Iovance Biotherapeutics, Inc. (IOVA) Earnings Call Transcript
August 11, 2020
Earnings Call Speaker Segments
Great. Thank you, Sara. So, exciting time.
Wanted to know a little bit about your thoughts on uptake. How complex is the actual TIL delivery process? Do you have a sense of which hospitals can handle this? Are they the same CAR-T hospitals? Do you have the same sort of expected side effects? Just your thoughts around the original uptake, who's going to be comfortable in the early stages?
Sure. So we are partnering now with the leading U.S. cancer centers to prepare for the launch of lifileucel. We are targeting about 40 clinical sites at launch. A lot of these sites have had experience directly with TIL as part of our clinical studies. And as you mentioned, because CAR-T is also a more complex process that has certainly done a good job of paving the way for us to enter into these centers with TIL therapy.
And do you sense you're competing for CAR-T beds?
Well, it is a -- there are different types of patients where CAR-T is approved versus where we are developing TIL for. So it's unknown if we would be competing for CAR-T beds.
Interesting. And any hints as to what changed as you generated or you shortened the manufacturing time? Presumably, you're driving these cells. You have to be careful not to exhaust the cells. Is that where a lot of the IP is? Increasing growth rates without exhausting cells?
Well, that is actually -- that is part of the process is that we are able to generate the TIL in this 22-day process. And then through cryopreservation, we're able to preserve those cells that are grown until they're ready for infusion.
Okay. Got it. And I don't know if you're public. What fraction of patients can you make TILs from? Is that -- is it very tumor dependent because you have a lot of experience in 2 tumor types now?
So that's a great question. With our Gen 2 process, we have treated over 300 patients across all of our clinical studies and our manufacturing success rate across those more than 300 patients is above 90%.
And is there an initial screen before you begin manufacturing? Or is that 90% of patients who might benefit from the therapy?
So yes. So in order to receive TIL, you have to meet the inclusion criteria for our clinical studies.
And is that a performance status inclusion criteria or is that the fact that you can biopsy a certain amount of tumor?
Well, the good news about TIL is you don't have to be too focused about the location of the cancer. Because these are metastatic patients, sample target lesion can be identified from various places in the body.
Got you. Got you. And do you expect to become sort of more R&D-focused, I'd say, I talked to a lot of companies trying to engineer TILs, do things like that. I mean you have essentially a similar manufacturing time. Do you expect to get into that business where you would do things like remove PD-1 from the TILs? You must get that question all the time. Or maybe do an RNA approach? Is that a big part of your future?
Yes. So we're already looking into that, and that is part of some of our earlier-stage research initiatives. So we have an agreement with Cellectis where we are using the TALEN technology for genetic modification of TIL. That could be potentially very exciting, although still very early. And in terms of PD-1 selected TIL, that is actually in the clinic. We added a cohort of PD-1 selected TIL into our ongoing clinical study in head and neck cancer. So basically, with that, the TIL are selected for PD-1 in the beginning of the process, and then those are the TIL that go on to the rest of the process.
So you select PD-1 low TILs. Is that what...
Yes.
Okay. Got it. Okay. And on the delivery front, I mean this goes way back to Rosenberg. You're using IL-2. It looks like it's -- most of your toxicity the CAR-T cells started there and got rid of it. Your thoughts on whether you will need IL-2? And have you thought about partnerships for some of the less toxic IL-2s?
So our current experience with our adverse event profiles are highly consistent with onetime treatment are largely related to lymphodepletion, IL-2 and the stage of disease that the patient has. And most of these occur right around the time that the treatment is administered and then they go away rather quickly. So that is the good news. On the IL-2 front, we actually are working on an IL-2 analog. Also earlier in development, but that is preclinical. And so we are looking at the potential to develop potentially better IL-2.
And you're going to do that yourself?
That's correct.
A pile of them floating around. Okay. And then just the basic idea of doing this almost -- melanomas, people who've been blasted with IL, most of them have had ipi and nivo or almost all of them have had nivo and a lot of them have had ipi as well. And now you're trying to look for patients that will support an immune response. Any thoughts of trying to get into less experienced patients? I understand you have to start here to get a -- to develop a cancer drug. But what are your thoughts about trials in patients that might have a little more intact immune systems that might support this approach a little better?
Theoretically, that's definitely a possibility. And when Rosenberg first published his data in melanoma, it was on earlier melanoma patients.
Interesting. So I was going to skip to that. So the -- your data are certainly good, but the NCI data are better, right, Rosenberg's experience. Is that a fair comparison? Does he have very cherry-picked patients? I mean he had a 56% response rate and a 24% complete response rate. Is that an unfair comparison? Or do you think you could get there as you optimize.
So as I pointed out before, the patients that Rosenberg was looking at were much earlier in their disease. So that patient population is not necessarily comparable to our patient population. The treatment options for patients with metastatic melanoma, who have progressed on immune checkpoint inhibitors are very limited. If chemo is the available care, it offers only about a 4% to 10% response rate and median survival of only 7 to 8 months. If you look at the Cohort 2 data that we have reported to date, that was an overall response rate of 36.4%, and median duration still not reached after 18.7 months of median study [ by a lot ].
I got you. And then our next look at Cohort 4, I just want to make sure I have this correct. You've reported on 68 patients. There are significantly more in the trial and the rate-limiting step for us to see more data is agreement with the FDA on what you need to file?
So we've reported the early Cohort 4 data. And you're correct. That was in these 68 patients who had at least 2 available assessments by investigator. And in that cohort, we saw a 32.4% overall response rate at 5.3 months of median study follow-up. We said on our second quarter earnings call last week that we anticipate presenting more detailed data from Cohort 4 at a medical meeting in 2021.
Okay. And that would be the rest of the trial or just based on the cutoff to the medical meeting? Where are you in terms of completing that trial? Did you say that?
Sure. So the last patient in that study was dosed in January.
Right. Okay. Okay. And then just a few questions on cervical cancer. It's a more visceral disease. They're likely to be sicker. Is it harder -- is it -- what is the fraction of patients that can handle the IL-2? Is it a bigger deal in these patients?
No. So, so far, it has not been an issue. At ASCO 2019, we reported initial cervical data from our pivotal cohort. That was in 27 patients. The ORR there was a 44% at median study and median duration of response not reached at 7.4 months. And in those patients, IL-2 had not been an issue. A median of 6 doses had been administered in that group.
Got it. And then we all saw the Moffitt TIL data, and then you quickly got involved. Is that part of the Iovance model? Because I'm sure there are a large number of academic efforts that won't be able to build the manufacturing and optimize it. Do you see that as a significant business development opportunity to sort of become the partner of choice for what I'm sure will be a lot of academic efforts?
Sure. I think that's a great way to look at it. We have partnered with a lot of academic institutions, and we do have several studies going on with those academic collaborators, including Moffitt and MD Anderson. I think it's a great way for us to see some initial data and some initial signal finding and new indications. So that we can then choose which things to prioritize and invest in going forward. And Moffitt is a great example of that as the data coming out of the Moffitt TIL lung cancer study informed our own strategy to look at 2 cohorts of lung cancer in our ongoing basket study. And we are also planning to initiate a pivotal registration supporting study in lung cancer by the end of this year.
And any complexity with lung cancer? Are the biopsies harder to get?
Well, as I mentioned before, they wouldn't have to necessarily resect tumor from the lung as these are metastatic patients. The physician can identify a target lesion elsewhere if they want to.
Okay. So you're not worried about taking a distant mass. You have good luck with that? The argument is that metastases can be genetically different than the base tumor.
I don't think that's a concern.
Okay. And then last question in CLL, is that an important direction for you? Is it worth it outside of Richter's transformation?
So it's -- what we're doing with that study, it's basically a proof-of-concept study for our PBL therapy, not necessarily the lead indication that we would go after. But we really want to see how our process is working in terms of taking a 50-milliliter blood sample from the patient and growing cells during a 9-day process that we've developed.
Got it. Got it. Well, thank you very much. Unless you want to make a closing comment, I appreciate you coming by, giving us the update. So we've been talking to the companies chasing you for 2 days now. So it's nice to hear your version, and we thank you for presenting.
Thanks for having me. Thank you.
Thank you, Sara. Take care.
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