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

Excellent question. Yes. So for later line, what we see is still about 7,000 patients are dying in U.S. due to metastatic melanoma. And what we are also seeing is beyond checkpoints. Once the patients progress on checkpoint therapy, we really don't have a lot of good options available for patients. This is precisely why the physicians currently keep the patients on checkpoint therapy, even if the patients may be progressing because there's not a lot of options, unfortunately, once they progress. So from a commercial perspective, we do think there's still an opportunity to assure that we offer patients a better therapeutic option. Whether it's late-line or earlier-line, we're looking at both of them. Then we also take the opportunity to move to your other of the question, which is we are moving into earlier line. And specifically, as we move to ICI-naive or immune checkpoint inhibitor-naive patients, they're offering TIL in combination with various checkpoint inhibitors. And head and neck in melanoma and non-small cell, we have cohorts where we are offering TIL in combination with KEYTRUDA. And we have recently added a cohort in non-small cell, where we are offering TIL and ipi/nivo, which would be sort of a chemo-sparing regimen. So yes, absolutely, I do believe that the safety profile of the product allows for earlier line investigation in combination with checkpoint inhibitors.

Okay. Will you be able to present some of those data this year potentially?

So we presented the data on head and neck in SITC 2020, about 3 months ago. We had 9 patients worth of data with about 8 months of follow-up. It was very encouraging to see TIL plus KEYTRUDA in second-line or most of the patients were second line post chemotherapy. We saw a 44% response rate and a median duration of response that had not been reached for this small sample size. We have expanded that cohort to get more patients and additional follow-up and really look forward to having those patients to be able to definitively sort of decide what the ORR and final DOR would be based on that cohort. You're correct that we have 2 other cohorts that are enrolling right now, melanoma and a lung cohort. We haven't committed to a specific data flow, but we look forward to having sufficient patients to be able to present the data, of course, publicly. We think this may be a very exciting area for TIL to generate data that is really helpful for earlier-line patient population.

Understood. Great. And then a question on your cervical cancer program, which is another -- more of the -- another advanced program. You are in a pivotal study at the moment there. Just remind us of your strategy here and how we should think about the path to market?

Excellent. You're correct. And in fact, we thought about the same strategy that maybe a single treatment of TIL in patients that have received their available care would be -- allow us to have a single-arm strategy for registration. When we started this program, chemotherapy was GOG-240, was frontline standard of care for cervical cancer patients. The landscape of care is changing. We actually have seen KEYTRUDA get approved in second line post chemotherapy with a 14% response rate. And what we are seeing is that KEYTRUDA combination with chemotherapy may become a frontline standard of care. That clinical program is underway. I would expect that, that might be just the frontline strategy, ultimately, for treatment of cervical cancer patients. With that, we have 2 cohorts in our cervical cancer program. Our first pivotal cohort was the discussion with FDA with patients that were second-line metastatic post chemotherapy. And as we are seeing the landscape change, we are thinking our Cohort 2 may also be supportive of registration. Our Cohort 2 was patients that are post anti-PD-1. So it's possible that both of these cohorts may be requested by the agency, and we actually just finished enrollment into our Cohort 2, and we think this may be a very strong package for not only today's patients but the patient population that will emerge in about a year or so.

Okay. Fantastic. And on head and neck, we just touched on that, the data that was presented recently at SITC. Just how should we think about next steps in head and neck?

Yes. So we definitely -- I'm looking forward to this. As I noted, we expanded the patient population, the number of patients to be enrolled in this cohort. We want to make sure that we understand the actual ORR, the DOR with a larger number of patients and longer follow-up and figure out what is the strength of data. One can think about a cohort of this nature in 2 ways in terms of registration. If the data is significantly better than single-agent KEYTRUDA in second line, which, again, the response rate is approximately 16% for KEYTRUDA in second line. And we are -- we think we can statistically separate ourselves. There is a possibility of a single-arm strategy. However, any time you go into a combination, one has to think about a randomized study in order to register. So there's a very high likelihood that we would have to think about a randomized study before we think about registration of this regimen.

Understood. And then you mentioned there's some academic data from Moffitt that was presented in lung cancer recently. Again, remind us of the key takeaways from that, and how we should think about next steps potentially there.

Absolutely. So Moffitt had enrolled a number of patients. The way they designed the study is the patients would come in, they get resected. The patient then would start on nivolumab. And once they progress, then their TIL would be provided to them. So many of these patients -- so all of them have received nivolumab. They are post-nivo patients. Many of them might have received their TKIs if they had a specific oncogene driver mutation and some were treatment-naive. So there was a bit of a mix of the patient population. Nonetheless, of the 12 evaluable patients that they had, 3 were responders, 2 were CR and 1 was a PR. We really were impressed by both the magnitude of the ORR and the durability of the responses that we saw in these patients. What was also particularly remarkable was among the responders were patients that had a PD-L1 expression level of either 0 or low levels. And so that's highly encouraging. It allows us to think about TIL therapy for patients that have a low expression levels of PD-L1. This is precisely why we then went forward to design a study. Not only we have a few cohorts that are relapsed/refractory and early-line patient population, but we also designed this study, IOV-COM, IOV-LUN-202, where we ask for the patients to be second line post chemo immunotherapy. We are also separating the cohorts by PD-L1 expression of maybe less than 1% and bigger or equal to 1% because we think that less than 1% patients may be quite an unmet medical need. And it appears that TIL seems to be working for patients with low PD-L1 expression. By the way, we have seen this phenomenon in melanoma as well before. The patients with low PD-L1 expressors were equally responsive to TIL therapy. Now melanoma is not particularly sensitive to PD-L1 expression, someone, it is sensitive, but we think this is definitely an area of opportunity for TIL therapy.

When you think about an indication like lung cancer, there is, obviously, a lot of patients with that. And in context of other potential treatment options or novel therapies that are being developed, what percentage of patients do you think might be treatment candidates for TIL or cellular therapy?

I don't know if I can answer that question quite yet. I think that a lot of times when we start with a program, we first think about, well, what is the clinical response? If the -- I mean it's risk-benefit. So what is the benefit that you're always generating for these patients? If your benefit is really high and unmet need is there, then physicians are more inclined to administer the therapy. So it's a bit more of a risk-benefit question that I don't know if you have enough information to be able to answer it. Does that answer your question? Is that what you're asking about? I think we are a little bit in the dark in terms of what exactly will we see from a clinical efficacy perspective.

Yes. Yes. I guess, maybe asking a different way, sort of what response rate or improvement do you think might justify use more and more cellular therapy as opposed to chemotherapy or some other novel agents potentially?

Excellent. Okay. You're right. From the patient population perspective, we have chosen patients that typically, they have run out of their treatment options. If they are to be treated in the commercial landscape, one would expect docetaxel would be their available care. Docetaxel's ORR in about second-line patients, depending on, of course, the line of therapy and how we define them, is approximately 9%. And so from a threshold and the primary endpoint perspective, we think that meeting a docetaxel threshold should be adequate.

Okay. Very helpful. And then earlier, you did mention the build-out of your manufacturing facility. Just help us understand maybe what your product capacity, manufacturing capacity is right now, what it might be in a few years? And how we should think about cost of goods?

Thank you. From a capacity perspective, right now, in a clinical landscape, we have disclosed that we have dosed over 400 patients. We dial up or dial down our manufacturing capacity, really based on supply and demand. So we forecast because we are in a CRO. And of course, we don't want to necessarily pay for suite fees if you're not going to use them. We have a dedicated suites that we take over. We also take dedicated staff. So we dial that up and down as necessary very carefully. In terms of our own facility, the Iovance Cell Therapy Center or ICTC. The facility itself is fairly large, it's 136,000 square feet. It can provide product for thousands of patients, and the capacity can be dialed up or down based on 1-shift employees, 2-shifts employees or 3. And there's additional space that we can sort of add. Right now, we are not building the entire facility. We've taken a phased approach into what is really needed, and then we expand the facility if necessary. So I think we probably can provide sufficient material for depending on the indication that we are pursuing, certainly for the relapsed/refractory melanoma and cervical cancer patients that we are pursuing. In terms of COGS, just to summarize a little bit, COGS is a function of how much facility costs we're paying. So it's variable as long as we are in a CMO. It would be a little bit more fixed when we are in our own facility. So we haven't been sharing a specific number, but what I can share with you is when we compare to CAR-T products, we are not using viral components. So there's a little bit less complexity, although the product is autologous, so that high-touch product is still part of the equation.

Very helpful. And then last question before we need to close, what opportunities exist to potentially develop next-gen TIL therapies? And do you have any activities ongoing in that respect?

Yes, absolutely. So there are definitely multiple ways of thinking about next-generation products. We have been thinking about selecting subpopulations of TIL. And in fact, we have introduced the product into clinic, which is a selected TIL based on literature that was out there showing that this could be a better product. We are thinking about genetic modification. We have been collaborating with Cellectis and their TALEN technology, trying to think about how to modify TIL, including PD-1 knockout, for example. And we also think about process optimizations that shorten the manufacturing process, including our Gen 3 manufacturing, which is a 16-day process or using a core biopsy. And both of those are being rolled out as part of our IOV-LUN-202 program into clinic.

Great, maria. With that, we need to close. Our time is up. It was great to have you on this year's conference, and thanks for joining us.

Thank you for having me.