Status Update

Oct 5, 2020

Ladies and gentlemen, thank you for standing by, and welcome to the Iovance Biotherapeutics Regulatory Update. At this time, all participants are in a listen only mode. After the speakers' presentation, there will be a question and answer session. I will now hand the conference over to your speaker today, Ms. Sara Pellegrino. Please go ahead. Thank you, operator. Good afternoon, and thank you for joining us. Speaking on today's call, we have Maria Fardis, our President and Chief Executive Officer. This afternoon, we issued a press release that can be found on our website at iovance.com, which includes a regulatory update. Before we start, I would like to remind everyone that statements made during this conference call will include forward looking statements regarding Iovance's goals, business focus, business plans, pre commercial activities, clinical trial plans and results, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, collaborations, cash position and expense guidance and future updates. Forward looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward looking statements. With that, I will turn the call over to Maria. Thank you, Sarah, and good afternoon, everyone. This afternoon, we provided a regulatory update for our Till therapy Lifileucel in metastatic melanoma. In preparation for the planned biologics license application or BLA submission for Lifileucel, we have been engaged in discussions with the U. S. Food and Drug Administration or FDA, including a recent Type B meeting regarding the requirements and timing of certain information that would be provided as part of the BLA. We are pleased to have reached agreement with the FDA on the duration of clinical data follow-up for our pivotal Cohort 4 to support the BLA submission. We believe that the clinical data from our C1440 1 trial supports the potential for lifileucel in metastatic melanoma. As part of the Type B meeting, Iovance and the FDA were not able to agree on the required potency assays to fully define our Till therapy, which is required for BLA submission. As such, we are continuing to redefine and define the information from our current potency assays and simultaneously developing additional assays. As a result of these developments, our BLA submission is expected to shift from the end of 2020 to now occur in 2021. We will continue to work closely with the FDA during the next steps, which should be helped by the fact that FDA has granted Fast Track and Regenerative Medicine Advanced Therapy or RMAT designation to lifileucel in metastatic melanoma. Additional guidance on the BLA submission timing will be provided when available. I would like to highlight that we believe we have a strong data package from our C14401 trial supporting the potential for lifileucel as a one time treatment for advanced melanoma. Updated Cohort 2 data from this trial previously presented at the 2020 American Society of Clinical Oncology Annual Meeting or ASCO showed an overall response rate of 36.4% with a median duration of response not reached at 18.7 months of median study follow-up for 66 patients. Early cohort 4 data that we have previously reported showed an ORR of 32.4% at 5.3 months of median study follow-up with 68 patients. We think this is particularly remarkable in a study population where chemotherapy is the only current available option with a 4% to 10% response rate and a short duration of response. Collaborating closely with the FDA is our number one priority at the company right now and we will work as expeditiously as possible to address their questions. Before we head to the Q and A, I want to emphasize that we had a great team and we all continue to believe lifileucel has potential to assist many thousands of patients with a true unmet medical need in metastatic melanoma as well as other tumor types. With that, I will now turn the call to the operator to answer your questions. Operator? Thank Our first question is from Jim Birchenough with Wells Fargo. I guess just on the additional assays you're developing, I'm just wondering if you could give us some sense of timelines, are these assays that are readily available or that you need to build out de novo and how quickly could you generate those results? And I guess on the existing assays, is there some disagreement around just the quantification or measurement? And are you getting some specific guidance on what assays they'd like to see or what parameters? I'm just trying to get a sense of how much guidance they're giving you. Sure. Hi, Jim. Thank you. Good afternoon. Our assay is a well known potency assay that measures the production of cytokine by a Till product. This assay has been used for characterization of Till potency extensively. So, that information has been provided to the agency. A second assay has also been provided to them and the validation of that data is something we intend to provide to the agency. In terms of additional assays, yes, we are developing other additional assays in addition to the top 2 that are in the running to make sure that the agency has ample number of options in terms of the CMC package and the potency assay definition. And Maria, just so I understand, are those additional assays measuring different cytokines? I won't be able to go into too much detail as this is still subject to the cytokine based assay, it's like a cytokine based assay. The cytokine based assay. It's like a cytokine release assay. And then maybe just one follow-up in terms of adequate duration of follow-up that you agreed on with FDA, what is that duration of follow-up they're looking to see? Absolutely. It is 6 months from the development of PR as assessed by IRC, Independent Review Committee. Okay, great. Well, thanks for taking the questions and good luck with all that, Maria. Thank you, Jim. Thank you. Our next question comes from Ben Burnett from Stifel. Your line is open. Hi, thanks so much. I also want to just ask about the potency assays. I guess just two quick questions. The first one is, are these potency assays, would you expect them these assays to be used to define cells in other indications such as cervical cancer? So are there still work you're doing here, would this be applicable to the other indications? Thank you, Ben. Yes, I do. Once we define Till, that would be my expectation. Of course, this is subject to the discussion with FDA to assure that that confirmation is agreed upon by them as well. Okay. And then also just with regards to some of these additional assets that you're developing, do you expect there to be a notable difference in the amount of tumor sample that's needed to perform these various potency assays? And I guess is it possible that the tumor biopsy requirement could change as a result of this? I do not anticipate that. This is on the final product after we have released the product. So I do not anticipate an impact on the starting material. Okay, okay. Got it. Thank you very much. Thank you. Thank you. Our next question comes from Mark Breidenbach with Oppenheimer. Please go ahead. Hi, Maria. Thanks for taking the questions. So it sounds like you need to generate some new potency assay data to meet the FDA's request. I was just hoping you could confirm that you have archived cells from all of the Till batches that you made for the trial that you'll need to generate this data and that no additional clinical data will be required? Hi, Mark. Thank you for the question. Just to clarify, the request is to refine the information from the current potency assay. It's not necessary to go back and remeasure them. But yes, to confirm your question, we do have archived samples from clinical patients already to should that be necessary to go back and revalidate a new assay entirely. Okay, understood. And does this development impact at all your plans for giving The Street updates on clinical trials either from Cohort 4 in melanoma or from the cervical trial or any of the cohorts in your Basket study? It certainly doesn't impact in any way the Basket study or the cervical program that reminding ourselves we have just enrolled our last patient in the cervical pivotal cohort 1 and therefore that still has some way to go to mature that data. In terms of Cohort 4, in terms of data update, I don't presume that it would have an impact on the data reporting. The amount of follow-up is slightly longer than we had initially had thought about, but I don't expect any impact otherwise. Okay. Thank you. Thank you. Thank you. Our next question is from Reni Benjamin with JMP Securities. Please go ahead. Hey, good afternoon, Maria. Thanks for the update. I guess, I'm still a little bit confused and just trying to understand what exactly is the disagreements. Can you just give us a little bit more color? Is it are they asking for new assays? Or is there something are the numbers that are coming out of the assays maybe a little bit too wide in terms of confidence and they want it pretty narrow and so you're also giving them additional assays that they might be able to use? And maybe at the end of this when you submit the application, how many assays do you think you will need for potency? Thank you, Rene. Good afternoon. Yes, the primary focus from FDA has been our potency assay. We as well as our advisors and KOLs believe that we are using the best assay for this product candidate. But given FDA's request, we are certainly developing and validating additional assays. I don't know if we have necessarily agreed with the agency as to how many assays would be adequate. So, we continue making sure that we refine our information from our current potency assay, while we work on additional assays that we will provide to the agency. Okay. And then when we think you may have answered this, but when we think about timing, is this something that as you refine the assays, you're submitting it right away to the FDA so that they can provide you kind of regular feedback? Or is this something that you'll have to schedule another Type B sort of meeting, call it, 3 to 6 months from now and go over kind of all the data? I guess, how long do you think it will take for you guys to come to an agreement? Excellent. Thank you. We are submitting data live to the certainly recognize that CBER is very busy with COVID and additional other programs that they have before them. But we have been submitting our documents live to them and they have been responding. So, given that we have an RMAT designation and a Fast Track designation, we will continue with our pattern of providing data as we receive them, we compile them and we provide them to the agency. Whether there will be a subsequent meeting or not, I think that's subject to a discussion as to whether they feel that they have all they need or a dialogue would be necessary. So I think it's a little premature for me to comment whether any meeting would be necessary or not. Great. Thank you. Thanks for taking the questions. Thank you. Our next question comes from Nora Goldstein with Mizuho. Please go ahead. Great. Thanks so much for taking the question. Maria, maybe if you could just expand a little bit on I suppose the difference between what the agency is asking as it relates to the commercial product relative to what you had been using for your clinical product? Hi, Maura. Sure. Sounds good. We do have a panel of variables that we measure for our products in general. It is the norm as a sponsor is going into commercial landscape for those parameters to be tightened up, number 1 and number 2, revisited as to which ones of those will be used as a commercial release. So, there was a prior question, I think Mark was asking, do you have samples? There's additional assays that we have developed and we have been measuring along the way. I think the question at this point is which ones should be used in the commercial landscape. So yes, there's additional ones that we have used in the clinical landscape as well. Okay. If I could just ask, I mean procedurally, what happens if you do not come to agreement? Our immediate goal is to make sure that the agency is comfortable with what we are providing to them. So we will intend to carry on the dialogue and provide them additional assays. So, I prefer not to speculate what happens if you don't come to an agreement. This is a life saving therapy and I think the agency recognizes that that it's adding value to the arsenal of therapy for patients. Okay. Thank you. Thank you. All right. Our next question comes from Joe Catanzaro with Piper Sandler. Please go ahead. Hey, guys. Thanks so much for taking the questions here. Maybe first a real basic one, I guess, how are we defining potency here? I guess the obvious definition is just some sort of interferon gamma or cytokine release. But is it more complex than that? And is there any aspect of potency pre and post thawing and standing at room temperature? Anything you could add there would be helpful. Thanks. Absolutely. Hi, Joe. Good afternoon. Yes, so our assay is very similar to assays that have been used for CAR T products. What is unique about Till as you're aware is that this is a differentiated product in the sense that there's not a clear target for Till therapy, which is also part of the reason why Till work in solid tumors. There has not been a precedent for a specific target to be known for Till therapy. So that's the differentiator between a Till product versus, for example, CAR T products that has been recognized before. So the recognition assay is not something that is available for Till product because we don't know what we recognize as part of Till cocktail. Okay, got it. That's helpful. And I guess, maybe this is similar to an earlier question, but asked a little bit differently. But is there any impact potentially to patients treated in Cohort 4 and that maybe they were treated with TILs out of spec from a potency standpoint? I wouldn't look at it that way. The specifications for commercial are always tightened as part of the pre BLA discussion, as a matter of fact. In fact, historically, typically tightening of the specifications is something that happens during the BLA. So, in some sense, we are pleased that we are having this discussion prior to the submission. So, this is not out of the ordinary in any way to engage in a dialogue to define the specifications prior to getting the product in a commercial setting. It does not mean that the clinical product is invalidated if that's what you're asking. Okay, got it. No, that's very helpful. Thanks for taking my questions here. Thank you. Thank you. Our next question comes from Biren Amin with Jefferies. Please go ahead. Yes. Hi, guys. Thanks for taking the question. Maria, did you discuss with FDA whether you could file under the RTOR filing? Hi, Biren. No, we have not discussed that with them yet. Okay. And then, given you had the RMAT designation, which I think you mentioned allows for regular dialogue, I believe at the end of 2018 and possibly even in early 2019, the FDA and the company talked about potency assay. And so I guess the question is, was the assay not agreed to over the last 18, 20 months? Or is this after that dialogue a new request from the agency? Yes. We've been engaged in an ongoing dialogue with the FDA regarding the potency assay for some time. And we have had a path forward and but as part of this Type B meeting, it was made clear that FDA would require further refinement of the current potency assays data and the possibility of additional assays. So, as part of development, you certainly carry on a lot of dialogue with the agency. Okay. And then, I think one of the potency assays that you've looked at is interferon gamma in production. I think there was a SITC poster at the end of 2017. And I think in that poster, the company looked at measurements of 1,000 picograms per mL to demonstrate effector function. And so is that something that FDA has issues with? Because I believe in the paper, it calls for consistently greater than 1,000 picograms per ml. I can't provide any further detail in terms of the dialogue we're having with the agency they're in until we have we provide them additional data. I did note that they want us to refine the information we have provided to them. So that's an ongoing discussion with them. Okay, great. Thank you. I appreciate it. Thank you. Thank you. Our next question is from Madhu Kumar with Baird. Your line is open. Hey, thanks for taking our question. So following on about the discussion of TILs as related to CAR T that you don't have a target to go after. This relates to kind of the ability to demonstrate some kind of in vitro cytotoxicity that is not demonstrated by your favorite panel of cytokines? Hi, Madhu. Was that a question? Are you asking sorry, I couldn't catch the question. Can you ask me the question again? Yes. My question is yes. Is the issue that like with CAR T you have an array of you have a cytotoxicity assay you can perform because know whether your T cells kill a given target expressing cell, there's no equivalent for Till. So is this the assay that you can perform until we have to plan to go at? Thank you. Madhu, I'm having a really hard time hearing you. So I'm going to assume that you're asking about what's the difference between CAR T and Till. Is that what you're asking? So, if a potency assay for CAR T relates to toxicity against the given target, If you don't have a given target for Till's at that point that you have to demonstrate cytotoxicity without having to know target to go after, like how should that contribute to the issues between you all and the FDA? Yes. I think I understand the question. If I understood the question, yes, the fact that CAR T have a very clear target to go after makes it a little bit easier to define. And I think that's the challenge with Till, the fact that it doesn't have there's no precedent for specific target for a product like Till. So this is exactly what the crux of the discussion with FDA is. Okay. Then kind of practically if lipolusulin melanoma is going to get filed in 2021, does it get filed jointly with cervical and we don't have kind of the cervical data and it was mentioned earlier the potency assays largely overlap? Yes. I don't know the timing. We have not committed to a specific timing. We really will provide information when we have had follow on dialogue with FDA. If I had to think through sort of the indications, given that we have such a nice long follow-up on melanoma at this point, I still think that melanoma would be our first indication and given that cervical has just recently consented their last patient, we may or may not have enough follow-up. It really would depend on the timing of the BLA subsequent to discussion with FDA. But I understand your question and I think it's there's certainly an option to think about indications and sequencing them. Okay. Thank you. Thank you. Our next question comes from Peter Lawson with Barclays. Your line is open. Hi. Thanks for taking my questions. Maria, the assay that the FDA is asking for, would that be the do you think they'll need that as well for cervical cancer? Hi, Peter. Good afternoon. I do think that the same type of assays likely are going to be used for both indications. Just to remind ourselves, the product that we are manufacturing for both indications is GEN-two. It's the same manufacturing process and the same release. Okay. And then why do you think it came up now versus earlier? Is it kind of a change of heart by the FDA or change of reviewers or what do you think kind of drove that change? I think that as part of this Type B as we are discussing BLA, the questions are becoming very crystallized, very black and white that we are coming and here's the package. And so the agency needs to take a position at that point. And that's why I think this Type B meeting has been, sort of a definitive point for us. Do they have a good sense of the either the assay they want or the kind of the tolerances around those assays? Typically, the agency doesn't offer suggestions to the sponsors. The sponsors offer various options and the agency either agrees or disagrees. And then just a final question. The new assays, are they assays you're currently doing? Or do you have to you think create them from scratch? I see. We certainly have other assays before the agency and we continue providing additional information about those. At the same time, we are working on additional assays in house as well. Got you. Thanks so much and good luck with everything on that. Thank you, Peter. Thank you. Our next question is from Boris Peaker with Cowen. Please go ahead. Great. Thanks for taking my question. I guess first is on the assay impact on the turnaround time, would that have any make it any longer? And can you also remind us, if I recall correctly, you removed some kind of an assay to speed up the turnaround time. Does that have anything to do with this in any way? Hi, Boris. I don't recall removing any assays. In fact, we've added assays through the course of development as is ordinary for drug development. The anticipation recall that the existing assays that we have provided to FDA is still in discussion. We are refining the information that we are providing to them. We have also had additional assays that we have used as information and we are providing the validation data to FDA. So those already are in the play. There's no change in those assays. They're already being used in our clinical landscape. Does that help? Yes. So just specifically, it sounds like it shouldn't impact the turnaround time from sample collection to infusion back into the patient? Not with the existing assays. That's correct. Got you. I guess, maybe separately, as part of this meeting with the FDA, I mean, you discussed obviously the details of the assays. Did they provide any kind of feedback on the actual clinical data so far, whether that's sufficient or whether patient numbers or any kind of other assessment? In addition to the amount of follow-up, you mean? So we have agreement on the amount of follow-up as well as the fact that Cohort 2 can be supportive as well as Cohort 2+4. Is that what you're referring to? Yes. And also if they just said anything about efficacy, what sufficient patient selection, I mean, there's tons of criteria that they could look into the data set, if you've gotten any feedback on that? Not in that part of this Type B meeting, no. Great. And lastly, when is the next meeting set up to kind of to get future updates, at least from the investor perspective? When do you think we'll get future updates on this assay development? Right now, we are very focused on providing the additional data with FDA to the FDA and we will provide additional information as soon as we have them, we will update the investors. I cannot provide additional information. Great. Thank you for taking my questions. Thank you so much. Thank you. And we have a follow-up from the line of Jim Birchenough with Wells Fargo. Please go ahead. Hi, Maria. I guess a couple of follow ups. I guess first just on the potency assay, I guess I'm trying to figure out to what end might FDA want additional assays. And that sort of begs the question of what they're looking to correlate with. And so is there anything in your existing assays that could predict efficacy or predict lack of toxicity? I mean, ultimately, FDA wants to drugs to do harm and prevent do good and prevent harm. So is there something in that, that your assays currently are not predictive enough of efficacy without toxicity? Or is that any aspect of this? Yes. Thank you for the question, Jim. We do note that in current literature, there's no available for Till product that closely correlates with response to these products. So that's a challenge from a data perspective. We will continue our dialogue with the agency to provide them additional assays to make sure that they're comfortable with what we are providing them. But as of today, there's not particularly well known assays that are closely correlating with response for Till product. And then with the existing assays that you've put in front of FDA, is there a certain number of sales loss, so to speak? What proportion of sold product is not ultimately dosed? And is there any aspect of that in this that, FDA is concerned about criteria that might result in too few or too many failed lots? We did I guess as part of an assay you always disclose a specific number of patients that have been dosed or not. In other words, if there's OOSs, it's always part of a package. So that data is available to the agency. Is that your question? I guess, I'm just wondering if the assays that you put in front of FDA have been employed actually to screen patients for treatment. With CAR Ts, there is a certain number of manufacturing failures where they don't meet spec and they don't end up going to patients. Is there any of that data for TILs? Yes. As a matter of fact, we disclosed this as part of the ASCO section for Cohort 2. We did disclose that of the patients that are consented, there was 6% manufacturing failure and 12% of patients who had progressed and were not able to receive their Till product. So that 6% manufacturing clinical program. Got it. Okay. Maybe just on one separate topic. As this is getting drawn out a bit, what can you do in parallel to sort of make sure you've got a running start when you do ultimately get over this hurdle with FDA? Yes, great question. A number of our modules for the BLA are actually already ready. A number of them have been written. The reports are finalized and compiled. So, a lot of the prewriting of the documents have been done. And that certainly will help when we are ready to submit. A lot of that can just be dropped into the documents. So once we are able to address this with the agency and reach agreement, I think that the normal timelines can be a little shorter in this case because a lot of the documents have been written. Got it. Well, thanks for taking follow ups. Thank you, Jim. Thank you. And I will turn the call back to Maria Fardis for her final remarks. Thank you again for joining the Iovance conference call today. Please feel free to reach out to our IR team if you had any follow-up questions. Have a great day. And with that, we thank you, ladies and gentlemen, for participating in today's program. You may now disconnect.