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

Sure. We thought that the Moffitt study gave the kind of strong early signal that we needed to proceed with the study that we've designed. What you saw in the Moffitt study was durable complete -- durable responses, let's say, and complete responses in a small number of patients, of course, but in patients that were PD-L1 negative and in patients that, of course, had driver mutations as well. So we took that as a -- really, the way we think about setting up our total clinical trial pipeline is we work with collaborators a lot in early stages to get that signal, Ben, right? We do that with MD Anderson. We have trials with Yale in breast cancer and Moffitt, of course, in lung cancer and in other settings as well. So we use these early-stage signal-finding trials to provide us with the information, the data, allowing us to shape our own trials in a way that we think have the best chance of success. And so yes, we thought that data was very, very encouraging in the lung cancer space. I think our advisers and KOLs agree. And we just thought it was time for us to fully commit to a significant lung cancer trial and to do it now.

Okay. Okay. That's great. I guess, to the extent you can disclose at this point, how similar are the patients that are being targeted for the potentially pivotal cohorts of this study relative to the -- to, say, cohort, I think it's 3B of the basket study, i.e., the advanced disease?

Yes. 3B, well -- I mean, 3B in the basket study, I think, has patients that are further along in the treatment paradigm than what we've designed in our registration-directed study, right? We really tried to slot in our -- and I didn't make this point earlier, but the registration-directed study is really in the second line of therapy, right? It's after the initial chemoimmunotherapy that lung cancer patients receive, and we wanted to slot ourselves in, as I said, early on in the treatment paradigm, and that's second line, right, where the 3B cohort that you referenced is really for later line patients that have failed, I think, up to 3 different lines of therapy. And so those patients, I think, are further along and important patients, I think, to continue 3B as an effort to treat. But in terms of our own registration-directed trial, as I said, it's really directed against that second line population, which is really in between our cohorts in the COM-202 trial, right? We have early stage patients. We have late line patients. And then the lung 202 trial is really slotted in right in between those 2 patient populations.

Okay. Very helpful. You also mentioned that this study leverages the Simon's two-stage design. For those of us who are not super familiar with that, could you kind of just give us the high level as to what that is and how that helps you here?

Sure. Simon's two-stage is just a smart way when you're designing trials to give you a point along the way, a statistical point along the way, right, where you can kind of take a look at the data as it comes in and make decisions. And I think this is important from a drug development perspective, from a corporate perspective in terms of derisking these significant large number of patient trials. I think it's also important to reviewers and clinicians that are putting their patients on the trial, right, to understand that we're going to be looking at it along the way and making decisions in the best interest of patients along the way based on a statistical design that's kind of prebaked, right? That's already in the protocol for the trial that this is the way the decisions are going to be made around the trial. So I think it works for several different reasons, Ben. And I think we're not the only folks that use it. I think a lot of people in clinical development use the Simon's two-stage for the reasons that I've articulated.

Okay. Excellent. And then you've also kind of accrued some data on the third-generation manufacturing. I know that you guys started this in head and neck, and there's a cohort in this lung study utilizing that that you mentioned. Why not leverage that throughout the entire study?

I think that's a pretty simple one. We have so much data with Gen 2 right now, and it's such a robust process, it's a commercial process. I mean we're taking that into the BLAs for melanoma and cervical cancer. We have several hundred patients we've treated with Gen 2. We have transferred it into 4 CMOs. So it's just a process that we think is a commercial process and that we can apply across the solid tumor space. Now having said that, we're always thinking ahead, right? We're always trying to improve upon our manufacturing processes, not only to shorten the process to get the product to patients sooner, but also just to make more potent TIL, right? So -- and as you know, we have several processes now in clinical evaluation, right? We have our Gen 3 process, which is shorter, produces younger TIL, 16-day process versus 22. We have a selected TIL process that I think we've talked about that is now in clinical trials. We have a process for hematologic malignancies now that's also in clinical evaluation. And we're working on filing an IND for a genetically edited TIL process as well that we hope to have in the clinic at some point next year. So I think really, the answer to your question is that Gen 2 is a very good, robust process. And we saw no reason to kind of turn the dial in another way and kind of examine another variable. We just wanted to stick with what we knew and what we knew worked.

Perfect. Okay. Makes sense. So you also just presented some interesting data at SITC moving out the head and neck cancer. I guess I would ask, what are your next steps for this program? And then kind of going back to the previous question, is the path forward here with the third-generation manufacturing process in that setting?

Okay. The -- yes, first of all, the data that we presented at SITC. We're very excited about it. Obviously, it's a small number of patients, still only 9 patients, but a 44% overall response rate in this setting. Head and neck is a difficult-to-treat disease, no doubt about it. And at least this early data we were just really encouraged about. I think next steps are that we really need to enlarge the dataset and let the dataset mature, Ben, right? So we need more patients on this trial. And we just need longer follow-up to -- because DOR is important, right, duration of response. In order to have really the best package to sit down with the FDA with and design a registrational-directed program, I think you need a response rate in an unmet need population. You need that response rate to compare well to the other alternatives, of course. And then you need maturity of the data to show that not only do the patients respond, but there's a duration that is meaningful in terms of clinical benefit to the patient. So I think what you're going to see is you're going to see us to continue to add patients to that trial, to accrue patients to that trial, let the dataset mature and then take it where the data leads us, of course. We are looking at additional generation processes, Gen 3, you referenced Gen 3. We are looking that in our other head and neck cancer trial that we've been running for a while. It's 145-03. And so in that trial, which is later line patients, right, we were getting responses, but the duration of response we thought could be improved in the later line patients. And so that's why we moved forward in the treatment paradigm and started working with pembrolizumab, right, in an effort to see what the combination would do in head and neck. But in the monotherapy cohort in head and neck, we move to new generation processes, and that's what we're studying there. Because we do believe that these new generation processes have the potential, right, to create more potent TIL products. And so we want to try them in settings where we like to see the data improve a little bit.

Okay. That makes sense. And I appreciate that clarification. In addition, I think you also mentioned this earlier, you have a number of collaborations with sort of investigator-sponsored studies that are ongoing, generating data around TILs, one of which is MD Anderson. In addition to looking at ovarian cancer, I think you're also looking at colorectal and pancreatic cancer, which I thought was interesting. Have TILs ever been tested in those indications? Are those sort of first of a kind studies?

The answer is that the NIH, National Cancer Institute, whereas you know we licensed our original platform -- Steve Rosenberg and his colleagues there did study -- have studied TIL in numerous solid tumor settings. Obviously, the bulk of the dataset has always been in melanoma, in the HPV-associated cancers, like cervical and head and neck. But certainly, at the NIH, there have been small numbers of patients, right, treated in different solid tumor indications. And I think other academic sites have also produced this data outside of melanoma and cervical and head and neck cancer. But there's never been kind of large specifically designed studies, as far as I know, in other indications that have produced datasets that I think are meaningful. There have been kind of 1, 2, 3 patients treated, but it's really -- what we've been trying to do, obviously, is to expand with our collaborators into these additional indications and get enough data in enough patients, right, to have meaningful information that we can act on. And so that's been the purpose of MD Anderson, Moffitt, Yale. We have a collaboration now with the CHUM, the CHUM site in Montréal to do that for that reason.

Okay. Do you have a sense from MD Anderson or any of these other collaborators as to when they can make data public?

No. I really can't speak to that. I mean it's MD Anderson's trial. And yes, so I don't think we give guidance on the MD Anderson data. So I don't have anything now for you, sorry.

Okay. No worries. So I want to talk about one last thing, and that's the IL-2 analog, IOV-3001. I guess can you just kind of give us a little bit of background for that asset? And what needs to happen before this can move into the clinic? And I'd also love to hear sort of how you're thinking about which indications you would sort of target first at this.

Sure. Yes, we just licensed this novel IL-2 at the beginning of the year from Novartis. It's a high priority project for us, and we spent 2020 basically setting up the supply chain and the manufacturing of that new IL-2, with the intent of going into IND-enabling studies next year in 2021. So yes, we've made a lot of progress. 2021 is going to be about setting up, teeing up the IND. At the moment, I don't think we've set upon or just certainly disclosed any particular indication for that. Obviously, there's an opportunity to add it to the TIL regimen, I think, which does include IL-2 at the moment. But the clinical development plan, I think, is still an evolution. Right now, we're doing the blocking and tackling that we need to do to file the IND.

Okay. Okay. Great. And so I'm looking at the question board, I don't see any questions come through. Please throw them in if you have any. I think there is a little bit of a delay, but maybe last 1 for me just sort of a balance sheet question. I guess, can you just remind us of your current cash position and your expected runway?

Of course. Yes. As of the end of September, we had over $700 million in cash. We are fortunate to be able to raise over $500 million earlier in 2020. I think we're really well positioned to execute, to do what we need to do, which is to get the BLA for melanoma filed in 2021; to have the necessary discussions we need to have with the agency with respect to the cervical program to file an additional BLA; and to complete our launch readiness in anticipation of FDA approval. So I think we're very well capitalized at the moment. We have strong funding. We're applying those resources in those particular areas. But also continue to look forward in terms of clinical development into new indications. As we've discussed, the lung cancer trial is super-important for us, it's going to be a real focus in 2021. And then on the research side, as I also mentioned, it's always about making a cheaper, better, faster product, a more potent TIL product for patients that we can bring to next generation product life cycle management of our TIL platform.

Okay. Well, fantastic. I think we're out of time, Howard. Thank you so much for this discussion. And everyone, thank you for joining.

Thank you, Ben.