Earnings Call: Q4 2019

Feb 25, 2020

Good afternoon, and welcome to the Iovance Biotherapeutics 4th Quarter and Year End 2019 Financial Results Conference Call. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session and instructions will follow at that time. Please be advised that the call is being recorded at the company's request. Now, I would like to turn call over to Sarah Pellegrino, Vice President, Investor and Public Relations at Iovance. Please go ahead. Thank you, Laurie. Good afternoon, everyone, and thank you for joining us. Speaking on today's call will be Maria Fardis, our President and Chief Executive Officer Frederick Finkenstein, our Chief Medical Officer and Tim Morris, Chief Financial Officer. This afternoon, we issued a press release found on our website at iovance.com, which includes the financial results for the 4th quarter and year ended December 31, 2019, as well as a corporate 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, licensing and collaboration agreements 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'll pass the call over to Maria. Thank you, Sarah, and good afternoon, everyone. I am pleased to leave today's conference call to summarize the tremendous progress made at Iovance during 2019 and highlight recent updates and important milestones to come in 2020. I will also comment on our progress toward a planned biologics license application or BLA submission for lifileucel and LN-one hundred and forty five this year as well as preparation for the commercial launch in 2021. In 2019, we continued to advance our TIL tumor infiltrating lymphocyte therapy in pivotal programs in melanoma and cervical cancers. We also initiated Phase 2 clinical studies for multiple indications in solid tumors. In addition, we have introduced our very first peripheral blood lymphocyte therapy or PBL into clinic as a new approach for blood cancers. I'd like to begin with an update on our loose Till therapy, lifileucel in metastatic melanoma. As a reminder, melanoma is a common type of skin cancer accounting for approximately 96,000 patients diagnosed annually and 7,200 deaths each year in the United States. We announced last month that we have completed patient dosing ahead of schedule in the pivotal Cohort 4 in our C14401 study of lifileucel. This pivotal cohort was initiated in March of 2019 with a target enrollment of 75 patients. We currently plan on allowing all patients from cohort 4 to be followed for 6 months before data cut for inclusion in the BLA. We have started the process of assembling documents to be used for the BLA. We plan to meet with FDA and expect to submit the BLA in late 2020. As a reminder, lifileucel has received both Fast Track and Regenerative Medicine Advanced Therapy or RMAT designations from the U. S. FDA, which was supported by the clinical data from Cohort 2 in the melanoma study. The protocol for Cohort 4 was designed to enroll the same patient population as Cohort 2. We presented data from Cohort 2 in the melanoma study several times over the last year. The most recent update on overall response rate or ORR was presented in November at the Society For Immunotherapy of Cancer or SITC Annual Meeting. We reported a 36.4 percent ORR in 66 patients who were heavily pretreated as assessed by investigators. The duration of response or DoR for Cohort 2 has not been reached at the time of SITC presentation. In a recent Iovance corporate update in January 2020, DOR was still not reached at 15.5 months of median study follow-up. Published data shows median overall survival in late stage melanoma patients may reach 7 to 8 months, so the results with Lisoleucil are highly encouraging. We continue to monitor the patients in this study and hope to provide additional updates from Cohort 2 in 2020. Iovance as an organization is very focused on the advancement of this program toward preparation for the BLA. Our second pivotal study is LN-one hundred and forty five in patients with metastatic cervical cancer. We continue enrolling in the C14504 study and remain on track to complete dosing approximately mid year 2020 in the pivotal part of this study. Target enrollment is 75 patients. We are still planning to submit a BLA later this year following a dialogue with the FDA. Submission of the 2 BLAs are not dependent on each other and each indication may be submitted separately. During 2019, LN-one hundred and forty five received breakthrough therapy designation or BTD as well as fast track designation from the FDA. These designations were supported by compelling data demonstrating a 44% ORR from 27 patients in the ongoing study, which was presented at the American Society of Clinical Oncology or ASCO Annual Meeting in June of 2019. We also successfully completed an end of Phase 2 meeting with the FDA in 2019. Following the meeting, we increased target enrollment for the pivotal part of this study to 75 patients in order to support registration of LN-one hundred and forty five. We also added new cohorts in earlier and later lines of cervical cancer patients in anticipation of changing landscape in this indication. This specifically includes a cohort that allows for treatment with ELN-one hundred and forty five in combination with pembrolizumab and a cohort with patients who have failed prior anti PD-one therapy. During 2019, we dosed more than 150 patients in our clinical program. Our 2nd generation or Gen 2 Till therapy manufacturing process continues to be a robust one and with a demonstrated success rate of well over 90% in approximately 300 patients. In parallel with the pivotal trials for melanoma and cervical, we are already building our international and internal manufacturing capacity. Specifically for launch, the initial commercial supply will come from our CMO partner, WuXi Aptex Philadelphia facility as we continue to build our internal Iovance manufacturing capability. Construction of the Iovance commercial facility started in June of 2019 aiming to build a state of the art 136,000 square foot commercial scale production facility in Philadelphia continues. The new facility is expected to be operational by year end 2020, 2021 to support commercial supply in 2022. The expected capacity is planned to meet demand for thousands of patients. In anticipation of launch of lifileucel and LN-one hundred and forty five, we continue expanding our commercial and medical affairs infrastructure. Our main area of focus remains ensuring a positive patient experience with lifileucel. Towards that, we are working on the following items: clinical site engagement in preparation for commercial launch development of a close collaboration with healthcare professionals or HCPs who will be handling and administering our product, operational excellence by Iovance in provision of the product and communication with payers. In the United States, we currently work with over 20 clinical sites for melanoma and approximately the same number of sites for cervical. We anticipate that centers with prior Till experience and those with key opinion leaders in melanoma and cervical cancers will be initial target for the launch of Lifileucel and LN-one hundred and forty five subsequent to approval. Our medical affairs team is in place to work with a network of treating HCPs and patient advocacy groups to assure that information about Till is available to interest of organizations. We also continue optimizing our logistics and infrastructure to assure a patient focused organization is in place not only for our clinical program but also for commercialization. We have made great progress in identification of centers that we work with in the clinical program and expect to collaborate with them in the commercializing Till. On the patient access and reimbursement front, we have initiated discussions with private payers and CMS to ensure timely access to Till therapy for patients. And under a patient centric model, we intend to support the patient at every step of the way in the process from initial resection to infusion. As our market research and commercial preparation continues, we look forward to providing updates on our launch plan throughout the year. I would like to ask now our Chief Medical Officer, Frederick Finkelstein to provide an update about our other clinical programs and ongoing research at Iovance. Frederic? Thank you, Maria. I would like to begin with the expansion of our ongoing CE-fourteen thousand five hundred and three clinical study in head and neck cancer, which remains an important indication for Iovance. We continue to enroll patients in our CE-one hundred and forty five-three study and recently added new cohorts to the study. Patients in the first new cohort will be treated with LN-one hundred and forty five manufactured with our new proprietary 16 day 3rd generation Till therapy process which we call Gen 3. The 2nd new cohort will evaluate a selected Till product PD-one Select designated as LN-one hundred and forty five S1. We presented preclinical information on PD-one selected Till at SITC in November 2018, which demonstrated improved tumor cell killing properties for this product. This cohort is the first time we are testing selected Till in the clinic and we look forward to enrolling patients in these new cohorts. We have also made significant progress in evaluating the broader potential for Till treatment in earlier lines of therapy for checkpoint naive melanoma, head and neck and non small cell lung cancer. Patient dosing in the AOV COM202 clinical study, which we also refer to as our Basket study was initiated in May 2019. Three cohorts will evaluate TIL plus pembrolizumab in patients who are immune checkpoint inhibitor naive with melanoma, squamous cell carcinoma of the head and neck and non small cell lung cancer. In the 4th cohort, LN-one hundred and forty five monotherapy is offered to relapsed refractory non small cell lung cancer patients. Enrollment across all four of these cohorts is proceeding well and we have plans to add a 5th cohort to investigate our selected TIL LN-one hundred and forty five S1 melanoma patients who have received prior anti PD-one and BRAF or BRAF MAC if indicated. This is the same selected pill products that we have introduced into the head and neck study. The additional cohort will also increase the overall target enrollment in the basket study. Moving on to our peripheral blood lymphocyte therapy or PBL therapy, we are very excited to be in clinic with our very first Iovance cell therapy for blood cancers. I am happy to report that last week we dosed the first patient in the clinical study of our PBL therapy, which we have designated IOV 2,001. The Phase onetwo study named IOV CLL-one is currently enrolling patients with relapsed or refractory CLL or small lymphocytic lymphoma, SLL, into the Phase 1 dose escalation portion. We generate a polyclonal population of PBL for therapeutic use from 50 milliliters of blood using a 9 day T cell IOV-two thousand and one PBL therapy is a result of internal research and development efforts at Iovance to translate our experience with Till and solid tumors. We think this study will provide important proof of concept for our PBL approach and look forward to enrolling additional patients in this study. Before I turn the call to Tim, I would like to briefly mention our earlier stage research and development efforts. As announced in January, we have obtained a license from Novartis to develop and commercialize an antibody cytokine engrafted protein referred to as IOV-three thousand and one as a targeted and selective IL-two analog. IL-two is a major component of our treatment. So the development of a proprietary IL-two analog is a valuable opportunity to further optimize the beneficial properties of the IL-two through improving pharmacokinetic and pharmacodynamic properties as compared to currently available IL-two. We are also exploring genetically modified Till with the potential to create an even more potent Till. Under research collaboration and exclusive worldwide license agreement with Selectus, we have licensed certain Talend technology to develop genetically edited Till in several cancer indications. The worldwide exclusive license enables us to use Talend technology to address multiple gene targets to modify Till for therapeutic use. I will now hand the call over to Tim to discuss our financial results. Thank you, Frederic. My remarks will address the high level financial results from our Q4 and full year 2019. Additional details can be found in the press release that we distributed earlier as well as our annual report on Form 10 ks to be filed shortly with the SEC. Net loss for the Q4 ended 2019 was $63,600,000 or $0.50 per share. This compared to a net loss of $32,600,000 or $0.27 per share for the Q4 2018. Net loss for the full year 2019 was $197,600,000 or $1.59 per share, compared to a net loss of $123,600,000 or $1.27 per share for 2018. Research and development expenses were $54,200,000 for the Q4 2019, an increase of $26,800,000 compared to the $27,400,000 for the Q4 2018. Research and development expenses were $166,000,000 for the full year 2019, an increase of $66,200,000 when compared to $99,800,000 for the prior year. The increases in the Q4 and the full year over the prior periods were primarily attributable to an increase in costs associated with manufacturing activities and increased capacity, clinical trials due to higher enrollment and the growth of the internal research and development team. General and administrative expenses were $10,900,000 for the Q4 2019, an increase of $3,400,000 when compared to $7,500,000 for the Q4 2018. General and administrative expenses were $40,800,000 for the full year 2019, an increase of $12,400,000 compared to $28,400,000 for 2018. Increases in the Q4 and the full year over 2018 were primarily attributable to the growth of internal, general and administrative team as well as higher IP legal costs and market research activities in preparation for commercialization. At December 31, 2019, we held $312,000,000 in cash, cash equivalents, short term investments and restricted cash compared to $468,500,000 at December 31, 2018. In addition, as Maria mentioned, we are building our own iovance manufacturing facility. We expect to invest approximately $85,000,000 over 3 years for equipment and construction. I will now hand the call back to Maria to review upcoming milestones and to kick off the Q and A session. Thank you, Jim. Thank you all for attending the call today. We look forward to an exciting and productive 2020. In closing, our anticipated milestones for this year include last patient to be dosed in the pivotal program for LN-one hundred and forty five for cervical cancer, pre BLA meeting with US FDA, melanoma top line pivotal data and BLA submission. Before we begin the Q and A session, I would like to remind everyone that Iovance does not comment on speculation in the media and will not answer questions related to any articles circulating in the press. I will now turn the call over to the operator for any We have a question from the line of Jim Birchenough from Wells Fargo. Please ask your question. Yes. Hi, guys. Congratulations on all the progress. I guess thinking ahead to the commercial opportunity, just wondering if you think about the 7,200 patients that die each year of melanoma and if you thought about the addressable population that could benefit in cervical cancer. Could you talk about the initial target population of 20 plus centers for each and what capacity they have to treat these patients? And then I guess the second part of it is, what are the gating items to really making this more broadly available and how are you going to go about accessing that? Sure. Hi, Jim. Thank you for the question. From a commercial opportunity perspective, although unfortunately 7,200 patients die in the melanoma landscape and one can consider Till certainly an option for these patients, we are actually thinking about second and third line. And that patient population is broader than 7,200 that is currently reported. So that's how we are thinking about sort of positioning the product and that's the patient population that our current protocol allows. In terms of the centers, I just want to make sure that I'm clear. We are not targeting just 20 centers. The comment I made was we start with the sites that have been participating in our clinical program and those have been around 20 for melanoma and cervical. We certainly intend to expand that by the time we are getting ready to kick off the product in the commercial landscape. And I guess the question, Maria, just to follow-up, when you think about those initial centers that have had the most experience with Till therapies, do you have a sense of what proportion of the melanoma patients they treat? And how many more sensors do you think you need to gain experience to get more broad access to that second, third line opportunity? Yes. We do know exactly what is the distribution of patients in terms of where the bulk of them are. We certainly have an internal map. We consider where they typically go to receive their care. I don't know if I'm quite ready to speak about that specific plan, but we certainly think about it in the same way as you're approaching it. And just a quick one, Maria, is the cervical filing, the LN-one hundred and forty five filing, something you expect to get done in 2020 or does that really depend on when mid year you close out enrollment and could that slip into 2021? Right. We recognize that the timing of cervical and melanoma are slightly apart. We currently continue to plan for cervical submission by year end. And you're correct that some of that would depend on exactly when cervical enrollment will complete as well as the dialogue with FDA. But the current plans remain to go ahead and submit assuming of course all of the milestones are met around later part of 2020 as of now. Great. Well, thanks for taking the questions and congrats again on the progress. Thank you, Jim. Your next question comes from the line of Ben Burnett from Stifel. Please ask your question. Great. Thanks so much. I had a question on the IOV COM202, that's the basket trial, looking at Till plus pembro as well as the 4th cohort monotherapy. I guess, do you have an expectation as to when we might get data for these first four cohorts? Hi, Ben. Thank you for the question. We started patient dosing in May of 2019. Given that the study is a basket study, the patients may be distributed between the cohorts. We really would like to make sure we have a handful of patients in each cohort before we can report them. So we have not committed to a specific timing for data flow from this study yet. Okay, understood. Thank you. If I could just ask one more on the regarding the recent Novartis collaboration, can you talk more about the non Treg activating IL-two antibody that's being developed? I guess, how has the antibody been engrafted? And I guess, what makes this a more selective IL-two? Thank you. Sure. Yes, of course. So as you might know, IL-two binds to 3 different subunits alpha, beta and gamma subunits on various T cells. The beta gamma subunits is what we are interested in. The alpha subunit is more prevalent in binding towards Treg. We are trying to rule that binding out. So the CDR that we have does not allow for this particular IL-two to bind to the alpha subunit. It in fact focuses it better on the beta gamma subunits. That's why we expect it to be better. Okay. And I guess at this point, can you comment on just kind of the architecture of how the antibody is engrafted or is that at this point, is that proprietary? It's certainly proprietary and thank you for understanding. Okay, okay. Makes sense. Thanks so much. Thank you. Your next question comes from the line of Joe Pantginis from H. C. Wainwright. Please ask your question. Hi, everyone. Good afternoon. Thanks for taking the question. Maria, I was just curious if you can provide a little more detail with regarding your strategy for the evolution of your manufacturing share the responsibilities between these two facilities? And also when your facility comes online, do you anticipate that that will start off with Gen 3? Joe, to correct your statement, it would start off with Gen 2, correct? Is that what you said? Right. Thank you. Yes. And when it would evolve to Gen 3, sorry. Yes. Right, right. So we currently our commercial plan is very much locked and loaded for Gen 2. The facility is very much designed around Gen 2. Of course, it can support other manufacturing processes should there be a need for them. But right now, we very much are planning on our commercialization with Gen 2 process. In terms of roles and responsibilities, we already have started building our team out in Philadelphia. Certainly, the building itself requires a number of staff who are familiar with the process. We have great expertise in house, starting from our engineering team as well as people who are very familiar with the process and in terms of process development and optimization. So we already have a team that is slowly ramping up to what is going to be needed by the time the commercial activities rollout. In addition to the local team members in Philadelphia, we have additional team members such as quality or otherwise in San Carlos who are supporting the activities for the facility. So I don't foresee a sort of a switch on where everybody then 100 people are hired and they go into the facility. I see a rollout and the rollout has already been started. No, that's really helpful. Thank you. And if I could just ask a quick follow-up on your research front. With regard to the PBL program, obviously, it's exciting that it's a much shorter process and how you can identify these tilts. Just curious, is there any major difference once you extract T cells from the blood, are there any major differences between Gen 2 and the Till identification process before you expand them in the PBL versus Gen 2? We have a very different process that we use for PBLs. There is and again, some of that is proprietary and bulk of it has not been sort of shared already. So yes, there's rather significant differences. The cells, the T cells that we usually harvest from tumor are not in a very high concentration in blood. We are already familiar with that. We know that they are difficult to find. So we had to implement different procedures in order to fish these cells out and we were very successful obviously in doing so. But yes, there's differences and how we get the cells from the source, one being a tumor, one being blood. That's great. Thanks, Maria. Thank you, Joe. Your next question comes from the line of Mark Breidenbach from Oppenheimer. Please ask your question. Hey, guys. Thanks for taking the questions and congrats on the progress. Maria, I noticed that the pivotal cohort in melanoma enrolled a little bit faster than maybe you had initially projected. And the circles maybe more or less on the timeline you had initially projected. I'm just wondering if you can point to any specific factors that are contributing to that discrepancy. And also, is it safe to assume we would want a minimum of 6 months follow-up once the pivotal cervical cancer completes enrollment before we would see top line data from that? Thank you, Mark, for the question. Yes, you're correct. Melanoma enrolled faster than we expected. And I think that definitely shows a clear unmet medical need. The cervical landscape is definitely changing. As we are aware, there's earlier line KEYTRUDA studies coming into this space, both in terms of clinical trials as well as just the commercial use. And so the patients that we are enrolling into our Cohort 1, certainly the nature of the patients that are out there is changing. So it's really due to the change in landscape. Now we anticipated that this is going to happen and I made a comment about it. We had added 2 other cohorts into our LN-one hundred and forty five study for cervical in anticipation with the change in landscape. So we have thought through this and we have some alternative strategies if this continues. In your second question in terms of the 6 months of follow-up, we thought about a 6 months of follow-up from melanoma just because enrollment closed so early and it allows us to do a 6 months of follow-up. There has not been really a request either from agency or otherwise for a certain amount of follow-up. So I think that this is really a subject to discussion with U. S. FDA in terms of how much follow-up they might be asking for. But I do want to note that the 6 months is a Iovance proposal in the melanoma case. Understood. And maybe just a quick follow-up on the Gen 3 process. I'm curious why this is really initially being focused in head and neck. Maybe you could elaborate a little bit on why it's important to have a faster manufacturing timeline in head and neck. And I'm also curious with regard to the PD-one select version of Till, what is that what was the impact of that on manufacturing timeline? Does that add several days to the process? Okay. Thank you. Yes, we had recognized earlier on that the patients in head and neck cancer have a fairly short survival unfortunately. So we felt that a shorter manufacturing process really could benefit a patient population that doesn't many times they don't make it to the first assessment or a second assessment. So that's why we implemented that initially into the head and neck study. The PD-one selected process does not add additional days to the manufacturing process. It is in fact we have optimized that process so that it is not longer than our Gen 2. So it's the same duration as our Gen 2 process. Okay, understood. All right. Thank you for answering the questions and congrats again. Thank you, Mark. Your next question comes from the line of Ren Benjamin from JMP Securities. Your line is now open. Great. Thanks for taking the questions and congratulations on the progress. Maria, can you just talk a little bit about how many patients do you think are required per cohort before you feel pretty comfortable with disclosing the results, not just from the basket, but maybe some of your other studies? You mentioned duration in an answer to Mark's question, but what other kind of gating items need to be discussed with the FDA prior to filing? Right. Thank you, Ben. I don't think there's a magical number for us to disclose, but I prefer if you're, for example, at least 5 patients before it would be kind of nice to talk about. But there's not a magical number. I think it depends on what we see. But that's my mental note. If you ask me what is your mental number, somewhere between 4, 5, 6, 7 would be really good numbers. But again, I do emphasize there's not a magical number by which we want to disclose something, the data for that study. In terms of did you ask about the duration? Can you repeat your question on what you're asking on the duration front? No, sorry. Just in regards to your discussions with the FDA prior to filing, I think you mentioned duration would be one of the things that you'll be talking about since they don't have a particular mandate, but what are other items that you think are worthy of discussion prior to filing? Sure. So just to make sure that I clarify the question, the specific item that we would be asking the agency is duration of follow-up, another duration of response, the duration of response is the property of the product, but the duration of follow-up that they would like to see is typically a subject to discussion as part of a BLA dialogue. The BLA pre meeting typically has a component of logistics involved in it. It usually has a component of how you're going to build your BLA. BLA is a very large document, exactly where to find something. And then there's other components that we ask questions about. It's a bit of a logistic meeting as well as guideline for next steps. Sometimes the other topics, scientific topics also pop up. I won't go into too much detail. Obviously, that's something that's proprietary to each company as to what they discussed at the pre BLA meeting. Got it. And I guess just one final question from us is really the cadence of data, it seems like it will be primarily second half focused from kind of all the programs that are running. Are we thinking about that correctly? Would you release kind of top line data melanoma, then a filing and then kind of full data sometime in 2021? Is that how we should be thinking about it? Or is there a different cadence of results reporting the results? Right. I wouldn't rule out any specific patterns in any shape or form. Just specifically talking about melanoma top line data, the way I'm thinking about it right now is possibly just disclosing very high level top line data and then submission to FDA and maybe disclosing more information at a medical conference. That's sort of how we're thinking about it right now. Terrific. Well, thank you again and congrats on the progress. Thank you, Ben. Your next question comes from the regulatory path in melanoma and cervical cancer? Sure. Thanks, Madhu. We do have plans to initiate a broader dialogue with EMA Health Authorities called CHMP potentially in later part of 20 20. It's not that there has been no dialogue. We obviously have a number of clinical sites that are active in EU and as part of that we submit what is called a clinical trial authorization. So a CPA has been submitted and preliminary dialogue has been had with local health authorities. But we do intend on starting a sort of a more of a centralized procedure later part of the year in 2020. Okay. And just a more practical question about the PD-one combination studies. So you all give the TILs, do the IL-two treatment. And then is there like a washout period before you start PD-one? Like how much of a gap is there between the Till procedure and the beginning of PD-one administration and the combination studies? So the PD-one is administered prior to Till. And that information to the degree I can speak to is available on clinicaltrials dot gov. But it won't be able to go into details of the study design, Madhu. Okay, thanks. Sure. Your next question comes from the line of Biren Amin from Jefferies. Please ask your question. Yes. Hi, guys. Thanks for taking my questions. And it was great to see you earlier today. So Maria, with the melanoma cohort 4 fully enrolled, how do you think about the baseline characteristics of this cohort compared to cohort 2 in terms of median prior lines as well as in terms of PD-one refractory status? Thanks. Hi, Biren. Thank you for your question. We have not been analyzing Cohort 4. We actually have a data integrity document in place where we don't compile the data for cohort 4. So I won't be able to speak to the patient population in cohort 4. I did note that we designed the protocol the same way. The patient population definition is the same between Cohorts 24 and we tried to keep the participating sites to the degree we could control it the same. Okay. And then can you just talk a little bit about the PD-one selected Till? What are you hoping to gain from this program in terms of activity? And I guess what are you currently seeing in the head and neck cohort with Gen 2 that's allowed you to decide to move forward with not just the GEN-three, but the PD-one selected Till? Sure. So some of the data for PD-one selected Till was presented at I think it was 50, 2018. The criteria for that program was there was some preliminary data around T cells that ultimately recognize the tumor because they have seen the PD L1 of the tumor. So a Till that is expressing PD-one high, they recognize the tumor not only beyond what Till initially identified, but they have literally touched the tumor, the tumor cell. So that was the idea around the selection process. And again, there was literature showing that these are more potent TILs. They have better activity and cell killing capability. When we presented this at SITC in 2018, we showed in fact that the Till that are PD-one selected have enhanced autologous melanoma cell killing capability and it was quite remarkable. So we decided to move that product into clinic. In terms of what the bar would be, we have disclosed for GEN-two in a very, very preliminary set of data back maybe a couple of years ago now that median DOR was around 2 to 7 months for our head and neck patients. So we are looking to try and elongate the median DOR. That would be our goal for the additional cohorts. Got it. And then maybe just one last question, Maria, in terms of the landscape of TILs and how you think about neoantigens? Do you view this as a competitive approach or a complementary approach? Because it seems there are some pharma companies that are investing in this. And do you feel that some of these could potentially be synergistic to Till's? Thank you for that question. I think they may cover slightly different landscapes. In my opinion, when we have diseases that are high mutational load, such as possibly melanoma, we are thinking head and neck, lung, These are diseases that there is multiple targets and there needs to be multiple cells that would hit those targets. So the challenge with them would be identifying that specific neoantigen that a T cell could target. And if you don't have that, then it's really hard to hit them. So I do think that they would occupy different spaces. I think neoantigen targeted therapies could be beneficial for lower mutational load while Till are maybe more beneficial for higher mutational load. And this would last as long as we don't know exactly what targets you're trying to hit with various cell therapies. So yes, I guess I see them complementary maybe. So are there any pharma companies that you think complement those? I don't know if I can address that. There's a number of companies who are interested in that particular landscape and we of course monitor them very closely. Great. Thank you. Thank you, Biren. Your next question comes from the line of Joe Catanzaro from Piper Sandler. Your line is now open. Hey, guys. Just maybe one quick one for me. So Maria, you had mentioned that as part of your commercial preparation, clinical side engagement is a main area of focus. Now that Cohort 4 melanoma is closed, what are the opportunities from now until potential approval to continue to maintain and expand that clinical site engagement to the current ongoing studies allow you to do that? Would you potentially expect an expanded access program that would allow you to do that? How are you thinking about that? Yes, great. Thank you, Joe. As a matter of fact, that is something that is very much front of mind. This is why and Frederick commented about this. For the IOVACOM202 study, we are adding a cohort into that study that will enroll melanoma patients with the selected Till product, 145S1. That's exactly the purpose to allow access to Till products while we are bringing this the LN-one hundred and forty four like to lose to market. Okay, great. That's all I have. Thanks for taking my questions and congrats on the progress. Thank you so much, Joe. There are no further questions at this time. I will now turn the call over back to Maria for her closing remarks. Thank you, operator. Overall, I'm very pleased with the progress we have made and our prospects of becoming the leader in the Till development, manufacturing and commercialization. Indeed, in just 4 years, we have gone from our first patient in the clinic to preparing our first regulatory submission for approval. We have the potential to impact lives of thousands of patients with melanoma and cervical cancers who have exhausted current treatment options. Our work is possible, thanks to the valuable contribution of many individuals, including committed shareholders, hardworking employees, clinical investigators, collaboration partners and patients and patient families who motivate us. We look forward to realizing this shared vision for this product with the individuals that are in need of therapy. Thank you. This concludes the call today. You may now disconnect.