Cell therapies have been a big focus in the cancer immunotherapy world over the last few years. This is where instead of using a traditional drug, a patient’s own cells are used for the treatment. One type of cell therapy, called chimeric antigen receptor T-cell therapy (CAR-T), has already even been approved by the Food and Drug Administration to treat certain types of blood cancers. Other cell therapy approaches currently under development include T-cell receptor therapy (TCR) and tumor infiltrating lymphocyte (TIL) therapy. The Cancer Immunotherapy ETF (Nasdaq: CNCR) index fund has exposure to all of these technologies across multiple companies. View all holdings of the Cancer Immunotherapy ETF.
In early February, we attended the Immuno-Oncology 360 conference in New York and caught up with Maria Fardis, Ph.D., MBA, President and CEO of Iovance Biotherapeutics. Iovance is a leader in using the tumor infiltrating lymphocyte (TIL) approach to cell therapy. This is where a patient’s own cancer-targeting white blood cells are isolated from tumors and grown outside of the body to produce billions of cells before infusion back into the patient to treat the cancer. In our exclusive interview below, Dr. Fardis tells us more about how TIL therapy works, what types of cancer Iovance is currently targeting, and describes a new technology the company is also working on. Below is a transcript of our wide-ranging interview, which has been minimally edited for clarity.
CNCR ETF: Thank you for joining us. Maybe to start, can you please introduce yourself and tell us about your background in the biotech industry?
Maria Fardis: I am President and CEO at Iovance Biotherapeutics. I am a biotech veteran, with two decades in the biotech space in drug development. About the last ten years of my career has been in oncology. By training I am a chemist and received my Ph.D. at the University of California at Berkeley. I have been in the Bay Area for about 25 years. A couple of the companies I worked for earlier in my career were acquired so they are all part of larger companies now. I also spent about 10 years at Gilead Sciences.
I started working as a bench chemist and then during my course of time at Gilead, I started moving to the business side. The transition happened as I was doing an on-site MBA while at Gilead while exploring alternative career paths. I transitioned to a role in Project and Portfolio Management, started working on an early oncology program and got very excited about work in oncology. I decided that I really wanted to stay in the field.
Back then, around 2007 or 2008, Gilead did not have many oncology programs. After I had spent a few years in oncology, Gilead ended up divesting the program I was working on and I decided that I would really like to go to a company where the focus was oncology. I moved to a company called Pharmacyclics, where I worked on a drug that has now become Imbruvica. It is a product that is now approved and used for a number of blood cancers. It was a wonderful experience to be able to work on a product that is available for patients. Pharmacyclics was ultimately acquired by AbbVie for $21.5 billion. After about four years at Pharmacyclics, I moved to another company called Acerta Pharma. After a year of being at Acerta, it was sold to AstraZeneca for $4 billion upfront and up to $7 billion total value.
After Acerta, I was in a position to seriously consider “what is the next thing for oncology?” I felt that personalized therapies were very appealing. Cell therapies were being evaluated for the treatment of various cancers. It still was almost considered science fiction back in 2016, but I thought there was definitely value in pushing these programs forward. I will give credit to predecessors in the industry who brought two CAR-T programs into the market because now CAR-T is a mainstream treatment for some blood cancers. What we work on at Iovance is cell therapy for solid tumors, whereas CAR-T therapy is only approved for blood cancers. Blood cancers are a frontier effort at Iovance that extends upon our therapies for solid tumors.
CNCR ETF: Your technology is called TIL (tumor infiltrating lymphocyte) therapy. Can you describe what that is?
Maria Fardis: When a cancer is caught anywhere in the body, the immune system typically launches an attack. It brings various cells, including white blood cells – lymphocytes – to the site of the tumor. Typically our immune system can fight activity that might be considered cancerous. This is one reason cancer is less common among younger people. As we age, our immune system gets a little weaker. The pressure of environmental factors, such as ultraviolet radiation and factors that affect cell replication, contribute to a possibility of cancer developing. The immune system is still doing its job, but the activity of the T-cells that come to the site of the cancer might not be strong enough to fight the cancer.
Our technology involves removing those cells at the site of the cancer, expanding them to large numbers, and putting them back into the patient and allowing these billions of cells to try to do the job of a normal healthy immune system. The cells are the patient’s own cells and they are not genetically modified. It is typically a one-time treatment that is expected to have a long term response.
CNCR ETF: This technology originated at the National Cancer Institute in Washington, DC. Is that correct?
Maria Fardis: Yes. Dr. Steven Rosenberg, who has been the innovator of this idea as well as a lot of other cell therapies, initially started working on TILs in 1998. He optimized the process of TIL technology over decades. Iovance licensed the technology in 2011.
CNCR ETF: Growing billions of cells sounds complicated. Can you describe the process more? For example, how is the process from a patient perspective? And what do you do behind the scenes with the cells to grow them?
Maria Fardis: Although there is some complexity involved, TIL therapy can clearly be a commercial process. It took a number of years for our scientists to optimize the process to make sure it is something that can be done routinely. I’ll talk about the patient experience for clinical studies – commercial might possibly be a little bit simpler.
In a clinical study, the patient volunteers to participate and signs consent. Then they enter a screening period during which the physician makes sure the patient qualifies for the study. This takes up to 2-3 weeks on average. Then a resection is performed, where you open the skin – most of these patients are unfortunately highly metastatic so they have a lot of tumor in the body – and about a cubic centimeter of the tumor is removed. The tumor tissue is sent to our central facility for manufacturing.
The patient then recovers and leaves the hospital. They can come back as soon as about 3.5 weeks later to get their TIL cells by infusion. Before they get the cells, there is a seven-day course of chemotherapy to remove the hostile environment that might be present, helping allow immune cells to fight the tumor. The patient then receives their TIL cells, they receive concurrent treatment with interleukin-2 to assist the immune response, and about four days subsequent to receiving the TIL cells they are done and might be dismissed from the hospital in about a week. That is the entire regimen.
CNCR ETF: What kind of cancers are you testing this against in clinical trials now and what kind of responses and data have you seen so far?
Maria Fardis: We are testing it in metastatic melanoma, cervical cancer, head & neck cancer, and non-small cell lung cancer. The most mature data we have is in metastatic melanoma. We showed that in metastatic melanoma, in a very late line patient population who are very treatment experienced, we are seeing a 38% response rate. This is from 47 patients. We reported the data late last year. Of these patients, a number are still in response and they are being followed-up in the clinical study. Nothing actually happens to the patients subsequent to the one-time treatment so they are just coming back to the site to get checked up. They no longer are receiving any treatment.
CNCR ETF: In regards to the 38% response rate, what does that mean for the patient? Does that mean that their cancer has stopped growing or has reduced in size?
Maria Fardis: A response is defined as when a patient’s cancer has reduced in size by more than 30% in volume. We do have a number of patients in what is called “stable disease,” where the cancer was growing before they received treatment and after treatment the cancer is not growing anymore. There is a clinical benefit in that. For an official response, we only report for a patient whose tumor has shrunk more than 30%. If you include the stable disease patients, over 70% of the patients are either stable disease or have experienced a significant reduction of their tumor.
CNCR ETF: You talked with the Food and Drug Administration about those trials and the data you have seen late last year. You discussed with them what a potential path forward might be to do a pivotal trial and get this on the market. What did you learn when you talked with them?
Maria Fardis: The agency was very supportive. We were hoping to have a small study, one that is called single-arm. There are two types of studies that could be supportive of approval for the intended indication. One type is a randomized study, which is typically a larger study, and the other type is a single-arm study. If the patient population has a substantial unmet medical need, FDA may agree to a single arm study leading to registration. In this case, they agreed that the patient population has quite a significant unmet medical need and agreed that a single-arm study is sufficient for registration. As part of the interaction, we received what is called a “Fast Track Designation” as well as what is called “Regenerative Medicine Advanced Therapy” (RMAT). These are designations that FDA gives to products that are addressing an unmet medical need and the patient population is very late line.
CNCR ETF: Has that study begun? If so, when do you think it will have a final result? When would you hope to potentially have this on the market one day?
Maria Fardis: Yes, we just started reactivating the one arm in an ongoing study that is the registration component, called cohort four. We expect to finish enrollment of this cohort late this year or early next year. This might allow us to submit a request for approval from FDA by late 2020. If all goes well, the product could be on the market sometime in 2021.
CNCR ETF: Ok, so that is late stage melanoma. What are some of the other indications that you have trials ongoing or plans to start new trials?
Maria Fardis: The next indication we are focusing on is cervical cancer. Some of our preliminary data in cervical cancer has been released. We are seeing a 27% response rate in a small group of 15 patients. We are very encouraged by what we are seeing. These are also very late line patients and there are unfortunately very few alternatives available for them. These patients have quite a clear unmet medical need. We plan to start talking to FDA in 2019 to define what could be our registration path for this indication. That is likely the next indication we are going after.
CNCR ETF: Can you tell us what are the catalysts that investors and other interested parties should be looking out for in 2019?
Maria Fardis: In addition to our clinical program, we are looking to build out our own commercial facility. We did a round of financing in the September/October 2018 timeframe and we committed to our shareholders that we plan to start building our commercial facility. So breaking ground on our commercial facility is certainly a milestone we are looking forward to. In addition, we have a very full clinical pipeline and are expanding this pipeline. We are hoping to bring a new product into the clinic in 2019 for at least one additional indication.
CNCR ETF: Today we are at IO360, a conference about immunotherapy. A lot of the discussion here is about combining two different immunotherapies, or an immunotherapy and another type of drug together. Are you also thinking about using TIL therapy in combination with other medicines? Does TIL therapy lend itself well for that?
Maria Fardis: Yes, we do have trials that we are just initiating that combine TIL therapy with checkpoint inhibitors. We have some preliminary data from our collaborative partners and academic institutions suggesting that TIL therapy combines well with various checkpoint inhibitors. We are looking forward to starting trials in earlier line patient populations.
I do want to clarify that the studies we have now in metastatic melanoma and cervical cancer are for very late stage disease patients. The reason we are first conducting studies in late stage disease is to help obtain regulatory approval most efficiently, not because TIL therapy is limited to treatment for patients with late stage disease. It might be very beneficial for patients to start earlier with an immunotherapy instead of being so late-line. We are looking forward to having additional patient data in earlier line patients in combination with checkpoint inhibitors.
CNCR ETF: Are you working on any next-generation technologies?
Maria Fardis: Yes. We were just talking about our research program being very active and some of our activities are now making their way into the clinic. A specific one we can talk about is quite a different product than TIL therapy. It is called peripheral blood lymphocytes. This product is being generated from direct blood rather than the tumor and we plan to apply it in 2019 and take it in the clinic for blood cancers – specifically one called chronic lymphocytic leukemia (CLL).
CNCR ETF: Is there anything about Iovance that not all investors and other people are aware of that you wish were better known?
Maria Fardis: I think there are two aspects that we would like to emphasize in terms of the company and our technology. First, TIL is a platform. It is not just a single product. It is a platform under which we can develop a number of different products for different solid tumors. There are approximately 1.7 million new cases of cancer in the United States each year and approximately 1.6 million of those are solid tumors. This is where is the TIL technology shines - in the solid tumor space. That is a significant unmet medical need. Second, in addition to this being a platform technology, is manufacturing. It used to be very difficult to manufacture cell therapy technologies. That is no longer the case. We have optimized the process extensively and significantly and now have significant control over it. We have a central manufacturing facility both in the United States and two facilities in Europe. We are able to provide cryopreserved (frozen) product and we are able to wait for the patient whenever they want and are able to receive the product. I think those two points are very important.
CNCR ETF: The Cancer Immunotherapy ETF has been an Iovance shareholder for over three years. What does shareholder support mean to a company like yours?
Maria Fardis: No drug development company could survive without shareholder support. In 2018, we secured two rounds of financing. Our shareholders are incredibly supportive and we are so pleased to have the benefit of their generosity. $400 million was raised just during 2018. If it wasn’t for this type of funding coming into the company, there is no way that a therapy like cell therapy, as expensive and complex as it is, could be developed. Shareholder support is absolutely essential.
CNCR ETF: Thanks for all the important work you are doing for cancer patients. Best of luck on what sounds like a very busy 2019.
Opinions expressed are those of the author, interviewee, or Funds and are subject to change, are not intended to be a forecast of future events, a guarantee of future results, nor investment advice. Fund holdings and allocations are subject to change at any time and should not be considered a recommendation to buy or sell any security. AbbVie is not a holding of the Fund or affiliated with the Fund.