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

Good afternoon, everyone. This is Biren Amin, biotech analyst here at Jefferies. I'd like to welcome everyone to the Jefferies Healthcare Conference, I'd like to introduce our next company. We have high Iovance Biotherapeutics and their CEO, Maria Fardis; as well as CFO, Tim Morris. This is going to be a fireside chat format. So if anyone wishes to ask management a question, you can feel free to e-mail me [email protected].

So thanks, Maria, for joining us this afternoon or morning to you, I guess. Maybe just if you could go over just top line, in terms of updates in the melanoma and cervical program, just the time lines around those product programs and when we can expect data from Cohort 4 in terms of the IRC review data as well as cervical and when we can expect data from that cohort.

Sure. Thank you, Biren, for inviting us, much appreciated. We are going to be talking about our melanoma cervical program, and I know we will be interested in talking about non-small cell. In terms of our melanoma program, as you're aware, we have read a very early cut of the data of 68 patients from 89 patients that were enrolled into the melanoma program. And as part of a financing, we released that data just recently. In terms of additional data flow from that particular cohort in Cohort 4 we likely would target a medical conference for additional data regardless of whether it's all the patients, longest follow-up or IRC readout, and that would depend on when that information will be available. We have not made a commitment that, that necessarily would be in the remaining part of the year. We just presented our Cohort 2 data at ASCO. We were very encouraged to see not only the response continued at 36% ORR with a very heavily pretreated patient population who have all seen prior anti-PD-1 as well as anti-CTLA-4, but we also showed that median duration of response has not been reached and that was highly encouraging from our perspective. We also showed that a sub-analysis for various subpopulations showed very little sensitivity to prior therapy with anti-CTLA-4 and/or BRAF, if the patient has a BRAF patient. So in totality, we're very excited about what we are seeing so far from Cohort 2 data. On Cohort 4, as I noted, we have presented preliminary data. We will continue the patient follow up and we are in dialogue with the agency in terms of the timing of pre-BLA meeting and the registration plan. Moving to cervical. We briefly -- I know you asked a question about it. I did commit to continuation of enrollment into the cervical program and completion of the enrollment expectedly by around midyear for the entire pivotal program. Release of data is expected possibly later part of this year. But we want to be sure that we have spoken to FDA in terms of our registration program and that they are in agreement with our amount of follow-up. Just to highlight, we initially had thought that both of these programs are going to be co-terminus in terms of their enrollment completion. And what we saw was quite a significant degree of expediting time lines in our melanoma program, we ended up enrolling that program in 3 months ahead of schedule, allowing us to read the preliminary data as we released just about a week ago as part of the financing. Does that answer your question?

That does. So that was really helpful. And I guess just on the Cohort 4, can you share in terms of just baseline characteristics, whether they were similar to Cohort 2 and also, maybe if you could just comment on the PD-1 refractory population in terms of what's the typical response rate in DOR that one would see? Because you clearly had some phenomenal duration response data with Cohort 2? And then I guess, lastly, did you enroll any patients that received PD-1 as adjuvant therapy before coming to the trial?

Sure. So let me comment on kind of refractory patient population that you asked about. We actually released this data for this subpopulation in SMR meeting in 2019. We were highly encouraged to see this response rate for this patient population was over 40%. We do think this is a high unmet medical need from a clinical perspective. These patients get diagnosed with metastatic melanoma and they've been receiving their standard therapy, which is anti-PD-1. And since they are considered primary refractory, the patient population that has a progression or PD as their best response. Very quickly, they continue having any clinical benefit. And so they're in need of therapy. And so that patient population seems to be a really great patient population for till they respond quite well. The median DOR has not been reached, and the data was highly encouraging. In terms of adjuvant setting, did you dose any patients that are adjuvant sort of we have received checkpoints as an adjuvant setting. We have defined patient population for us as a patient that is metastatic melanoma and has received prior systemic anti-PD-1 as well as BRAF or MEK, if they have a BRAF mutation. Therefore, we are already in second line metastatic. But you're making a very good point that's a the potential patient population that someone can consider, and it's really not in the equation [Audio Gap] before most people, they may not recognize that, that absolutely is an unmet medical need patient population as well. We are not enrolling those patients, but I recognize what a significant market opportunity that is and how [ 2 ] could possibly add value to those patients.

That's great. And then I guess, what percentage of the patients in Cohort 2 had extensive visceral disease. Can you just comment on that? And could we expect similar patients in Cohort 4?

Yes. So we did not break down our patient population by visceral disease, but as you are aware, the patient population is quite extensively pretreated. We did disclose that over 40% of our patients have liver as well as brain [ MEK ]. So that displays what an advanced patient population it is. We also did say that their baseline disease burden is about 10 centimeters, which is imagine a grapefruit. And this is only a target lesion some of parameters, some patients have frequently more than that as well. What I can comment on [ the ] Cohort 2 plus 4 or versus Cohort 4, it appears that the patient population is fairly comparable. I want to be careful about drawing too much from the data we released, we only have 68 patients that we have read out. And we didn't put a lot of the details. We're really trying to present them as a part of an upcoming conference at some point. But at a very high level, the patient population was quite comparable between Cohort 2 and Cohort 4. And what we saw was with the amount of follow-up that we had, we had very comparable response rate between cohort 2 and cohort 4 as assessed by investigators.

And you mentioned that you're going to have a pre-BLA meeting on melanoma fairly soon with the FDA. Can you just go over what you hope to discuss with FDA at the pre-BLA meeting? And what you hope, I guess, to get out of it?

Sure. So the purpose of a pre-BLA meeting is typically to get agreement with the agency on at least 2 big buckets of questions. A bucket is procedural, for example, FDA would like to know where are you putting what data? What are you going to provide? Which module is it going to be in? Who is going to review this module? So there's always a procedural component to pre-BLA meeting. And then there's a component of scientific data exchange. And here's the data we are going to give you, here is what it's going to look like? Do you agree this sufficient number of patients? Do you agree this is the patient follow-up? So this is the interaction we were having, a pre-discussion to pre-BLA with the agency where they requested to see the available data. And so we cut the Cohort 4 as part of this early look just so that FDA has some visibility as to how many patients and how much follow-up they likely would see as part of the pre-BLA. So the pre-BLA has a procedural component, and a scientific component, in the scientific component, 1 discusses clinical, CMC, nonclinical, all of that is on the table for a dialogue with the agency.

And I guess as part of this pre-BLA meeting, are you also going to discuss the potential for eligibility under the RTOR pilot? Are you aware of this RTOR pilot? We had a company -- and this is I think for oncology drugs, where they allow BLAs or NDAs to be filed in sections and the FDA will review those as those sections are submitted. It's unlike a rolling, where rolling is submitted, but only after the last section, does the FDA began to review. So are you going to have that discussion where you asked the agency to be able to file under an RTOR pilot?

Yes. So it's a real-time review as opposed to a [ rolling ] review. I'm aware of what you're referring to. Without disclosing too much about our regulatory strategy, there are components of this BLA that we are negotiating that can be provided as the agency has received the package. So that's not unusual. It's not anything unreasonable from my perspective. In my past life, I've done this repeatedly, and the agency has been open to receiving some components while they're reviewing. It is subject to negotiation as part of the pre-BLA, and there shouldn't be significant updates. The agency prefers to receive bulk of the data upfront. So yes, we're aware of that, whether we are using that designation or not, I'm not commenting on, but as part of any BLA, particularly for single-arm, it's not unreasonable to provide supplemental updates while the agency is reviewing the document.

Okay. That's perfect. And that's actually really helpful. And then I guess, you mentioned that you hope to present the data at a medical meeting later this year. What type of a follow-up would you need from all patients before you would present the data? Would it be 6 months? Like I think you previously discussed that you at least want to have at least 6 months follow-up for all patients. Or is it a different time [ part ].

Yes. Just to be clear, I'm not committing that we are presenting at a medical meeting later this year. There's 2 considerations that one has to think about. We want to make sure that we are in a very solid scientific venue, a number of the meetings are moving around or turning into virtual or sometimes are getting canceled. And also second part of the year, it's a little bit more difficult for solid tumor indications. So we haven't decided exactly what medical meeting. So depending on the timing of that particular medical meeting, we probably can assess how much data follow-up on how many patients we have.

Okay. And then I guess in terms of commercialization plans, can you just talk about them? Are you starting to bring in marketing team and laying down, laying out, I guess, commercial plans? And have you done market research? If you can share anything on what you think adoption would look like in the refractory melanoma setting?

Yes. Absolutely, our current size of our commercial medical offers, parts of the organization is 14% of the size of the company. We are around 190 employees. We do intend to double our commercial team by year-end. I have talked about -- so we already have a very expensive, and adequate size of a commercial organization. We started doing market research well over a year ago, as a matter of fact. And what has been remarkable is we need to update our market research as our median DOR continues to evolve and not reach. So it's been nice to have to update those market users numbers and assessments and market update as our median DOR continues to mature beautifully. In terms of sort of how we think about commercializing the product, we have a very patient-centric model. We make sure that we intend to assure that the patient and the clinical site is very well prepared. Our cell therapy account managers or CTAMs are going to be very much engaged with our clinical sites. Many of these sites already have been part of our clinical program. I have noted before that we have well over 20 sites for each of the indications of melanoma and cervical participating in our clinical program. So they're very familiar with them, and they're very familiar with cell therapy process and administration. We intend to continue expanding that footprint for the commercial landscape, and we certainly have a phased plan in additional sites in first year and second year. So yes, we have a very detailed plan, market research already in place. We understand the patient population very well, and the market opportunities remains very exciting from my perspective.

And what are your thoughts, just on the reimbursement landscape because the CD19 CARs, they clearly ran into issues with Medicare. Do you foresee that you would run into similar issues with Medicare? It seems on the commercial side, they are reimbursing the CAR-Ts on a case-by-case basis. So that doesn't seem to be an issue there. And I guess what percentage of your population are Medicare that are in melanoma and cervical?

Yes. We certainly as part of our market research, we look at the patient population, who will be on commercial insurance versus potentially Medicare supported insurance. We are working very closely with CMS as a matter of fact and we have had preliminary meetings with CMS as well as other health insurance providers to introduce our product and make sure that they understand that we are coming into this space. To kind of step back a little bit, cell therapy landscape and coding and coverage, have had some very positive movements. And so I'm very encouraged to see that CMS recognizes the cell therapies are here to stay and they've made good move in creating additional codes, starting for CAR-Ts, and NTAP has made favorable move to increase coverage. I think that the commercial landscape is actually very well improving. And we have the other CAR-T therapies that have reached the market. So thank for that for defining the landscape and continuing to work very closely with the payer body to assure that this product and cell therapies, in general, are well reimbursed. So we continue having very close dialogue with the payers, whether it's commercial or CMS, and we've had very favorable interactions and we continue very actively engaging with the payer landscape as well as other methods of reimbursement, including NTAP.

So you're also evaluating melanoma in fronts as part of the basket trial. Can you just talk about the basket study, where you are in terms of enrollment? Or when we can next expect data from each of the cohorts. Frontline melanoma is clearly one of them. You've got lung, which you mentioned, also in that basket. So if you could maybe just provide a status update on that trial, I think that will be helpful for the audience.

Absolutely. So it is a basket study called IOV-COM-202. This program started approximately a year ago it's 5 cohorts into this study. There is melonoma, as Biren noted, head and neck and non-small cell lung cancer and from an indication perspective covered, 3 of the cohorts are early line patients. So it's TIL plus KEYTRUDA that is being offered. And 2 of the cohorts are late-line patients and 1 is non-small cell [Audio Gap] relapse/refractory with TIL alone; and 1 is the melanoma cohort relapse/refractory patients with the new product we have introduced into clinic, which is a PD-1 selected TIL. In terms of where we are with an enrollment, I just want to be clear that when we started basket study, it doesn't mean all cohorts get activated at the same time, the cohorts get active at different times. It's very reasonable to think that we had already a footprint with sites in melanoma in head and neck. So those cohorts get activated first because we already had contracts in place, and we were active with some of these sites already for our other programs and lung was a little bit of a late comer. I have not committed to a data flow point yet. We want to make sure that we have sufficient data and enough follow-up for us to understand exactly what Iovance still does in that indication. I'm sure you're aware that this data, a Moffitt TIL data was presented at AACR where very exciting responses were seen in non-small cell lung cancer patients. Who were relapsed or refractory to prior nivolumab and many of them had received their TKIs if they had an oncogene driver mutation. So the next up for us is to understand what those Iovance TIL do in a relapsed/refractory patient population in non-small cell. And of course, as I noted, we have a cohort that is in PD-1 naive patient population, where we are offering TIL plus KEYTRUDA. So I'm not committing to a specific data flow time frame. But we are very excited about non-small cell, we are very committed to the indication in addition to our ongoing basket study. I've also committed as part of our financing to start a registration-enabling program in non-small cell. So that's something we're also working on simultaneous to continuation of our basket study.

So the registrational non-small cell study, in what form would that take place? Would this be a randomized design? Would it be a single-arm? Can you talk about patient numbers and endpoints that you would need? And I guess you would have to have some data from the basket cohort to support that Phase III trial and some assumptions around that. Is that a fair assumption? Or -- so can you just talk a little bit about this Phase III design? I think this would be interesting to the audience.

Sure. So I just want to make sure that I'm clear. Is registration targeted, it doesn't necessarily mean it's Phase III. And I just want to remind that at Iovance, we have done it now twice, where we have defined a very late-line and unmet medical need patient population. We have treated them with TIL in case of melanoma, and both cervical as well, we had a Simon's 2-stage design, where we started with a defined unmet medical need patient population. We administered our TIL and along the way we decided whether we have an adequate response to proceed and expand the cohorts. So I can imagine a similar type of a design, you haven't disclosed the specifics of either the patient population or study design. But I guess what I'm trying to say is we absolutely can think about unmet medical need patient population. There's multiple in non-small cell. One can imagine multiple cohorts in a study where TIL alone is getting administered to unmet medical need patient population with a type of Simon's two-stage where 1 expand if you see an adequate response, which is predefined. And if it's not -- if we don't see that response that we are satisfied with, we don't have to expand that particular cohort. So that strategy absolutely is something that we can explore and we intend to continue thinking about in non-small cell. Our commitment in that indication is absolutely very strong, having seen the Moffitt data.

And the study would start this year?

I'm sorry, Biren, what was that?

Would the study start this year?

I don't think I have disclosed quite what the timing would be, but it is a very high priority for us to initiate a program -- a second program in non-small cell, yes.

And I'm going to assume -- I mean, you mentioned that EGFR mutations post Tagrisso and TKIs, you saw -- clearly, we saw a signal from the Moffitt data would it be fair to assume that, that's one of the cohorts that you would look at given it's a high unmet need.

There are definitely patient populations within EGFR mutation subgroup with which is clear unmet medical need. TKIs have added significant value for patient care in frontline non-small cell, particularly if the patient obviously has a driver mutation, which sort of allows for TKIs to be adding value. But nonetheless, in the patient population, there is absolutely unmet medical need group that really would benefit from alternative therapies. So that's definitely one of the cohorts I'm thinking about.

Great. And then I guess on head and neck, this is also part of the basket. Earlier this year, you disclosed that you're going with a 16-day process as well as a PD-1 select TIL. Can you just talk about what led you to evaluating both of these TILs compared to, I would say, the current generation of TILs that you're evaluating in melanoma and cervical.

Sure. People may remember that we had disclosed some very preliminary data in head and neck, about a couple of years ago as part of the financing. We were very excited to see a signal from an ORR perspective, but we really were hoping to see a better duration of response. The duration of response we were seeing was around 3 to 7 months, and the patient population was particularly difficult to treat. We were seeing patients that had, as an average, 4 or 5 prior lines of therapy, the median priors was around 3 to 4. So we have done a number of things in that patient population. We redesigned the study to have prior therapies limited to 1 to 3 prior lines of therapy, trying to get a patient population that has some degree of health left in them to be able to be treated. We also thought about what else can we do to help with treatment. We introduced Gen 3, which is a 16-day manufacturing product. We felt that this product could have younger TILs and maybe better potency in terms of addressing a more aggressive disease and a PD-1 [ select TIL ] product, which also has a better potency expected from preclinical data in head and neck. So that was the goal. The goal was to introduce a more potent product for head and neck patient population as well as try and get patients that have slightly better life expectancy before we continue the study. That was the intent of introducing those 2 products in head and neck.

And for each of the cohorts, I understand that you have different time lines but at what point would the company say, okay, we're comfortable in disclosing data? Is it after -- for 10 patients, 12 patients? Is there even in a bar that you have? Because we're anticipating data from this basket cohort all the time. So I just want to, I guess, understand what the company's threshold is before they start to disclose data from each of these cohorts.

We have not again -- I have not committed to anything on the head and neck either. I think that this actually would have even a higher bar because I want to see some degree of durability. We know that there's some ORR associated with our product, but really the key would be durability, do we have a durable product. So I really don't want to commit to a time line for head and neck either...

Sure.

Thank you. But I want to be sure we understand are these new products adding any significant values over our Gen 2 or not. That's -- that's what how we're thinking about it.

Okay. I've got, I think, a minute left and I have to wrap up. So a question, that background, is it PD-1 select TIL or is it a Gen 1 TIL.

It is Gen 2 TIL. Thank you for that question, though.

All right. Well, on that, no, I'm going to wrap up. I want to thank you, Maria. Thanks for taking time out this afternoon. Really helpful discussion.

Thank you so much.

We're going to stay in touch, thanks.

Thank you, Biren. Much appreciate it. Thanks, everyone.