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

Good morning, and thank you for joining us today. My name is Malika, and I'm an associate in JPMorgan's Healthcare Group. [Operator Instructions] With that, I'm pleased to introduce you to Fred Vogt, Interim CEO and General Counsel; Jean-Marc Bellemin, CFO; and Madan Jagasia, SVP of Medical Affairs at Iovance Biotherapeutics. I know that they are all very excited to tell you about their story, so we'll turn it over to Fred and his team.

Thank you, Malika, and thank you to the JPMorgan conference and organizers for inviting us today. My name is Fred Vogt. I'm the interim CEO at Iovance, and it's my pleasure to present to you on the company and some of the great things we're doing in immuno-oncology. On Slide 2 of our presentation, you'll see our forward-looking statements. Just be aware of this. I'll be making forward-looking statements today in our presentation. On Slide 3, by the numbers, Iovance is the global leader in developing and innovating and delivering TIL cell therapy for patients with cancer. This slide shows some of the highlights of our -- the breadth and strength of our platform pipeline and assets. We've treated more than 500 patients with TIL therapy. We've got a 90-plus percent manufacturing success rate and our principal process that we use that we intend to commercialize to the 22-day proprietary manufacturing process. Our pipeline includes 6 active clinical trials, 4 solid tumor indications, 1 breakthrough designation and 1 RMAT, Regenerative Medicine Advanced Therapy, designation from the FDA and 3 fast-track designations from FDA. We had $661 million in cash as of September 30 of last year. We got more than 30 U.S. and international patents covering our proprietary technology, well above 325 employees now at the company and our employees have, on average, more than 4 years of cell therapy experience. Some of our partners and collaborators are also shown on the right-hand slide of Slide 3, including the NIH, who we continue to work closely with MD Anderson, Moffitt, Yale and Cellectis, and we have many other partners. On Slide 4 is a summary of our pipeline. We have a broad immuno-oncology pipeline that focuses on the top, on TIL monotherapy. Some of these studies, including Lifileucel in melanoma, we'll spend some more time in more than a few minutes. We've also got a broad portfolio of combinations of Lifileucel and LN-145, both of which are Jet2 TIL product. In combination with pembrolizumab, or with ipilimumab and nivolumab, in a range of indications, including melanoma, cervical, non-small cell lung and head and neck cancers. We've got a PD-1 selected TIL product, which is designed to be more reactive against neoantigens that are produced by the patient's cancer. That's what we call LN-145-S1. We've got 2 studies running there. We've got a third generation or Gen 3 TIL manufacturing process, which we have several studies running to evaluate the efficacy of that product. We've got something called peripheral blood lymphocyte or PBL therapy, also known as IOV-2001, which we're studying in CLL post-BTK inhibitor. And then, we've got 2 new assets in light blue at the bottom here, that are coming to the clinic very soon. IOV-4001, which is our PD-1 and activated TIL product, PD-1 knockout or genetic knockout. And then, we've also got our IL-2 Analog, IOV-3001. Moving to Slide 5. This slide tells you a little bit about TIL, as a platform, an autologous cell therapy platform, developed primarily for solid tumors, but now we've extended it in hematological malignancies as well. It has a unique and differentiated mechanism of action compared to other immuno-oncology agents out there, including checkpoints. It's highly personalized to onetime therapy. And it's essentially -- the patient's immune system is amplified or rejuvenated by the process that we use to grow TILs. What we do in the process is sketched out on the right-hand side of Slide 5. We basically remove a tumor from a patient. We expand and rejuvenate patient-specific T cells from the patient, TILs, and then we lift at the fleet and reinfuse those cells back to the patients. On Slide 6, the mechanism of action at TILs, is, like I said, very unique, very different from other immuno-oncology agents. What we do with TIL cell therapy is we use billions of personalized patient-specific T cells. We call them polyclonal because they have many different T cell receptors on them. We use these to recognize and target a multitude of nonoverlapping neoantigens to patients with solid tumors. So, each patient has their own unique neoantigen profile. There's very few shared antigens between patients. We use a bulk TIL product that can target thousands or hundred -- at least, hundreds of neoantigens, up to thousands. And we provide this response to patient. Now, the way this works is, TILs are in the circulation, they migrate to the tumor, they are infused in the circulation, they migrate to the tumor. They're attracted there by chemokines. In the tumor bed, they infiltrate into the tumor bed, and then they remain there, where they recognize tumor cells through a T cell receptor interaction with MHC Class I and Class II that depends on multiple neoantigen peptides. When the TIL sees a tumor cell that it recognizes, it kills it by releasing interferon gamma, granzyme B and perforin, which causes the lysing of the tumor cell. On Slide 7, we have our Gen 2 manufacturing process. This is our principal manufacturing process that we plan to use as our first commercial process. This slide sketches out the process that we use to manufacture TIL product using Gen 2. First, we have patient intake, then we have tumor sample procurement through a excisional biopsy. At step 2, step 2 then commences the manufacturing process with our Gen 2 process, takes 22 days. In the meantime, the patient can be lymphodepleted. We return TIL product to the patient and provide a single infusion single-dose product. We then follow with a series of IL-2 infusions over a course of less than 3 days and then the patient is discharged from their single course of therapy. It's a centralized, scalable and efficient GMP manufacturing process. On Slide 8, we show our Iovance Cell Therapy Center, what we call iCTC, which is in Philadelphia, Pennsylvania. It's a 136,000 square foot investment. It's LEED gold certified. It's the -- the first set of clean rooms are occupied right now and are producing products for clinical patients. We've got other clean rooms coming online. Clinical supply has been initiated. We expect commercial manufacturing to commence this facility upon BLA approval. And through the control of this facility, the very unique design of this facility, we anticipate a significant reduction in COGS, cost of goods sold. Slide 9 shows the significant market potential for solid tumors. Solid tumors represent a very large unmet medical need, 90% of all cancer cases, 1.6 million new cases in the United States alone each year. On the right-hand side, we showed the number of deaths and new cases each year for some of the principal cancers. At the top is melanoma, our principal indication that we're going at, with our first BLA. More than 7,000 deaths a year in the United States from this disease, which can be potentially addressed by a late-line therapy, such as Lifileucel or TIL product, post-PD-1 inhibitors. And then, we've also got 100,000-plus new cases, which could be potentially addressed by moving to an earlier line of therapy. For example, in combination with standard of care with pembrolizumab. Cervical cancer shows also serious numbers, lung, head and neck, breast, pancreatic and brain cancers. If you look at them all together, there's enormous potential unmet medical need as well as the potential to move to earlier lines of therapy. Moving to Slide 10. I'll summarize some of our clinical data now. Slide 11 shows our potential market for metastatic melanoma. Again, there's significant unmet medical need here, 7,000 deaths a year in the United States. In late-line melanoma, post checkpoint, there's an opportunity because it's second-line therapy right now with chemo, the overall response rate is only 4% to 10%, overall survival is only 7 to 8 months, very limited options for patients after they progress on checkpoint and BRAF/MEK inhibitors. Here's a quote from one of our principal investigators, Omid Hamid, from The Angeles Clinic, who talks about how important it is to have options, treatment options for patients who have failed checkpoint therapy. Slide 12 shows a summary of our data in post-PD-1 melanoma. We reported this at ASCO 2021. This is just in the past year, this is our most recent update on this. You can see from this slide, our overall response rate is 36%. We have not reached our median duration of response after 33 months of follow-up. There's a waterfall plot on the top right here on Slide 12 that shows the best overall response for the patients. You can see the very deep responses that we get. And then, if you look closely at this, you'll see some lines to drop down further that show the reduction in target lesions since the April 2020 data cutoff, so, patients continue to respond. This is a cutoff that occurred about a year after that. Patients continue to respond to their therapy with Lifileucel, even far out after the onetime dose. At the bottom right, we've got our swimmers plot, where we can see the duration of response. And you can see on the y-axis of this plot how long it's been since some of these patients receive their therapy and how durable the responses are. 17% of patients had a deepening of responses and 1 PR converted to CR after 24 months after receiving Lifileucel. On Slide 13 is a summary of the non-small cell lung market. Here, we've got a quote from Adam Schoenfield, one of our PIs again, who talks about how important it is to have different options, especially with cell therapies now, in non-small cell lung. It's the first experience for TIL monotherapy to show benefit of metastatic non-small cell lung cancer. Again, 132,000 deaths each year and available care is docetaxel with a 9% to 13% ORR in the second line non-small cell lung following progression on chemo and checkpoint. Slide 14 shows the response data that we highlighted at SITC 2021 just a few weeks ago for our lung program. This is what we call Cohort 3B of our COM-202 study, single-agent monotherapy TIL product. 21% overall response rate and we have 1 CR ongoing at 20.7 months. This is a heavily pretreated patient population. All patients received prior PD-1. 24 of all responders received chemo as well. 24 of 28 patients received greater than or equal 2 lines, prior lines of systemic therapy. You can see on the left-hand side, the waterfall plot at the top, showing the deep responses that we observe in these patients. And at the bottom, with the swimmers plot, on the left of that, it shows a number of prior lines of therapy and the best overall response to prior immune checkpoint inhibitors, ICIs there. You can see, these were critically old patients who had received many lines of prior therapy. They also run the gamut of PD-L1 expression, KRAS expression, and in the Moffitt study, which I'll mention here as well, a study we funded with Moffitt, we also had an [ EGFRx ] on 19 patient response. So, we see responses across the spectrum, highlighting the fact that TILs have a much different mechanism of action than checkpoint inhibitors. In the Moffitt study, which we funded, which is not shown on this slide, but it's a study that we funded, we saw 2 long CRs in patients that had been given TIL therapy immediately after progressing on nivolumab. This gives us some confidence that we can achieve long durations of responses in patients that are quickly moving from PD-1 therapy over to TIL therapy. Slide 15 summarizes -- shows a little bit about our TIL data in solid tumor settings in earlier lines of therapy. There's a tremendous unmet need to improve the rate and depth of responses with manageable long-term safety. Here's a quote from David O'Malley, who is one of our investigators who gave our presentation at SITC this year, our oral presentation on this data. This data set includes cervical cancer of melanoma and head and neck cancers and now in the early line, where standard of care, for example, in melanoma is 33% ORR with pembrolizumab or 17% ORR in head and neck. On Slide 16, we summarize the data for 42 patients given TIL therapy in combination with pembrolizumab in 3 different indications. Melanoma, cervical, and head and neck. If you look on the far left here, you can see the melanoma data. Cohort 1A is what we call this. In our COM-202 study, you can see multiple deep responses, every patient benefited. There's tumor burden reductions in nearly all efficacy-evaluable patients. And we've got deep CRs, or we're to going to the 3 green bars on the far right of the left most portion of this waterfall plot. 30% CR rate in these patients and a 60% OR rate that compares to a 33% response rate, as I mentioned on the earlier slide, with pembrolizumab alone and the CR with pembrolizumab alone is only 6%. Here, we appear to see 30% CR rate. With head and neck and cervical, we also have promising data. You can see, again, deep responses, CRs and -- all doing deep responses for many patients. On the next slide, Slide 17, we show the swimmers plot, showing that the durability of this therapy in the frontline is very, very good. We've got ongoing response to data cutoff in 4 to 6 patients in melanoma, 3 out of 6 patients in head and neck, and 5 out of 7 patients in cervical cancer. You can see on the left here, we have prior therapy types and PD-L1 status. So, we again see the gamut of different PD-L1 negative patients responding here. And the median study follow-up for each of these is 11.5, 7.8 and 7.6 months. Now, I'll turn to launch readiness. As we move towards our BLA, the company is focused on getting ready for launch of Lifileucel on melanoma and then in other indications. On Slide 19, we summarize some of the things we're doing with our manufacturing capability. First of all, we're trying to increase throughput up to thousands of patients a year, something that's never been done with TIL therapy previously, and that's something we're doing at our Philadelphia facility. I mentioned earlier, as well as with our network with CMOs. We're working on a redundant and reliable supply chain. We're aiming to reduce material costs, we're boosting our success rates and aiming for consistent success rates across our manufacturing, and we're trying to reduce overhead costs. On Slide 20, we show what we're doing -- on the commercial side. We're targeting a broad range of authorized treatment centers or ATCs across the country in the United States. This slide shows a map of the U.S. with some of the ATCs highlighted, in little small yellow circles. We're considering patient volume NCCN status, the presence of KOLs, existing cell therapy or bone marrow treatment centers in the presence of Iovance clinical trial experience when we pick these sites. We're aiming to launch with at least 40 ATCs, which will be a very broad launch for cell therapy. And we think that we can drive community referrals and prioritization by the fact that we know that most of the patients are concentrated in these centers. Slide 21 summarizes one of our most critical components of our launch, our a system called Iovance Cares. Iovance Cares is our integrated patient management system. It includes order submission, tumor procurement, order management, chain of identity, chain of custody and manufacturing in an integrated quality system tied to the patient's care. There's dedicated case managers in the system as part of the system, and then we've got integrated reimbursement and patient support capabilities. This is the customer-facing part of our product that faces patients and it faces caregivers, and we're aiming this to be the best in the industry at launch. Again, it's called Iovance Cares, and it's our patient support services and COC/COI system. It's also critical to the quality of our products, to some, the FDA looks at very closely when they approve your product. Now, I'll turn to our research pipeline on Slide 22. On Slide 23, this summarizes some of the things we're doing in research right now to generate the next -- to create the next generation of TIL products. First, we're trying to genetically modify TILs. We've got a long-standing collaboration with Cellectis to do TALEN gene editing to support clinical development of TILs that have been edited with TALENs. We're bringing our first IND for IOV-4001 to the clinic this year. This is a PD-1 or PD-CD-1 gene knockout product, and it will be the first multicenter trial of a TIL product like that. We're also developing more TIL products. We're working on the PD-1 selected TILs, and we're working on C39/69 double negative TILs. And you can see some of the references here on the slide, Slide 23, to the posters that we presented recently in some of these products. We're working to optimize the process with our Gen 3 16-day manufacturing process, which we're exploring in the clinic already within our COM-202 study. And we're working on core biopsies. Core biopsies have an advantage over excisional biopsies and that they can be done less invasively. In the LUN-202 study, we have a cohort where we're exploring core biopsy sampling in a 15 patient cohort for lung cancer patients. And this is something that could also change the paradigm of TIL therapy by making TIL therapy more of an outpatient procedure in the future. Finally, we're working on expanding TIL therapy in new regimens. With our IOV-3001 IL-2 analog that we licensed from Novartis, we're in the middle of IND-enabling studies this year. And that could enable us to remove the aldesleukin that we currently use in our products and replace it with something superior. Slide 24 digs in a little bit more to some of our new TIL products. We've got, not only the PD-1 and activated TIL product, which we call IOV-4001, which is expected to enter clinical study in 2022, but we've also got additional immune checkpoint targets from the Cellectis license from our own internal work. We've licensed technology from NIH on cytokine tether TILs and we're working on additional transient, stable gene insertion and activation products. These are all things that we hope to bring forward into our pipeline very soon, and we expect a lot of activity in '22 on these efforts. Moving to Slide 25, I'll give a quick summary of our financials and the company's milestones. First, on Slide 26, you can see we're well-capitalized in pursuit of commercialization of TIL therapy. We've got 156 million shares outstanding, and then we've got $661 million in cash as of September 30 of last year with an anticipated cash flow sufficient in 2023. On Slide 27, we summarize our 2021 accomplishments and our anticipated milestones for 2022. In 2021, we worked very hard to get feedback on our BLA, resolve some of the issues with our potency assays and prepare for a BLA submission in the first half of '22. We presented data on melanoma and cervical at SITC, at ASCO, we presented our first non-small cell lung data. We expanded our head and neck work, and we have been progressing our 16-day Gen 3 manufacturing process in the clinic. Finally, we completed our GMP facility in 2021, that was a major accomplishment, and began clinical manufacturing iCTC in 2021 as well. In 2022, our milestones include getting our BLA on file. We're on track for our first half of '22 BLA submission. We'll be talking more about Cohort 4 melanoma data in conjunction with that BLA submission. We've been enrolling and we continue to enroll our non-small cell lung study, which could be registration supporting or registrational depending on our FDA feedback that we're working on right now. We're also getting FDA feedback on our cervical strategy based on the changing landscape of care in cervical cancer, and we're working on progressing that into a BLA filing. We're continuing to define our strategy for TIL plus pembro combinations in early line. Some of these may become confirmatory studies for our late-line studies that we would bring forward for BLA accelerated approvals. We're very, very bullish about our genetically modified TIL products. We're going to initiate the first clinical study of 4001 and then, hopefully have some more assets coming forward there pretty soon. And our research pipeline is very, very active with us advancing new TIL products towards the clinic. In manufacturing, we continue to be ready for GMP commercial readiness, and we're going to work throughout '22 to prepare our facility for launch. Finally, Slide 28 provides a quick summary of the company with quick recap. We're pioneering a transformational approach to cancer therapy at Iovance using a differentiated immuno-oncology asset that works very, very well in many different indications. We've got a large market opportunity, a strong unmet medical need. Our initial focus is in the checkpoints, post checkpoint solid tumor indications. We're expanding into combinations in earlier lines of therapy, including the combination of pembrolizumab. And we've got companies functional trials in melanoma, head and neck, cervical, non-small cell lung, as well as CLL in our heme program. We have the potential to be the first cell therapy approved for solid tumor cancers. And we've got an accelerated path under the ARMAC designation with melanoma and we've got breakthrough in cervical. We expect the BLA submission in the first half of '22 for melanoma. And we've got Orphan, Fast Track and other designations for some of our other studies that we're running right now, so or other indications. We've got the efficient and scalable proprietary manufacturing under control here at Iovance. We've got U.S. and EU capacity with our CMOs. We've got the iCTC in Philadelphia that can serve Europe as well as the United States. We've got a rapid 22-day Gen 2 manufacturing process, the 90% success rate. We were the first in the industry to do something like this. And we've got the experience of treating more than 500 patients with our proprietary process. Finally, we've built the infrastructure for commercial success. We've fully integrated in experienced cell therapy team, a high concentration of patients at our ATCs. I showed you on the map earlier, we've got the Iovance Cares proprietary platform built and we're ready to go for launch. With that, again, I'd like to thank your organizers and thank you for your attention, and we'll turn to the questions.

Thank you, Fred. We have a couple of questions from the audience. For the audience members, please submit your questions using the blue ask-question button on your screen. To kick things off, we would love to hear a little more about the longer-term vision for the company.

Sure. I can start with that. The long-term vision for the company has essentially remain the leader in TIL therapy. We think TIL therapy is an important branch of immuno-oncology. Checkpoints, as you know, their mechanism of action includes the release of TILs to attack tumors. We're attacking it more directly using TIL therapy. We just have to solve the hurdle of using a cell therapy instead of something easier to administer like an antibody. The great advantage of TIL therapy is it's onetime therapy. It's highly efficacious and it's autologous and manufactured from the patients themselves, which is an advantage over allogeneic, other products where we have to worry about a lot of adverse reactions potentially. It's a very safe therapy. It's been developed for many, many years. And now, what we're trying to do, even longer-term vision, is engineering to TIL cells, even greater efficacy and potency. Starting with the PD-1 knockout and going beyond that to more advanced genetically edited TILs.

Thank you. The second question we have is, do you have any update for us regarding your search for a permanent CEO?

Right now, the Board is very active in a search for a CEO. They're interviewing candidates. We don't have any updates today. But if we get something, we'll put that out right away.

The third question, which I think you covered in your presentation, but it would be good to go over it again is, what is the status of your assay with the FDA?

Sure. Right now, the assay discussions are still ongoing with FDA. Our BLA is still on track to be filed in the first half. We don't see any slowdown as a result of this. We're in the midst of conversations with the FDA on our potency assays, including the new assay that we've developed as well as the broader sort of matrix of assays that one uses to get -- to measure potency for TIL products. And we think that should be resolved in time for us to progress on a normal BLA cycle and following the first half.

A follow-up to that was, could you share the feedback from the FDA on the results of this work, example the highlights from the meeting with FDA in autumn?

We haven't disclosed whether we had a meeting with FDA in the autumn or what's going on. We simply said we've had interactions with FDA, and we continue to have interactions with FDA. It's a very detailed process with a lot of steps, and we really don't want to be out there talking about each individual meeting. What I can tell you is the feedback has been positive. We think we have a path. They've given us very good advice. They've told us what they think they need to see in order to be comfortable with us being able to detect and release potent lots and screen out subpotent lots. So, we're pretty comfortable based on the advice they've given us, and they gave us a very detailed advice that we've got the right approach to solve this issue with FDA.

Thank you so much. I don't see any other further questions. We have enjoyed hearing about Iovance. Thank you for all the amazing work that you have been doing. Do you have any parting thoughts for us?

No. Thank you all for your attention. Yes, we very much agree that we're singularly focused on cancer patient care and trying to get these indications through to give patients a new option here, with a differentiated type of immuno-oncology agent. So, thank you for your support, and thank you for tuning in.