adapted to different stages of disease and fit in to the armamentarium of existing therapies in a logical way. This platform has the potential to be all of these things. For example, we don't have to remove the dendritic cells and process them in a laboratory and make each person's cells their own treatment, our vector meets the dendritic cells where they are, inside the patient and therefore one treatment can be used for every patient. Since the treatment is a live attenuated bacteria, it actually reproduces itself in culture, making the manufacturing process straightforward and cost effective. And since it alters immunologic tolerance in the tumors but does do so in the entire patient, we have no known toxicity problems from autoimmune symptoms that can be a problem with immunotherapies like the systemic checkpoint inhibitors.
So there's a tremendous market opportunity available in HPV, particularly overseas, which is where the company conducted the Phase 2 study for HPV in cervical cancer. You just presented the 18 month survival data at the premier conference for immunotherapy- SITC (Society for Immunotherapy of Cancer) just a few weeks ago, and I thought the data was pretty interesting, particularly relative to the current standard of care, Could you break down the data for the readers out there?
Petit: Patients with Recurrent/refractory cervical cancer like we treated have a difficult path ahead of them. The only real treatment option they currently have is chemotherapy. Most of these women will die from their cancer within a year or less. In the US, the most active treatment is combination chemotherapy that's difficult for patients to tolerate and sometimes associated with fatal side effects. The response rate is low and most responses that occur are short lived. The percentage of patients alive at 18 months with the best single agent chemotherapy was reported at 12% and even the survival rate associated with the most active combination chemotherapy identified to date was reported at about 20%. So considering the situation these patients are facing, the potentially availability of an immunotherapy like ours with minimal side effects that provides an 18 month survival in the range of 28% is an improvement.
I looked into the dosing regimen and the safety profile for ADXS-HPV, are you and the company planning to exploring how much dosing can be increase in order to power greater efficacy?
Petit: Yes we are. The results achieved so far have been with our lowest effective dose and with only 1 cycle of therapy. Our Lab data suggests to us that higher doses could still be well tolerated and should be more effective, and repeating the cycles of treatment, like we always do with chemotherapy, may significantly improve the survival of patients in our future studies.
And how does the data compare to the current treatments available to the same patient population? Does ADXS-HPV have a chance at first-line treatment for HPV-caused cervical Cancer?
Petit: We definitely think ADXS-HPV has a potential role in first line treatment and we plan to explore that potential in 2014. However the current standard of surgery followed by radiation and chemotherapy does a decent job for many patients. If ADXS-HPV is active in first line, it might result in fewer long term side effects than radiation and chemotherapy.
Given the extremely mild side-effect profile of ADXS-HPV, does this open the door for multiple combination therapies down the line for cancer therapy, possibly stepping into the same forefront as radiation and surgical excision?
Petit: We believe it does. In fact, we plan to conduct some studies to evaluate ADXS-HPV up front, before the standard treatment. If the patient's immune system can eliminate the cancer before chemotherapy and radiation has been given it would be better because the consequences of the conventional treatment could be avoided.
So how does Advaxis fit into the immunotherapy matrix? What are the differences between its platform as compared to the platforms that Immunocellular (NYSEMKT:IMUC), Northwest Bio (NASDAQ:NWBO), or Dendreon (NASDAQ:DNDN) are exploring and currently utilizing?
Petit: Well, All of these therapies start with a patient's own white blood cells (dendritic cells). These cells are collected, usually by leukapheresis, manipulated in the laboratory to activate and target them, cultivated and produced into a cell "product" that is given back to the same patient. The leukapheresis only accesses antigen presenting cells that are circulating. This process is complicated, labor intensive, and unfortunately quite costly. We don't have these problems, because our vector seeks out the antigen presenting cells within the patient where they live, including those that may not be circulating. The dendritic cells are activated and targeted in place by our vector. This is much simpler, more direct, significantly less costly and one ADXS-HPV preparation could potentially be used for all patients.
Given that Advaxis doesn't utilize an autologous platform for immunotherapy, what does this result in regarding research and cost to produce the drug?
Petit: The platform is quite versatile. The vector gains access to the APC and delivers whatever target fusion peptide we put in it. Like a Trojan Horse - which is the meaning behind the Advaxis Logo - it gets taken in to the "fort" of the Immune system. Once inside, it secretes the target fusion protein, like the soldiers pouring out of the Trojan Horse behind the walls. We can change the target by simply swapping out the plasmids that code for the target peptide. Once the genetic engineering is done, the loaded vector is self-replicating which keeps our cost of manufacturing relatively low. We don't need external GMP manufacturing labs to manufacture an autologous cell "product" like the dendritic cell. The immune system does it all from inside the patient.
How quickly can the company explore and expand into new oncogene-linked cancers?
Petit: Depending on the amount of animal modeling required, with a cooperative peptide we can go from concept to a laboratory scale new product candidate in about 3-4 months. We can even work in dual targets for a bivalent construct. We have built over a dozen so far targeting things like oncogenes, structural proteins, and receptors, tumor stroma and universal tumor antigens.
If the data for ADXS-HPV continues to perform at the same level displayed in the phase 2 trial, given your experience in bringing immunotherapies to market, is there a possibility that the company will have an accelerated process to an NDA for the indication?
Petit: Of course the decision for accelerated approval always rests with the FDA. We will do our best to come forward with the optimal dose and schedule and a robust study design, after consulting with the FDA. We hope that by showing good clinical benefit in such a serious unmet medical need, the treatment will be made available to the patients who need it as soon as possible.
Given the FDA's involvement with the entire drug approval process, how much FDA input has the company received thus far?
Petit: The FDA has been involved with us since before the first clinical trial as appropriate. We are looking forward to our next interaction with them which should be an "End Of Phase" 2 meeting to discuss our data and our plans for FDA registration.
Given the company's novel mechanism of action within the immunotherapy arena, do you believe that the assets would appeal to a large pharma company? For example, would Advaxis be a company on Bristol-Myers radar?
Petit: If Advaxis' immunotherapy is not on the radar screen of large pharma companies, perhaps it should be. BMS and several other companies are very much engaged in the immunotherapy space. Those oncology companies that are not currently engaged in the immune-oncology space are actively seeking ways to do so. The Advaxis approach is unique, innovative, and unlike any other. We think that it should be seen by a big pharma as an opportunity. As I said, the Advaxis immunotherapy approach is practical, appears to be well tolerated thus far, and we hope the future data we generate will further demonstrate that our immunotherapy technology is safe and effective. This platform has tremendous potential in our opinion.
With your history in medical strategy at large pharma, given the current landscape in cancer treatment, what are the chances that reimbursement policies will favor the commercial success of the company's listeria-based vaccines?
Petit: Reimbursement will clearly follow wherever a real and meaningful clinical benefit with an acceptable risk/side effects can be demonstrated. The promise of immunotherapy is to be able to provide the maximum clinical benefit with the minimum possible toxic consequence. I came to Advaxis because I think we have the best chance I have seen so far at delivering on the promise of immunotherapy.
You're also examining other potential oncogene-linked cancers. Could you discuss what other interesting candidates that are in the works?
Petit: Beyond ADXS-HPV, we are most excited about now about our ADXS-PSA prostate cancer construct and our cHER2 immunotherapy. Our PSA works great in models and prostate cancer is a disease where another immunotherapy has been shown to improve survival. Also coming up is our cHER2 immunotherapy. This treatment is also being tested in the veterinary world where it has been showing an improvement in survival when used to treat a bone cancer that occurs in pet dogs (not dogs breed for research purposes) that is also caused by HER2.
So you have ADXS-HPV for cervical, head and neck, and anal, ADXS-PSA for prostate, and ADXS-HER2NEU+ for breast cancer. How does this all fit together? Going forward, how do you believe investors should think about Advaxis in regards to its therapeutic focus?
Petit: This all fits together to make Advaxis an exciting and innovative biotech company with an enormous potential. If I look down the road, subject to regulatory approval of course, I can see us marketing ADXS-HPV for cervical cancer, HPV+ Head and Neck cancer and anal cancer. We could also be potentially looking at approvals in prostate cancer and HER-2+ breast cancer. Add to that the fact that Advaxis has worldwide exclusive license, with the right to grant sublicenses to its technology and a versatile and exclusive platform, and I can only imagine the value of that future company. I know that our CEO Dan has said that his vision is to make Advaxis the leading immune-oncology company in the U.S.
Fantastic, so we've seen the data from the 18-month survival data presented at SITC. What would you say the next big data readout investors should looking forward to with Advaxis?
Petit: Investors should be looking next for executional milestones such as the initiation of exciting new studies with nationally recognized centers of excellence that will begin to read out in 2014 and lay the foundation for additional indications and generation of the data needed to seek regulatory approvals.
And is execution still on track to where you initially set it?
Petit: Our execution is on track. Operationally, we are enhancing our staff to include manufacturing expertise and additional clinical development staff. We're pretty focused on executing on our clinical development plans to build value for our shareholders.
Great. Dr. Petit, thank you for your time.
Disclosure: I have no positions in any stocks mentioned, but may initiate a long position in ADXS over the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.