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

Good afternoon. It's now my pleasure to introduce our next fireside chat guest, Dr. Igor Bilinsky, Chief Operating Officer of Iovance Biotherapeutics. The format for this session is roughly 25-minute fireside chat, but we'll begin with some high-level overview slides of Iovance and its manufacturing capabilities before jumping into the discussion. [Operator Instructions] Igor, welcome. Please go ahead.

Thank you, Geulah. Great to be here, and good afternoon, everyone. So I'll start with a brief intro of Iovance and our manufacturing capabilities. We are a publicly listed company, and I'll be making forward-looking statements as part of this presentation and for a full disclosure of risks and uncertainties associated with investing in Iovance, please refer to our SEC filings. So Iovance, we're a global leader in innovating, developing and delivering TIL, or tumor-infiltrating lymphocyte therapies for patients with cancer. We have provided TIL -- manufactured on Iovance's platform to over 500 patients to date with the manufacturing success rate of over 90%. And our manufacturing process, what we refer as the Gen 2 process, is a 22-day manufacturing process. Our pipeline includes 6 active clinical trials in 4 solid tumor indications, and our development programs include 1 Breakthrough designation, 1 RMAT, which is Regenerative Medicine Advanced Therapy designation and the 3 Fast Track designations. We have an experienced and dedicated 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 of cash in the bank, which is sufficient -- [ expectedly ] sufficient to support the operations into 2024. And we are very focused on building a strong IP position in this area with more than 35 U.S. and international patents. Our partners and collaborators include some of the leading cancer centers globally, including the NCI, MD Anderson, Moffitt, Yale and others, as well as Cellectis, who is our partner for developing genetically modified TIL using Cellectis' TALEN technology. This is an overview of our pipeline, which includes clinical studies of TIL in monotherapy in melanoma, cervical cancer, non-small cell lung cancer and head and neck. The pipeline also includes TIL combinations with checkpoint inhibitors in the clinic in the same indications, melanoma, cervical, head and neck and non-small cell lung cancer. We're also developing a PD-1 selected TIL that's in the clinic. We have our third-generation manufacturing process in the clinic, which is a 16-day manufacturing process, shortening from 22 to 16. We -- in addition, we're developing PBL, peripheral blood lymphocyte therapy, which is in the clinic in CLL. And we recently announced that the first IND for genetically modified TIL was allowed by the FDA to proceed in March, and that's our PD-1 inactivated TIL program that we plan to bring into the clinic this year in advanced melanoma and advanced lung cancer indications. And in addition, we're developing IL-2 analog that's in clinical development. So what is TIL? TIL, it's tumor-infiltrating lymphocytes. It's an autologous cell therapy that we're developing initially primarily for solid tumors. It is an individualized treatment that allows for the immune cells, called TILs, to be expanded ex vivo and infused back to the patient. So in a healthy individual, when cancer cells are detected by their body by the immune system, the TIL come to the site of the tumor and want an attack and kill or suppress the tumor. In cases where cancer does prevail initially, the TIL have come to the site of the tumor. However, for various reasons, including the tumor microenvironment and others, TIL are overpowered and are not able to fully control cancer. So the TIL therapy process essentially takes a tumor sample from the patient, expands and rejuvenates patient-specific TILs, produces a cryopreserved product that is then shipped back to the academic -- to the treatment center, and the TILs are infused to the patients. And we target it to be a one time therapy, such as one -- one treatment as part of this therapy. This is an overview of our 22-day GMP manufacturing process. This technology was initially developed by Dr. Steve Rosenberg and coworkers at the National Cancer Institute, and we took the process and streamlined and shortened it, cut it roughly in half in duration from several weeks to 22 days. And to build and ensure our leadership in this field, we've invested in building our own manufacturing facility, Iovance Cell Therapy Center, or iCTC. It is a build-to-suit custom facility that's located in the Navy Yard in Philadelphia. 130,000 square feet, a result of our initial $85 million investment. We started manufacturing for clinical trials in the first set of clean rooms in the third quarter of last year. And clinical manufacturing is continuing here right now. And we are in parallel preparing for the BLA submission that we target in August this year, and also preparations underway for potential pre-approval inspection and then commercial launch. Having our own facilities was an important strategic decision for us, because it allows us to have much better control of the manufacturing capacity, the operational excellence and quality of the product that we produce and also potentially allows us to significantly reduce the cost of goods. And I'm happy to say actually the news just came out today -- the society -- the International Society of Pharmaceutical Engineering, ISPE, announced the winners of the Facility of the Year awards this morning, and iCTC received the award -- Iovance received the award for iCTC. So great news today. Literally announced afternoon in Europe this morning. There's a conference ongoing in Spain, and we've heard about it. So, very happy to hear. So where do we go from here in terms of the technology and manufacturing? There are several areas we're investing in, one is developing next-generation genetically modified TILs. And at the forefront of that is what we refer to as our IOV-4001 program, which is a PD-1 inactivated TIL, which received IND allowance from the FDA in March about a month ago. And we plan to bring it into the clinic shortly in advanced melanoma, in advanced non-small cell lung cancer. And that program is based on our collaboration with Cellectis, using Cellectis' TALEN technology. In addition, we are exploring additional approaches for developing stronger TILs with higher efficacy, and they include PD-1-selected TIL, as well as optimizing memory phenotype of TILs, such as optimizing CD1 -- sorry, CD39, CD69 double negative TILs. On the manufacturing process side, I already mentioned, shorter Gen 3 manufacturing process, which shortens the manufacturing time from 22 days to 16 days that's in the clinic, and also a core biopsy process that manufactures TILs from a tumor core biopsy instead of a tumor reception. And that is part of the LUN-202 clinical study. And finally, I already mentioned the IL-2 analog for developing currently in the clinic. So where do we go from here? The -- we've had a number of accomplishments in 2021. And 2022, we expect to be an important year for the company. The first and foremost milestone is our plan to file the BLA for lifileucel in advanced melanoma. We're working on that and on track for in August 2022 BLA submission. In addition, we expect to continue developing our pipeline, and these include sharing clinical data from the pivotal cohort 4 in melanoma. In non-small cell lung cancer, continue enrolling our LUN-202 study and also execute strategy for registration based on the [ OTA ] feedback. In cervical cancer, similar to continued development and execute strategy based on our discussions with the FDA to bring that program toward approval. Combinations of TIL with checkpoint inhibitors and pembro in particular, we are continuing to enroll the ongoing cohorts in various indications. And we recently announced that we plan to open a Phase III study in frontline metastatic melanoma, combining TIL and pembrolizumab potentially in the late 2022. Genetically modified TIL. I mentioned the IND allowed for IOV-4001, PD-1 and activated TIL and the research pipeline were continuing to advance as well as well as focusing on getting our iCTC manufacturing facility ready for the BLA and commercial launch and conducting similar redness activities at our contract manufacturers. So to summarize, Iovance, we're looking to target a large solid tumor market with a strong unmet medical need. The initial focus is on post checkpoint solid tumors, expanding into earlier lines of therapy and combination therapies in several solid tumors, including melanoma, cervical, head and neck, lung and also in CLL. We view this technology to be the potential first onetime cell therapy that's approved for solid tumors and plan a BLA submission in August 2022 in melanoma. And as part of this focus for this conversation, a lot of focus for us is on efficient and scalable manufacturing process, including our own manufacturing facility iCTC in Philadelphia that will supplement with capacity from contract manufacturers. And to date, we've provided TIL to more than 500 patients with an over 90% manufacturing success rate. So I'll stop there and make sure we leave some time for questions.

Great. So thanks for that overview. And so you touched on this a little bit, but can you discuss the CMC-related work that you're doing to support the planned BLA filing in melanoma? In particular, regarding issues like potency assays and issuing product quality and consistency that have been interest in the state of late.

So that's an important area. And the potency assays has attracted a lot of attention over the past weeks, it's really been central to what we do to prepare for the BLA submission. As part of that work, we've had extensive discussions with the FDA and reported just recently that -- we received positive feedback from the FDA about the potency assays matrix, including our new proprietary cell co-culture assay, that's included in the potency matrix. And we're working hard on that to prepare for the BLA submission. The other areas that are related to the BLA includes a PPQ Process Performance Qualification runs, that are essential for the BLA. I mentioned that we're working on those at our manufacturing facilities. And our overall plan is to proceed to a pre-BLA meeting in July of this year and then submit the BLA in August 2022. So about 4 months from now.

Got it. And so you mentioned some of those components. Do you have kind of insights from your interactions with the FDA in terms of learnings regarding manufacturing that you can apply to other programs? .

That's a great question. So taking the potency assay and potency assay matrix is an example, we have designed it to be indication-agnostic. So we expect it to serve as a template for other programs we have in development, with TILs and other indications. So we expect that to be scalable. And a lot of the discussions with the FDA, and the FDA overall has been paying a lot of attention to this area, in part because we're really trailblazing a whole new therapeutic modality for solid tumors. And in part because of their overall interest in cell and gene therapy. So they issued [ to drop ] guidance is just about a month ago. One is on CAR-T therapies and another one on gene therapies. And components of those guidance documents have a lot of relevance for what we do at Iovance. And I can't say we see a lot of surprises there, but it's good to see that the FDA is actually publishing those documents. And then one other item on the regulatory front. As you know, we brought Raj Puri on board as our Executive VP of Regulatory Strategy and Translational Medicine. And Dr. Puri was at the FDA for over 30 years, the last about 19 of which he was the Division Director of the Cell and Gene Therapy division of the FDA, that oversees TIL, CAR Ts and other similar therapies. So it's wonderful to have him on the Board. Here is a great addition to the team, and we expect him to be a very important driver of our regulatory strategy as we develop next generations of TILs, including genetically modified TILs for this in the future.

Great. And so regarding scaling, you mentioned scalability and the flexibility of the facility. So can you describe a little bit about the manufacturing capabilities in terms of doses per year at launch, the max capacity and how you envision scaling up in the longer term, as well as globally from a geographic standpoint? .

Of course, happy to. So we are planning iCTC to handle most of the commercial demand at launch, and we also plan to supplement it with our contract manufacturers' capacity, essentially to manage risk and better manage utilization. For iCTC overall, the facility has been designed to be able to provide thousands of TIL doses per year, so TIL for thousands of patients per year. And we have expansion capacity within the current facility. We also have options for expansion at the adjacent site to further scale up capacity as needed and when needed. iCTC is designed consisting of what we call flex suites and core suites. Flex suites are capable of producing advanced process material, and core suites are optimized for high-volume manufacturing, primarily for commercial manufacturing, to produce both our Gen 2 process and also potentially our Gen 3 process. As far as geographic coverage, so our initial focus for the regulatory submission is in the U.S., but we expect to follow closely with Europe. And currently, we are, of course, conducting clinical studies at both sites in the U.S. and in Europe. And we are supplying European sites from the U.S. manufacturing sites at the moment. And iCTC, one of the reasons for selecting the Philadelphia location for iCTC is proximity to the major airports and the East Coast, which makes it possible to serve Europe from this facility.

Got it. And so you mentioned some of the capability in some iCTC in your manufacturing facilities to work with some of your next-gen processes that process, like Gen 3, other components. Can you expand on how those programs impact the manufacturing process and any adaptations that are needed? And also building on that, how those changes tie into things like vein-to-vein time for your therapies?

So maybe to step back, initially, this technology was developed by Dr. Steve Rosenberg and team at the National Cancer Institute. We took Dr. Rosenberg's process and look to take basically the most important parts from it, but then optimize it and streamline it for manufacturing that is both centralized and also faster. So bringing it down to 22 days. And that's the core of our current manufacturing process that we use for the pivotal program in melanoma that we're going to submit for BLA later this year in August. We continue optimizing the process, so the Gen 3 further optimizes some of the elements of the process while also shortening the manufacturing time from 22 days to 16 days. That's -- and then the other dimension of optimization is some of the new technologies that I mentioned, including genetic modifications, making more potent TILs, optimizing TIL memory like phenotype. Each of those will require slight adjustments to the manufacturing process, but the manufacturing suites are designed in a way that they can accommodate all those changes in the process at iCTC.

And then regarding issues like vein-to-vein time, how did those process changes point into those type of factors from a patient standpoint?

So it's -- strictly speaking, it's not quite vein-to-vein because it's not CAR T. So it would be tumor reception.

Sorry, tumors to vein, you're right.

So if we go from, for example, Gen 2 to Gen 3 process, that pretty much shortens that infusion time proportionately, shortening it by about 6 days because we shortened the process. For the PD-1 inactivated TIL process, we haven't -- I'm not sure we've talked exactly about the cycle times for that, but it's fairly similar to the earlier processes that we're working on, in addition just adding the PD-1 in activation step by using TALEN. So that should not change the infusion time significantly. But we'll talk more about that I'm sure as soon as we start dosing patients, and we'll provide additional details.

Absolutely. So we've also heard about some supply chain constraints in cell and gene therapy as of the recent years. Can you tell us how you're managing supply chain issues in your facility?

So it's an important topic for us, especially as we are preparing for commercial launch and the scale-up of the volumes. We've been very focused on risk reduction and building a supply chain that is both redundant and reliable. And broadly speaking, it includes identifying redundant suppliers for some of the key materials, putting in supply agreements in place at -- guarantee supply and put conditions around that to reduce risk, stockpiling inventories more if we need to and using other approaches. So we've been very focused on that and the team and the supply chain is getting everything ready to ensure a successful launch as soon as we receive approval.

Got it. And then one of the other kind of themes that we keep hearing about it relates to efforts to reduce the cost and incorporating types of innovation to achieve that. So can you discuss in terms of manufacturer if there's any measures that Iovance is taking to further reduce costs? And for example, to what extent are things like automation coming into play?

That's a great question, and we are thinking about that because that's the future investments that will be essential for -- for this technology in the coming years. So there are a couple of dimensions that we're thinking of there. One is just a cost reduction by better efficiencies. And some of that -- some of those efficiencies can be achieved using those existing processes by having our own facility, which gives us much more control over the manufacturer compared to working with contract manufacturers. So that's one lever. And there are multiple sub initiatives that the team is working on, looking at each component of the manufacturing process and identifying how those costs can be reduced. But the other dimension exactly as you mentioned, is automation. And we're looking at -- 2 parts there. One is further closing the process that could be as close as possible end-to-end, and developing automation tools that could be applied to increase throughput and decrease variability, improve quality and ultimately reduce cost. And the cost reduction could come both from efficiencies, but also from require -- increasing the productivity of the manufacturing operators. And so that's something -- I hope to talk more about this once those efforts mature, hopefully, in a few years.

Got it. And in terms of the commercial launch and you talked about this a little bit, but are there any other GMP-related activities that you're engaged in, in preparation of the potential launch?

For the launch, let's say, 3 areas. So one is, first of all, BLA submission. A lot of focus on that. August is an important date for us. The other parts getting ready for a potential pre-license inspection or PLI, both at our facility at iCTC and our contract manufacturers. That's a big effort that's ongoing as well. And then getting the capacity ready for launch and the capacity includes both the facility and also the team, getting the team hired, the team trained and ensuring that we have the level of operational excellence. That's important for -- particularly important for autologous therapies where we need to get things done right first time. That's the mantra we use: Right, the first time.

And then just to end from a -- or a scale perspective, what key trend do you see emerging from regulatory agencies with regard to manufacturing of cell therapies? And how is Iovance positioning itself to stay ahead of that situation as it evolves?

So I mean that's a broad topic. I'm obviously happy to see the 2 drug guidances that I mentioned published by the FDA a couple of weeks ago, one is primarily focused on CAR T., but also has some elements that can apply to TIL and the other guidance on gene therapies, genetically modified therapies that also has applications to TIL, in particular, for our IOV-4001, PD-1 enactivated genetically modified TIL. So what's great is that the FDA is truly paying attention to this area and investing resources to get better understanding of the technology. And -- but the other part of that, as I mentioned, having Raj Puri on our team is really critical for driving our regulatory strategy and effectively working with the FDA, particularly on the new therapies that we're now bringing into our pipeline.

Great. So I see we're at the 25-minute mark, so I'd like to thank you again Igor for your participation. Congrats again on the award for the manufacturing facility.

Thank you so much. Thanks for having us.