Iovance Biotherapeutics, Inc. (IOVA) Earnings Call Transcript & Summary

Thank you for taking the time to join us at the B. Riley Oncology Investor Conference. My name is Justin Walsh, and I'm a biotech analyst, a new addition to the B. Riley team. For this session, we're sitting down for a fireside chat with Iovance Biotherapeutics. As we talk, feel free to submit any questions on the platform. While we might not get to every question, we'll do our best to answer as many as the time allows.

So to jump right in and to start off, can you introduce yourself and provide a brief overview of the Iovance story?

Absolutely. Hi. Good morning. Thank you for the invitation. My name is Maria Fardis. I'm President and CEO here at Iovance Biotherapeutics. We are a company developing cell therapy for solid tumors, and we are in late-stage development for such cell therapies in terms of development and conduct of pivotal programs in melanoma and cervical cancers.

All right. So can we start off with a high-level description of what TILs are and maybe a brief history of the development trajectory from bench to the cusp of commercialization?

Yes, of course. So tumor-infiltrating lymphocytes are a patient's own immune cells that come to the site of tumor when a tumor is detected or cells that are unhealthy detected in the body. In a healthy individual, when cancer cells are detected, the immune cells that are called tumor-infiltrating lymphocytes come to the site of tumor and they launch an attack. In the cases where the individual is healthy, those cells are removed. In the cases where there's either environmental factors or genetic factors that are underlying, sort of allowing the disease to prevail, the TIL still comes to the site of tumor, however, due to the strength of microenvironment or other factors, the TIL is not able to completely clear the tumor. They're not able to do their job. That recognition component, however, is still there. Combining this with the history of the product, back in 1988, Dr. Steve Rosenberg at the National Cancer Institute, NCI, really recognized the component of immune system in addressing some of the solid tumors, specifically melanoma. And what he recognized is if he takes a piece of tumor and cut this into fragments, take the TIL out of tumor, expand them outside of the human body and putting them back into the patients, there's an opportunity for these TILs to address the tumor, specifically metastatic melanoma. In 2011, Iovance took a license of this technology from Steve Rosenberg. Back in around 2015, '16, we really started a more expanded development program where we initially requested an orphan drug designation for melanoma from FDA, and we received that. We then proceeded to change the manufacturing process that we had taken a license from, from Steve Rosenberg, into a more commercial-ready manufacturing process and the new product that we are using, called the Gen 2 22-day manufacturing process. We rolled this into clinic around 2017. We recognize that it continues to be a very potent product. In 2018, we continued enrolling into a cohort, called Cohort 2, in our melanoma program. We have released a lot of data from this Cohort 2, including long-term follow-up. And in 2019, we started our pivotal program for metastatic melanoma. In 2020, we completed enrollment into the pivotal Cohort 4. And we actually are in discussions with FDA in getting ready for submission of our metastatic melanoma BLA submission at some point in 2021 time frame. The second -- sorry about that, the second indication that we are also pursuing is cervical cancer. I'll spare you the details, but we are also in a pivotal program and in fact, completed enrollment in our Cohort 1 in cervical. So at a glance, this is a technology, and at a glance, this is where we are in terms of our development milestones.

So now that you've spared us the details, I'm going to ask you for the details. So what are some of the maybe key data points for both melanoma and cervical cancer that will really help support the potential approval?

Absolutely, and thank you for asking. So we are targeting a very treatment-experienced patient population. So that really makes a difference in terms of how we look at what is available care for those patients. It's important to recognize that the patients who have progressed on anti-PD-1, which is the standard of care in frontline, and then if they had a BRAF mutation, they have progressed on BRAF/MEK, really are considered unmet need. Their only available therapy would be chemotherapy, which would offer them somewhere around 10 -- maybe up to 10%, it's typically 4% to 10%, as the report in terms of response and an overall survival of around 7 to 8 months. So it's a highly unmet medical need despite the fact that great agents have been developed in metastatic melanoma. So in this [ part of ] the patient population, we conducted a study, we call that the Cohort 2 in our melanoma program, with 66 patients that were dosed. Mean number of prior therapies was 3.3. So they had -- 100% of these patients had received prior anti-PD-1, and 80% had received prior anti-CTLA-4. If they had a BRAF mutation, they would have received BRAF/MEK. We were delighted to see around a 36% response rate by investigator. We have now reported this data by Independent Review Committee or IRC. And then we see around a 35% response rate by IRC. So there's a really nice concordance in this specific cohorts data readout. And what was new is early part of this year, we did a follow-on data cut, given that we had not reached a median duration of response with a very long study follow-up and we still have not reached a median duration of response. So the current data cut allows for 28 months of median study follow-up, and we still haven't reached a median duration of response. This is really highly encouraging for a onetime treatment for this particular patient population. Going to cervical cancer data, we had released data some time ago, it was at ASCO about a couple of years ago. Once we agree with FDA that a program is registrational, we don't typically read it. So this is the last set of data we have from our cervical cancer patient population. We had 27 patients that we had read. Mean number of prior therapies was 2.4. Standard of care in frontline has been what's called the GOG-240, which is chemotherapy basically. So 100% of patients had received platinum-based therapies as well as many of them had received taxanes and anti-VEGF. In this fairly heavily pretreated patient population, we saw a 44% response rate in 27 patients. A median duration of response had not been reached at 7.4 months of median study follow-up. So this was highly encouraging. This is why we expanded this program after discussion of the indication with FDA. We completed enrollment into our Cohort 1 of cervical cancer, which was directly supportive of the pivotal indication. In the meantime, we are also considering potentially using Cohort 2 as potentially supportive of a cervical indication, that Cohort 2 allows for enrollment of patients who have received prior anti-PD-1. And we think this could be very encouraging because we believe the landscape of care may be changing. We are aware that early line may become a chemo-immunotherapy combination. So the end points that we have used are ORR and DOR, and our pivotal program has been based on a lot of data that we have released on Cohort 2 in melanoma and Cohort 1 in cervical cancer. And those are sort of the data that we have disclosed to date in support of potential registration.

Got it. So what else has the FDA requested to support the BLL -- BLA filing? And how is Iovance addressing their questions?

Absolutely. So not fully typical cell therapies, CMC matters and how we release our product is of high interest to the agency. In general, we release our product under a matrix of various assays that include identity, viability, total viable counts, [ certainty ] and potency. Potency has been the subject of discussion with the agency for some time as a matter of fact. And we continue providing information to FDA. Our standard release assay has been a cytokine assay, which is our preferred method. It is a gold standard assay for TIL. A lot of our advisers and KOLs have also been recommending that this would be the release assay. As part of the Type B meeting that we held with FDA around early October of 2020, we had discussion around clinical data and we agreed on the amount of follow-up. But at the same time, we discussed the potency assay. And the agency had additional questions, and we continue providing responses to them. As a result of that exchange, what Iovance is doing is on the cytokine frontrunner assay, they had -- FDA had requested additional information. We have provided that information to FDA since then. Under a second set of assays, the information of this assay was also provided to FDA previously. But we committed to validate the assay and provide that information to the agency. And this is work that is ongoing. We anticipate to provide this information to FDA in the next few weeks to months. And the third bucket of assays that we had considered is a number of different research assays that we had developed at Iovance, and we continue progressing them and preparing them for what's called a commercial release assay and possibly having them ready in case the agency wants to hear about that. So we continue to dialogue with FDA, and we are planning on reaching agreement in 2021 and submitting our BLA for the melanoma program in 2021 as well.

Got it. That's very, very interesting. What -- sort of while you're working on that and figuring that out, what are the pre-commercialization activities that Iovance has been -- has currently underway?

Absolutely. Given the exchange with FDA in early October time frame, we have taken a very gated approach to commercial readiness in terms of expense and headcount. We want to make sure we have visibility to the submission time frame before we expand our commercial team any further. But we do have an excellent and very strong commercial team in place. In general, more than 76% of Iovance's organization has well over 1 year of cell therapy or significantly larger. So this is a very, very solid team with extensive cell therapy experience previously. The areas where we have focused on with the group that we have on the ground is really we are building a lot of partnerships with U.S. cancer centers and building their TIL service line. In fact, we continue working with them in terms of engagement. We're receiving very positive feedback in terms of interest in commercializing the TIL immunotherapy. We continue preparing these sites for commercialization. A second approach has been our market access team continues to meet with private payers as well as the Centers for Medicare and Medicaid Services or CMS to assure that there is patient access. Aspects for lifileucel has been discussed and agreed upon. And we understand that CMS and the payers recognize the unmet need, and they are interested in assuring that there's appropriate access when the product becomes commercially available.

Got it...

We continue -- yes, go ahead. We continue...

Yes...

No, no, just we continue to sort of preparing the market on many fronts as well as internally to assure that we have a smooth commercialization when we are ready.

Perfect. Yes. That makes total sense. The advocated approach totally makes sense. You sort of touched on this a little bit, the -- that your current products are like the Generation 2 manufacturing process. And I believe you have at least a Generation 3 and maybe a couple of other processes in the works. So can you describe some of the differences between the manufacturing processes that Iovance utilizes and maybe some of the vein-to-vein times associated with those?

Absolutely. And sort of you're correct. We have -- let me break it down to maybe 5 groups. We had Gen 1, Gen 2, Gen 3, and these are sort of the mainstream processes that we have been developing, and 2 other products that are slightly different. One is PD-1-selected product, and one is called a -- peripheral blood lymphocytes or PBLs. Thinking about this, let's just talk and maybe focus on Gen 1, Gen 2, Gen 3. Gen 1 is -- will be licensed from NCI, was a process that takes about 6 to 7 weeks in manufacturing duration. And we optimized the process. Nonetheless, we felt that 6 to 7 weeks is a very long time for today's patient population. We prefer not to have to have the patient wait for so long. So in this process, we shortened the manufacturing process to a 22-day manufacturing. And the goal was to keep the profile of the product very much the same to the DP we can with Gen 1. We found out that our Gen 2 has some better youth markers, which is not surprising. This has been reported before by Steve Rosenberg and others. When the duration of manufacturing is shorter, youth markers for the cells are more favorable. So Gen 2 is the one that we have extensively rolled out into clinic and we intend to commercialize. At the same time, we have changed our goal a little bit, that what is possibly the shortest method that we can produce the same number of TILs with very similar profile than Gen 2, and we know we can shorten that and that became our Gen 3 manufacturing. So that's a 16-day process. And in fact, we are rolling that into clinic as well to better understand the product.

Got it. That's all very interesting. And that sort of leads into my next question, which is beyond melanoma and cervical cancer, where do you feel TILs have the greatest opportunity to impact the solid tumor treatment landscape? And I know that some of your more advanced or programs that you've emphasized are head and neck cancer and non-small cell lung cancer. What data has you excited for those indications or thinking that TILs might be the right approach for those?

Absolutely. So in general, [ Dr. Rosenberg has known ] that TIL can be very productive, helpful in treatment of very broad classes of diseases he calls epithelial cancers. So there was a very small amount of data on head and neck, and so we started thinking head and neck could be an indication we could pursue. And head and neck has been one of our top priority indications. And over the course of a few years, we partnered with academic institutions for various new indications. And in fact, one of our partnerships has been with Moffitt Cancer Center in administering TIL for non-small cell lung cancer. So we looked at both of these indications. The head and neck indication certainly has been of interest. It's quite an unmet medical need. Why do we look at other indications? We also think about could we consider a combination of TIL plus available care in earlier line of therapy. So for head and neck, some of our recent data shows that combining TIL plus KEYTRUDA in earlier-line patients, in fact, yielded a 44% response in patients that were mostly chemo-treated already as their frontline therapy. So this is very exciting for us. So as other indications, we obviously are pursuing head and neck and we are expanding our cohort that allows for TIL plus KEYTRUDA to be administered. The other indication you mentioned is non-small cell, and we are very interested in non-small cell. Having seen data from Moffitt, we actually have made a meaningful effort in expanding a program in non-small cell. We have 2 sets of studies where we are evaluating non-small cell lung cancer. One is registration-directed. It's for second-line patients. And the other study, the basket study, allows for 3 cohorts of non-small cell patients to be enrolled. And again, I won't go into details, but it is interesting to look at early line in combination with available therapies, such as KEYTRUDA or ipi/nivo or second line as a single-agent TIL or very relapsed/refractory patient population. That's how we are thinking about sort of positioning TIL, and we have programs to address all of those patients.

That's sort of, again, that addresses what I was going to ask next, which is how do you decide one potential combination partner over another? Like you mentioned ipi/nivo, pembro. What's the rationale for picking one over another in this indication or that indication?

Yes, very good. We do look at what is available care and well-adopted for that particular setting. So for example, when we started our cervical program, KEYTRUDA was not approved as a matter of fact, so we started as single -- a sort of single treatment for TIL in relapsed/refractory patients in second-line metastatic. As KEYTRUDA became an available care, we recognize that these products are obviously, [ they were ] well-adopted. So a combination with KEYTRUDA and the appropriate patient population is of interest. So we do react to sort of what is the landscape for those indications. In non-small cell, for example, we have noted that, of course, KEYTRUDA has taken a very strong position in early line of treatment for non-small cell patients. So we have a KEYTRUDA combination program. But at the same time, ipilimumab combination with nivolumab has taken a position, and it is a chemo-sparing regimen. So it's been an interesting cohort to maybe consider TIL plus ipi plus nivo both because it is now on NCCN guideline, ipi/nivo combination is, as well as the fact that this may be a chemo-sparing regimen. So we think that TIL can be sort of a platform that can be combined with available cares in different settings. And we pay attention to the changing landscape, trying to adapt to what is coming in terms of those specific disease settings. That's how we think about combinations.

This could be a -- I don't know how much of this you can answer, but this might be a bit of a timely question. With the Biden administration coming in and the potential for maybe more than lip service for pricing questions coming to the fore, what is your thinking with respect to the market being able to handle the cost of a TIL combined with checkpoint inhibitors, which are quite expensive in and of themselves? Do you think that you can make a strong enough case for the value proposition? Or what is -- what's sort of your general thinking on that front?

Yes. Excellent question, actually. So first and foremost, we simply haven't priced TIL itself. So we don't quite -- we haven't given guidance. But I recognize that what you're asking is the comparator agents are not exactly cheap. I do want to highlight a couple of factors. I think that really, ultimately, at the end of the day, as drug developers, data rules. If we have really outstanding data that offers a solution for patients, there really -- the payers ultimately have the same goal: to make sure that their patients receive the appropriate treatment; and they're able to -- really the best solution is to not have that patient become relapsed/refractory and out of options. Those are more and more expensive settings. So the best solution for patients is if we are able to address the patient early with a onetime treatment, there certainly is value in making sure that we offer these therapies to patients. So as we think about sort of how to position a product, I think, from my perspective, first and foremost, clinical data matters. Let's take a look at the data and see what it is that these patients can receive as an alternative therapy. And maybe I'll highlight a couple of things. In a disease which is non-small cell, we still see a significant death rate unfortunately. By second line, many of the patients in non-small cell lung cancer -- actually, not just non-small cell, many of them don't make it to second line. More than 50% of lung cancer patients, before they reach the second line, they have passed away. So this is still despite the fact that we have developed really excellent therapies for, in general, lung cancer. There remains to be an unmet need, where more than 60% of the patients shouldn't be dying before they reach the second line. So from my perspective, I understand the point you're making, and I do think that it's important that we pay attention to clinical benefit first. If we do have clinical benefit, then we can think about how to position the product. If we don't have clinical benefit, I don't think we have to worry about it. The second point that I think it is important is in cancer, we really are not seeing curative therapies. It's very difficult to see long-term curative therapies. So combination is the name of the game. That's just how it is. We have to make sure we offer the patients everything we can give them and not have them relapse.

Got it. Yes. That makes total sense. And now we're going to switch gears a little bit and kind of go back to -- this is something that you touched on with the manufacturing. But looking at a couple of your assets, LN-145-S1 and IOV-2001, how do those specifically differ from your other TIL products?

Yes, you're right. They're different, and I didn't touch upon them earlier because they're a slightly different bucket. The Gen 1, 2, 3 really have been mainstream use [ for ] tumor and to shorten the manufacturing process. So they possibly fall under process optimization categories. These 2 are slightly different in terms of the product that they offer. The S1, LN-145-S1, is a subpopulation of TIL. So it's a PD-1-selected subpopulation of TIL. There has been literature that has referred to this as potentially being a more potent product in addressing solid tumors. We also presented some data at SITC, I think it was 2018, where we show that the potency of this product is expected to be higher at least in ex vivo assays. The IOV-2001 is an entirely different product. As a matter of fact, it is a cell therapy approach for hematology. We are using peripheral blood lymphocytes, which is from a patient's blood. We use about 50 milliliters of a patient's blood. And we are able to grow a highly polyclonal cell therapy product that is expected to address hematologic malignancies. This is also a 9-day manufacturing process, and we have started -- as a first indication, we have started administering this product in CLL patients. And that's a fairly new program for Iovance. So very different products compared to our solid tumor Gen 1, Gen 2, Gen 3 products.

Got it. So a couple of questions as we're heading towards the close here. How has Iovance navigated the pandemic? And how do you see 2021 going as we sort of have those dueling trends of vaccines becoming available, but also a rise in cases in a lot of areas of the world?

Yes, absolutely. So through 2020, we were able to, for the most part, we were able to manage most of our activities remote and continue to stay on time. I think one of our key areas of activities was our manufacturing facility called Iovance Cell Therapy Center or ICTC. We managed to stay on target in terms of activities of building the clean rooms and intend to start our clinical manufacturing in 2021. So we are very much on schedule with that. However, you're right. As we are seeing additional spikes in COVID in various states, particularly as it pertains to U.S., we are seeing impacts -- some impacts on patient enrollment, and we are seeing it in mostly in early-line cohorts, where patients have alternative therapies. They can receive them at their local institution, and they may not want to travel to an academic center to receive an exploratory therapy. We really cannot wait for a vaccine to get rolled out and for the disease to be better controlled because ultimately, it does impact everybody and as well as drug development process.

And I think we can all agree on that one, at least. So why don't we finish off here with what are the key catalysts and/or data presentations and events that we should look out for from Iovance into 2021 and even beyond that.

Absolutely. So our front-and-center focus remains interactions with FDA, as you noted earlier. We absolutely are motivated to assure that we provide the agency any information they can ask for and reach agreement on a path forward for a BLA submission for lifileucel. We continue working on all other fronts for our other indications in cervical cancer. We completed enrollment into Cohort 2. We haven't dosed our last patient, but [ we look ] forward to dosing our last [ patient ] in that program. As a note, to just remind ourselves, that may be a cohort that could be included into the BLA for that indication. In head and neck, we completed enrollment into our C-145-03 study. However, we expanded our cohort in TIL plus KEYTRUDA combination in early-line patients due to the encouraging data we have seen and presented at SITC of last year. And in non-small cell, we really have taken a number of steps to expand our footprint. In addition to a study called IOV-LUN-202, and I look forward to having patients dosed into that program, we have added a cohort into the basket study, so we have now, in total, around 5 cohorts that we are enrolling into the non-small cell lung cancer program. In melanoma, we are initiating a cohort that allows for Gen 3 product, a 16-day manufacturing product, to be administered in that patient population. And last but not least, as we noted, we talked about it, we are looking forward to having ICTC up and running, our manufacturing facility, ICTC up and running, to continue with clinical manufacturing of our products through the course of 2021. So that's sort of the high-level focus areas for us through the course of the year.

Got it. It's all very exciting. I want to thank you for taking the time to be with us today. The talk was very informative. And have a great day.

Thank you very much.

Bye.

Bye.