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

All right. Hello, everyone. Thanks so much for joining us on Day 2 of Oppenheimer's 32nd Annual Healthcare Conference. My name is Mark Breidenbach, and my research team covers emerging biotechnology for OpCo. The next presenting company is Iovance, which is developing a pipeline of tumor-infiltrating lymphocyte, or TIL, therapies for cancer, which we think are especially noteworthy because of their proven efficacy in solid tumors. Joining us for the discussion is the company's COO, Igor Bilinsky. We'll try and leave a few minutes at least at the end for Q&A. [Operator Instructions] So with that said, let's dive right into the presentation. Igor, I'm going to hand over the mic to you.

Thank you, Mark, and good afternoon, everyone. Great to be here today, and thanks for the opportunity to share Iovance's progress. We are a publicly listed company, and I'll be making forward-looking statements as part of this presentation. Please refer to our filings with the SEC for a full disclosure of risks and uncertainties associated with investing in Iovance. So Iovance, we are a leader in innovating, developing and delivering TIL therapies for patients with cancer. To date, we have provided TIL to more than 500 patients and have demonstrated more than a 90% manufacturing success rate. Our manufacturing process, Gen 2, that we've used in most of our clinical studies to date is 22 days. Our pipeline includes 6 active clinical trials in 4 solid tumor indications. And our programs include 1 Breakthrough, 1 RMAT, which is Regenerative Medicine Advanced Therapy designation and 3 Fast Track designations. We have a strong and committed team with about 350 employees who on average have more than 4 years of cell therapy experience. We ended the year 2021 with $602 million in cash. And we have a strong patent portfolio with more than 35 U.S. and international patents. Our partners and collaborators include some of the leading cancer centers as well as Cellectis who is our partner for TALEN, for the -- using TALENs to develop genetically modified TILs. This is an overview of our pipeline. The pipeline includes both monotherapy TIL clinical studies in melanoma, cervical, lung, and head and neck cancer. It includes combinations of TIL with checkpoint inhibitors such as pembrolizumab and ipi/nivo, also in melanoma, lung, cervical, and head and neck. It includes PD-1-selected TILs, next-generation, third-generation TIL manufacturing process, which is a 16-day process compared to the 22-day Gen 2. And it includes PBL therapy, which are peripheral blood lymphocytes that we're developing for hematological malignancies, and that's in the clinic for CLL. And then the next one is the PD-1 inactivated TIL, which we refer to as IOV-4001. You must have seen the news we released yesterday that that IND was allowed by the FDA and that we plan to initiate the first clinical study of this genetically modified PD-1 inactivated TIL in advanced melanoma and lung cancer this year. And we also have an IL-2 analog in the clinical development. As you all know, despite numerous approved treatments, there's significant unmet medical need that remains in solid tumors, and cell therapies have had very limited success in that area. About 90% of all cancer cases are solid tumors, which represent about 1.6 million new cases annually in the U.S. Our platform, tumor-infiltrating lymphocyte, TIL, we view it as a leading cell therapy platform for treatment of solid tumors. It has a unique mechanism of action and so TIL is highly personalized, and we're developing it as a onetime therapy. The -- to describe it in a nutshell, what it does, TILs are lymphocytes that are present at the tumor site. And when the cancer appears in the body, the TILs migrate to that area and control the tumor. When the tumor overtakes the immune system, the TIL is still present at that site. So what we do, we take those TILs, expand them, rejuvenate them and infuse them back to the patient, essentially amplifying and rejuvenating the patient's own immune system to provide therapy for their cancer. A bit more detail on the TIL mechanism of action. So TIL deploys billions of personalized patient-specific polyclonal T cells or TILs to recognize a target multiple of nonoverlapping neoantigens in patients with solid tumors. And what we've shown and others have shown is that these neoantigens are unique for each patient, and having this personalized therapy is important for developing an effective therapy. When TIL are infused, they go into circulation. They migrate to the tumor site. They recognize the tumor neoantigens presented by MHC class I and II and initiate tumor killing by lysis or other mechanisms. This slide outlines the patient journey through the treatment cycle. So the tumor sample is taken from the patient and is shipped to our GMP manufacturing facility where TIL is manufactured in the, in this case, Gen 2 20-day process. And the result of that is a cryopreserved TIL in infusion bags that is then shipped back to the treatment site. In the meantime, the patient undergoes non-myeloablative lymphodepletion to remove the hostile tumor microenvironment and then receives an infusion of TIL, followed by infusions of IL-2 that are intended to stimulate and promote replication of T cells in the patient. And then the patient is discharged. To build and maintain our leadership in this field, Iovance has built what we call Iovance Cell Therapy Center, iCTC, which is our in-house manufacturing facility. It is built-to-suit custom facility that's designed around our manufacturing process. About 130,000 (sic) [ 136,000 ] square feet and located in the Navy Yard area of Philadelphia. We completed commissioning of the facility last year and initiated the clinical supply from the facility for patients enrolled in our clinical trials in the third quarter of 2021. In parallel, we are preparing this facility for commercial manufacturing upon potential BLA approval. And importantly, having control of our internal manufacturing enables us to both further improve quality of TIL manufacturing as well as achieve potentially a significant reduction of COGS in the future. To build our leadership in the TIL area, we've also been very focused on the intellectual property portfolio. Today, we have more than 35 granted or allowed U.S. and international patents that cover compositions of matter for TIL products, methods of treatment in a range of cancers and various manufacturing processes. We also have a number of pending applications that cover selection of TIL, stable and transient genetic modifications, various manufacturing approaches, including cryopreservation. So now I'll move to providing some of the clinical data updates from our programs. Firstly, melanoma. Melanoma presents -- still presents a significant unmet medical need. About 300,000 new cases are diagnosed annually worldwide with about 60,000 deaths. And in the U.S., about 100,000 cases diagnosed every year with about 7,000 deaths. The first-line anti-PD-1 checkpoint immunotherapy provides responses reported in the 21% to 33% range as well as BRAF/MEK inhibitors are indicated for patients who are BRAF-positive. But once -- if patients fail the checkpoint therapy, second-line chemotherapy has very limited response rates in the mid- to high single digits and overall survival of only 7 to 8 months. These are the highlights of the melanoma data that we presented at ASCO last year. It's a single-agent lifileucel, our TIL therapy, that's provided to patients following their progression on anti-PD-1 checkpoint inhibitors. This cohort included 66 patients, and we reported a 36% overall response rate. And at the 33-month median follow-up, the median duration of response has not been reached yet. What is also encouraging is that many patients demonstrate responses that continue to deepen over time. In this case, 17% of patients had deepening of response. And in fact, one of them converted from a partial response to a complete response 24 months after lifileucel therapy. In the upper right panel, you see the waterfall plot, where responses in these patients are color-coded. In red, you see patients with progressive disease; gray, stable disease; blue, partial response; and green, complete response. And what you see is that most patients, about 50, had reduction in tumor size. And on the bottom, you see the swim lanes that show time to response for patients who achieved the partial response or better, and the arrows indicate patients who are remaining on study. And this, again, illustrates the durability of response in these patients. Moving on to non-small cell lung cancer. Large market with very significant unmet medical need, about 2 million new cases worldwide per year, with close to 2 million, 1.8 million deaths. And in the U.S., more than 200,000 cases annually with about 130,000 deaths every year. The first-line therapy for patients without specific driver mutations is generally checkpoint inhibitor plus chemo. And the second-line response to chemotherapy after failing chemo is very, very limited, only in the high single digits or low teens. These are some of the data we presented at SITC in November of last year. And these are data from the Cohort 3B and our IOV-COM-202 study that included patients who had progressed on anti-PD-1 therapy and were generally very heavily pretreated. So all of these patients had received either anti-PD-1 or anti-PD-L1. And vast majority of them, 24 out of 28, including all responders, had received 2 or more prior lines of systemic therapy. In the waterfall on the upper right, you see that most patients showed a reduction in tumor size from baseline and 21% achieved the response. And on the bottom right, you see the time to response for patients with partial response or better. And if you look at the top line in the chart, that's the patient who had achieved a complete response and actually remains in complete response more than 20 months later. And that patient had received 3 prior lines of therapy, progressed on the checkpoint inhibitor anti-PD-1 and had a PD-L1 TPS low score less than 1%. So the importance of this data set is twofold. On the one hand, we demonstrated that we can manufacture TIL for patients with lung cancer. And on the other hand, we show here that patients can have a response and a durable response to TIL therapy despite failing multiple other therapies for lung cancer, including the checkpoint inhibitor. So our initial strategy is to provide TIL for patients in late treatment -- late-line treatment settings post checkpoints. But we're now also investigating applications of TIL for solid tumors in earlier treatment settings, where there's still significant unmet medical need for achieving responses in more patients and responses that are deeper and more durable. And as a reference in frontline standard-of-care setting, pembrolizumab demonstrated about a 33% response rate in advanced melanoma with a 6% complete response. In head and neck cancer, the reported response rate for single-agent pembro is about 17%. And in cervical cancer, following chemotherapy, second-line pembro demonstrated response rates in the range of 11% to 14%. So these are the references of comparing this next data set that we also presented at SITC in November 2021 that shows best overall response for the combination of Iovance TIL with pembrolizumab in 3 different solid tumors: in melanoma, head and neck, and cervical cancer. What you can see from the waterfall charts, almost all patients exhibited a reduction in tumor size from baseline. And the overall response rate in melanoma was 60%, including 30% complete response rate. In head and neck cancer, the ORR was 39%. And in cervical cancer, the overall response rate was 57%. From the same data cut, this is the time to response for patients who achieved a partial response or better in the 3 solid tumors. And the median follow-up in melanoma was 11.5 months; in head and neck, 7.8; in cervical, 7.6 months. And what you see from this chart is that in melanoma, 4 out of 6 responders remained in response or 66.7%. In head and neck cancer, 3 out of 6 remained in response, which is 50%, including the top -- patient on the top who has been on study for now 27 months. And then in cervical cancer, 5 out of 7 patients remained in response, which is 71%. So we continue enrolling these cohorts and continue following these patients and look forward to presenting further updates when data mature further. Moving on to the next topic that is very high on our agenda is getting the organization ready for commercial launch. As you know, we want to file the melanoma BLA, submit the melanoma BLA in the first half of '22. And I'll just highlight a couple of aspects of launch preparation in manufacturing and in commercial. In manufacturing, Iovance, being the leader in this field, we are looking to build best-in-class manufacturing capabilities, both in-house and also through our contract manufacturing partners. This means increasing the capacity, increasing the throughput, building a supply chain that's reliable by including both redundant and reliable suppliers, reducing the cost, both the material costs and the overhead costs, and being very focused on maintaining and further improving the manufacturing success rates, which to date for us have been over 90%. On the commercial side, one major area of focus for us is selecting the right authorized treatment centers for launch. And a number of considerations are taken into account here, including patient volume, the location of the centers, their NCCN status and the locations of the major key opinion leaders in melanoma, the capabilities of these centers in cell therapy and bone marrow transplantation as well as, of course, locations of Iovance clinical trial sites. And then finally, last point I'll touch on today on the commercial preparation side is IovanceCares. It is our proprietary system that includes several aspects. One is chain of custody, chain of identity, COC/COI, which is crucially important for the field of autologous cell therapy. And there are also a number of customer-centric features that are designed for the academic -- the authorized treatment centers, including the patient management ecosystem and the quality program as well as patient-centric features, including reimbursement support, patient support, dedicated case managers. So we're putting all of this together in anticipation of launch to ensure quick ramp and good coverage for our lifileucel therapy. Research pipeline, I'll touch on this briefly. But what we are focused on, of course, is commercial, the BLA submission, commercial launch preparation, clinical programs. But we also intend to be the leader in this field. And we are investing in the next generations of TIL technology, which we believe can further improve responses for TIL therapy and provide responses for more patients and responses that are deeper and more durable. And there are 4 areas I'll highlight in our research efforts. One is the TALEN collaboration with Cellectis to develop genetically-modified TILs. And the frontrunner in that collaboration is IOV-4001, which is our PD-1 inactivated TIL for which we announced IND allowance by the FDA yesterday. And we plan to take it into the first clinical study in patients with advanced melanoma and lung cancer this year. The second area are various select TILs, where we're looking to modify the TIL phenotype in various ways, again with the objective of achieving responses that are deeper and more durable. And so one example of that is PD-1 selected TIL. Another example is CD39/CD69 double negative TILs, optimizing the memory-like phenotype of the product. We also continue innovating on the manufacturing process side. And one area I already mentioned is our Gen 3 manufacturing process, which is 16 days long compared to the Gen 2 which is 22 days, that's in the clinic. And we also -- we have demonstrated preclinically that we can manufacture TIL from core biopsy. And now this is an approach that's included in our LUN-202 clinical study. Finally, we have an IL-2 analog that we had in-licensed from Novartis, and that's in IND-enabling studies this year. And zooming in further on the genetically modified TIL area. In addition to the PD-1 inactivated TIL, for which we have an IND allowed now, we are exploring additional immune checkpoint targets. We're also exploring cytokine tethered TILs and also other transient and stable gene insertion and deletion approaches for TILs. And please stay tuned. We'll update you more on these programs once they further mature. Financials. We ended the year 2021 with $602 million in cash and investments, and that amount is sufficient, we expect, into 2024. So 2022, we expect to be a very important year for Iovance. Our key focus remains on submitting the BLA in the first half of 2021 for lifileucel in metastatic melanoma. We also expect to present various updates and make progress on our clinical pipeline, including sharing Cohort 4 data in melanoma. In non-small cell lung cancer, we are planning to execute on the strategy based on the FDA feedback and continue enrolling IOV-LUN-202 study, which is in second-line treatment setting. In cervical cancer, we are also planning to execute the strategy based on the FDA feedback regarding the path to the BLA for that indication. Combinations of TIL and checkpoint inhibitors and, in particular, pembrolizumab, in that area, we continue enrolling these cohorts and look to define early-line melanoma strategy. For genetically modified TILs, we plan to initiate the clinical study of PD-1 inactivated TIL, IOV-4001, this year in advanced melanoma and lung cancer. And research pipeline, we continue advancing our new TIL products toward the clinic. Finally, in manufacturing area, as I mentioned, we continue getting our in-house facility, iCTC, as well as our contract manufacturing partners for GMP commercial readiness. So to summarize, Iovance is a leader in innovating, developing and delivering to patients tumor-infiltrating lymphocyte and TIL therapies primarily for solid tumors. We are targeting a large market opportunity, with initial focus in both checkpoint solid tumors and then expansion into earlier lines of therapy. We're conducting clinical studies in melanoma, cervical, head and neck, and lung cancer as well as CLL. We believe we have the potential to -- for lifileucel to be the first onetime cell therapy approved for solid tumors and plan the BLA submission in the first half of 2022. The melanoma program has RMAT, Orphan and Fast Track designations. Cervical program has BTD, Orphan and Fast Track designations. We're building our efficient and scalable manufacturing capabilities, including our in-house cell therapy manufacturing facility, iCTC, Iovance Cell Therapy Center, in Philadelphia as well as additional capacity with contract manufacturers. Our 22-day Gen 2 manufacturing process has demonstrated a more than 90% success rate to date, and we have provided TIL to more than 500 patients as of today. And finally, we're building the infrastructure for commercial success, looking to build a fully integrated company from research to clinical, to commercial, to manufacturing. Have an experienced cell therapy team, on average, with more than 4 years of cell therapy experience and doing all the activities that are required for commercial preparation, some of which I touched on here, including focus on the authorized treatment centers and our IovanceCares proprietary platform. Thank you. Back to you, Mark.

Thanks, Igor. That was fantastic. We've got about 5 minutes left for Q&A. Just to kind of relay the most common question I get from investors with respect to the upcoming BLA submission, what can we expect the -- how will this news be communicated to the Street? I mean are we going to get kind of a press release once the filing is complete? Are we only going to get a press release once the FDA accepts the filing? What are the next few months going to look like, assuming this thing actually is submitted in the time frame that you've guided?

So Mark, thanks. That's an important question. So as you know, historically, we would communicate all the material information from this type of discussions with the agency when that information becomes available. And that's the principle we intend to maintain. So we'll not get into the specific details at the moment, but let me just assure you, as soon as we get information that's material regarding the submission, I expect the company will announce it.

Okay, okay. Fair enough. And then can you walk us through what steps have to happen before a subsequent filing in cervical can happen? You mentioned you're going to seek regulatory feedback from the FDA for the cervical program later this year. Like can you give us a little more granularity around that? And kind of like what are the rate-limiting steps between lifileucel's filing in melanoma and a subsequent filing in cervical?

Right. Thank you for that question. So as you know, the landscape in cervical changed somewhat over the past year with new first-line approvals of checkpoint inhibitor class. And so we've been in discussions with the FDA to craft an optimal path for advancing our cervical program to the BLA. And as you know, we've -- in our cervical study, we have Cohorts 1 and 2 cohort was post-chemo pre-checkpoint, Cohort 2 was post-checkpoint. So one area of discussion is how to -- is how can we leverage those data and what else may be required for us to enable a submission for cervical cancer. So that's the general area of discussions. Again, I will not be able to provide further detail right now, but that cervical remains an important focus area for us after melanoma, and we plan to execute on the FDA feedback. And again, once we have something that we can share publicly, we definitely will.

Okay. Maybe a nonregulatory question for you. First of all, congrats on getting the IND for IOV-4001 cleared. And we're looking forward to that program getting into the clinic, hopefully later this year. Now looking at the pipeline, it seems a little counterintuitive that you have a PD-1 knockout TIL product and you also have a PD-1 positive selected product in the pipeline. Just how do we reconcile these 2 programs that seem kind of very contradictory to each other?

Those are the difference. So the PD-1 select program, it's part of the manufacturing process where we select TILs that are positive for PD-1. And so they are, in a way, orthogonal. It's not that we're selecting only PD-1 positive cells for the TIL product and PD-1 select, it's part of the manufacturing process. And the rationale for the IOV-4001 for inactivating TIL is we expect it may provide similar benefit or maybe better than co-administering with anti-PD-1 checkpoint inhibitors. And I'd like to point you and the audience to the presentation that we will have at AACR next month where we will be sharing some of the preclinical data from the PD-1 inactivated, or we also refer to it sometimes as PD-1 knockout program, and showing the preclinical efficacy compared to checkpoint inhibitors. And those data look quite encouraging.

Okay, fantastic. I think we're just about out of time. I'm not seeing any questions coming in from the audience. So Igor, I'm going to let you off the hook. I think it's safe to say that you've got us all on the edges of our seats regarding the BLA submission. We're very much looking forward to it. And I want to thank you for the presentation today. Thanks, everyone, in the audience for listening in, and please feel free to disconnect.

Thank you, Mark. Thanks, everyone.