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

Fabulous. Thank you. Okay. It's fantastic. I will give you a brief update in terms of what our progress has been in 2020, and then we will go through some of the data, including the head and neck data that we have released at SITC today. In the past quarter, we have announced that our last patient in Cohort 1 of cervical cancer program was dosed. In head and neck, we are releasing some data in a combination with KEYTRUDA, an anti-PD-1 therapy, in patients that are naive in Pap therapeutic setting. We have started our LUN-202 clinical program as we had promised that we will start the program by year-end. We continue having excellent manufacturing success rate of over 90%. And now we have dosed over 400 patients in our Iovance-sponsored program. We have had our Type B meeting held with the agency, and we have released data that we continue working on our potency assay to assure that there's alignment with FDA in acceptance of what potency assay would define TIL products. We also have noted that we have data for 6 months from initial response by IRC that will be accessible by FDA as a BLA submission support and then Cohort 2 can be supportive. Just to remind ourselves what TIL are, a tumor-infiltrating lymphocyte is basically a form of our immune system. We are resecting the tumor that has been created at a -- for a -- in a cancer patients. We are expanding these cells that are coming from the tumor outside of human body. And once we have billions of cells, we are returning those cells back to the patients. The cells are rejuvenated and expanded into numbers. They also are -- as I noted, they're basically our immune system. In a normal healthy individual, these immune system cells come to the site of a tumor, and they launch an attack when a tumor is detected in our body. And most of us that are healthy, those immune cells ultimately remove the tumor, and they're able to eradicate the disease, which is why most of us are not walking around with metastatic melanoma. But in cases where the disease continues, due to either genetic predisposition or environmental factors, those -- the cells -- the immune cells all came to the site of tumor, and they recognize the tumor and they launched an attack. But either because of the pressure of the tumor being very high or because of the fact that are the TILs are being defeated by the tumor itself, they're not able to completely eradicate the tumor. So the hypothesis around this came from Dr. Rosenberg's lab in 1988, when he noticed that some tumors can spontaneously resolve in metastatic melanoma. And the idea was to expand that these tumors outside of human body and infuse them back into the patient. This is a highly personalized therapy. It's completely individually dependent. It's called autologous, and it depends on our own immune system and expansion and rejuvenation of those cells outside of human body. The process as shown on this slide, I'm showing you, the patient flow is shown on the top of the graph and the tumor flow is shown in the bottom. On the top of the graph, which you can see is the patient comes in, in a clinical setting. They're identified. Every section is taking place to take about 1 centimeter or so of the tumor. And that tumor is then shipped to our manufacturing facility. The tumor can be excised from skin, lymph nodes, liver, lung, various other tissues. And once the patient has recovered from surgery, the patient is released and they go home. So that's the 2 on the top. The tumor is then shipped to our manufacturing facility, where it's fragmented, it's placed in media and the cells that are in the tumor, depart the tumor and they start expanding. Over the course of a 22-day manufacturing process, we are able to expand the cells to multiple billions. At the end of the 22 days, we wash watch the cells. We put them in an infusion bag and we cryopreserve them, and Iovance is ready for infusion. Once the patient and the hospital is ready, the patient comes back in. So now we are on Step 3, on the top of the graph. The patient is going to a lymphodepletion regimen of 7 days of cyclophosphamide fludarabine. And once that lymphodepletion regimen is completed, we infuse the patient with their TIL, and we follow by up to 6 doses of IL-2 infusion. And once all the adverse events are dissolved, the patients -- they're dismissed, they go home, and this is a onetime treatment. So there's no additional follow-up, except for data collection. In terms of mechanism of action, once the product is infused, it's circulating in the human body, inside the blood, it recognizes the chemokines that are released from the tumor, it migrates from the circulation toward the tumor bed, and it binds through the TCR from the TIL to what's called the MHC of the tumor, through a tumor antigen recognition. And once this recognition takes place, the Step 3, the lysis process begins, the TIL start releasing Interferon-gamma, granzyme B, perforin, all of which support the killing that ultimately the TILs do on the tumor cell. From a time line perspective, Iovance has been around for a number of years. We took a license technology from Dr. Steve Rosenberg's lab in 2011. In 2015, an orphan drug designation was filed for the product. And in 2016, we started patient dosing. To carry on with our melanoma program, we started our patient dosing and we continued optimization of the manufacturing process through 2016 and 2017. In 2017, we assured this Gen 2 proprietary method that I just showed you is, in fact, leading to responses in patients, and we switched all of our manufacturing method to this proprietary Gen 2 method. We also started the dialogue with FDA in 2018 to understand what their requirements for a registration program would be. And they agreed that a single cohort in our existing study could be supportive of registration. As part of this dialogue, we also received an RMAT designation in melanoma, and we had received a Fast Track designation as well as orphan designation in melanoma from the agency, from FDA previously. In 2019, we dosed our first patient in our pivotal program, Cohort 4. And in late 2019, we actually closed enrollment and built our last patient into the pivotal program in January of 2020. We have presented data from our Cohort 2, which we have long-term follow-up at ASCO 2020. And I'll go over that data today with you. And we have now started a discussion with FDA about adequacy of what would support registration of lifileucel in melanoma. We also have additional indications that we have initiated and are following through. We started our cervical cancer program in around 2017. We have continued the dialogue with FDA to assure that a cervical supportive -- registration supportive program can be defined. And the agency had agreed that the existing study could be supportive of registration. Since then, we have expanded our cervical cancer program to multiple cohorts. Cohort 1 has been the registrational program as we have been planning it, and we have completed those things patients into the Cohort 1 in cervical program in third quarter 2020 as well. As part of discussions with FDA for cervical cancer, we have received an orphan drug designation as well as a fast track and breakthrough designation also. We have continued our data presentation for cervical cancer, and we have presented data at SITC -- at ASCO actually 2019. I'll go over that data with you today also. On the next slide, I will show you sort of the high level melanoma data. The key highlights are shown here. In 2019, we showed that the overall response rate in Cohort 2 and melanoma program was 36.4%, as assessed by investigators. We also had read our data by IRC, and that response rate was 34.8%. We were very pleased to see the concordance between investigator and IRC data. In 2020, at a high level, we have noted that the median duration of response has not been reached at 18.7 months of study follow-up. And again, I'll go through some of that data that we presented at ASCO. In terms of investment highlights, just to highlight where we are and what we are pursuing. We have a very large market opportunity, a very strong unmet medical need. Patient population that we are pursuing. We are initially focusing on checkpoints refractory patient. Patients who have received checkpoint therapy. And they've progressed on these therapies in melanoma. In cervical cancer, we're also sort of now exploring the patient population. We have a number of different company-sponsored programs that we are pursuing in different indications, including melanoma, cervical, head and neck, non-small cell as well as CLL. We have the potential to be the first cell therapy to be approved in solid tumors, melanoma and cervical cancers. We have been discussing with the agency in terms of our registrational path and our BLA for melanoma is now expected in 2021. In terms of efficiency of scalable manufacturing process, we have both U.S. and EU capacity through our CMOs. And where Iovance is building its own manufacturing facility, 136,000 square feet -- foot facility in Philadelphia. Our Gen 2 manufacturing process has been quite efficient with a 22-day manufacturing process. It is heavily protected by intellectual property from Iovance, and it has over 90% success rates really over the course of a few years. We use collaborations with academic institutions, heavily in start of new indications. We work very closely with, for example, NCI, where the idea originally came from Moffitt Cancer Center, MD Anderson, Yale and other institutions in developing new indications. And in fact, our work with -- the collaboration with Moffitt led to the expansion of non-small cell lung cancer indication by Iovance. I have touched upon some of the aspects of TIL therapy. It is a highly individualized specific and potent attack against the cancer. It is a polyclonal product in the sense that it targets a number of different neoantigens. It's quite effective in terms of targeting heterogeneous solid tumor cell types. The data in melanoma, cervical and head and neck and lung cancer has been provided previously. And TIL in each patients is specific and private to the patients, and we have published that the CDR3 signature for the TIL is quite individualized in both melanoma and cervical cancer. We do see persistence of the cells over the course of day 42 and sometimes beyond. And again, we have published that data as noted in the presentation. And we see that this limiting drug. It ultimately had immunological memory and is able to reexpand once its exposed to the antigen again one more time. In terms of comparison of TIL and CAR-T, TIL is also onetime treatment. Similar to CAR-T products, they target multiple tumor antigens, while CAR-T products has been mainly focused on targeting a single tumor antigen. The data is in solid tumors, mostly, and CAR-T product data is mostly in hematologic malignancy. The safety profile seems to be differentiated for TIL versus CAR-T, reminding ourselves that TIL is not genetically modified while CAR-Ts are. Our intellectual property is sort of very broadly built. We now have 20 granted or allowed U.S. patents. And these are for composition as well as method of treatments in various cancer settings. We claim a number of different technologies, including peripheral blood lymphocytes or marrow-infiltrating lymphocytes as well as various methods of manufacturing, use of various costimulatory agents as well as for populations that of the patients from a clinical perspective, that can use TIL. Our manufacturing picture is on Slide 13. It's called Iovance Cell Therapy Center, or ICTC. This manufacturing facility is out in Navy Yard in Philadelphia. And as I noted, it is 136,000 square foot facility. A very large facility for cell therapy, in general. We have, in fact, just about completed our clean rooms, and we expect to be able to move in by late this year in 2020. Our Commercial GMP manufacturing is expected to commence in 2022. We have put on Slide 14, the patient populations that we are pursuing. Just to remind ourselves from a market size perspective, a large number of patients, 1.6 million cases every year are diagnosed just in U.S. with cancer. Of them 90%, are solid tumors. And a breakdown of a few of the indications that we are pursuing is shown on the right-hand side of the slide. Of course, melanoma, cervical and lung are among very large populations that we are pursuing. And then head and neck as well as other indications that we are interested in are noted in this slide. Unfortunately, you noticed that not only the new cases is quite high, but we still have a large number of deaths annually. And again, this is the U.S. side due to progression on these diseases despite the fact that number of different other therapies have been approved today. Our pipelines slide is shown with -- on this slide. We are looking at melanoma, cervical, head and neck. We also have a basket study IOV-COM-202. I will briefly touch upon that. And we have now initiated our IOV-LUN-202, which is a non-small cell lung cancer registration-directed study as well as our CLL program. The bottom portion of this slide is showing the studies that we are doing in collaboration with MD Anderson, it's just a select view of the collaborative programs that we have. Now moving into metastatic melanoma program. Specifically, the patients still annually on a number of case -- new cases that are being diagnosed, 309,000 cases are worldwide diagnosed. And in U.S., it's 100,000 cases of melanoma. And in fact, this is on the rise. The number of deaths in global setting is 52,000 and the deaths in U.S. have been 7,000 fairly steady in the past couple of years. Available care for these patients, typically in front line is immunotherapy. Typically physicians start treatment with anti-PD-1. It may be as a single agent or in combination with anti-CTLA-4. If the patient has the BRAF/MEK mutation, they start with a BRAF targeted therapy or they may start with immunotherapy and then move the patients to BRAF/MEK. But once the patients progress on immunotherapy and/or BRAF/MEK, they really are considered unmet need, and their only option is chemotherapy with a response rate of around 4% to 10%. The OS of these patients per literature is around 7 to 8 months. So the patients don't have a very good, unfortunately, less expected once they progress, they progress on immunotherapy as well as targeted therapy. Our C-144-01 study was a Phase II study. The patient population is shown on the left-hand side, and we have 4 cohorts in the study. Cohort 1 was using Gen 1 manufacturing method that Iovance has developed earlier on. Gen 2 manufacturing is used in Cohorts 2 and 4. The patient population for Cohorts 2 and 4 are the same and the manufacturing product, which is the Gen 2 product, is the same as well. Cohort 4 is the pivotal cohort, and Cohort 2 was a supportive cohort that was started back in 2018. We have produced the data for Cohort 2 over different presentations, and I will now review the data that was presented at ASCO 2020 with you today. I will just highlight a few characteristics of the patients. The patient population, as an average, has around 55 years of age. They have received -- a 100% of them have received anti-PD-1 therapy, 80% of them have received anti-CTLA-4 therapy, and 23% have received BRAF/MEK treatment. As an average, they have received 3.3 lines of private therapies. And I think this is important to think about the way we count private therapies. If there's any therapeutic is giving concomitantly, that's considered 1 line. So if a patient received anti-PD-1 and anti-CTLA-4 at the same time, that's called 1 line for us. Almost all patients had progressed -- not only had received, but they have progressed in anti-PD-1 and anti-CTLA-4. We probably should pay attention to the LDH level of the patients, about 40% of the patients have elevated LDH. This is a poor -- marker for poor survival, unfortunately, as the patients have elevated LDH, they don't have very good life expectancy. From a disease burden perspective, the patients have around 106 centimeters. So think about a great fruit size of target lesions. This is not all the lesions they have, this is just a target lesion. And in terms of how metastatic the disease was, about 80% of the patients had over 3 lesions. So fairly metastatic patient population, with the bulky disease at baseline, is how we would describe our patient population. Treatment-emergent adverse events as well as adverse events over time is shown on this slide. If you look at adverse events over time, you can see the signature to a onetime treatment, bulk of the adverse event or on the left-hand side. And many of them has been resolved by the time the patient goes home by around day 10 to 14 or so. And on the right-hand side, we're showing the treatment-emergent adverse events that are over 30%. Many of these are quite common to what we expect to see with chemotherapy and IL-2. And again, in a single-arm setting, every treatment of our adverse events, of course, is produced. In terms of efficacy, 66 patients were evaluable for response. Actually, they were dosed. So all the 66 patients those are shown here. 24 of them had a response. So that transits a 36.4% response rate. 2 patients had a complete response of 3% and 33% of the patients had a PR. I think it maybe noteworthy to highlight also the percent of patients who had a stable disease. So approximately 44% had a stable disease. And why this is important is, recall our patients were all in progression before they enrolled into the cohort. So a stable disease is a clinically beneficial outcome for these patients as well. So not only the response rate is 36%, but the disease control rate is noteworthy at 80% as well. We have noted that median durational response has not been reached at 18.7 months of study follow-up. In terms of number of TILs that is infused, we see around 27 billion TILs that are infused and 5.5 billion as an average IL-2 doses has been given to the patient that's a median IL-2 administration doses. On the swim lane, what we are showing is time to response and you can see a number of patients actually have a response fairly early in their treatment paradigm. But the response can get deeper over time. They can turn from a PR to a CR. And what you can see on the left-hand side of this graph is the patient's prior response under prior anti-PD-1 or anti-CTLA-4 therapy. And what is noteworthy is many of our responders were, in fact, progressors on their prior anti-PD-1 therapeutics. And what this means is that even if a patient doesn't have really highly immunogenic disease, which they would have expected to have some degree of response on their anti-PD-1, they certainly could benefit from TIL therapy. So 79% of the responders had received prior anti-PDL-ipilimumab, and you can see that those patients, they have been responders or nonresponders on prior anti-CTLA-4 therapy. The waterfall is shown on this slide. And what you can see is the depth of the response is quite nice and deep. And in fact, if you compare over time, the depth of response deepened, the stars are showing patients who had a BRAF mutation. And you can see that the BRAF mutation is not a predictor of a response or master of in terms of TIL therapy. So 81% of the patients had a reduction in tumor burden, as you can see on this graph. We conduct a sensitivity analysis to see whether specific markers may predict the response. And it appears that at least for the factors that we considered prior use of anti-CTLA-4, BRAF mutational status, PDL-1 status that they don't seem to be a major drivers of response of TIL therapy. It appears that basically patients may have come from across the wider age range. They may have been anti-CTLA-4 or BRAF treated patients. And regardless of that, the patients may respond to TIL therapy. In continuation of the subgroup analysis, we also looked at LDH. We looked at some of diameters of target lesions at baseline. We looked at whether patients with liver lesions, maybe responders and/or liver or brain. And we are pleased to see the patients regardless of the location of the tumor may still be responders on this type of therapy. Our conclusion was that for heavily pretreated patient population, metastatic melanoma population with high disease burden at baseline, we still see a 36.4% response rate and 80% disease control rate and a median DOR that has not been reached at 18.7 months of steady follow-up. The competitive landscape is shown on this slide. There's a number of other agents that are being developed for post PD-1 melanoma patients, and some are in a combination setting and some are in single agent setting. And again, we can compare quite favorably with the responses we are seeing to date for our therapy. Moving into cervical cancer. What we can see -- sorry about that. We can see that this is still a very prominent disease, particularly worldwide. 600,000 cases are diagnosed annually for cervical cancer. And unfortunately, about half of these patients die on an annual basis. In U.S., we have better statistics. We have 14,000 patients that are diagnosed and 4,000 patients are dying. The standard of care has been changing in this patient population. It used to be just chemotherapy as a front line therapy. Now KEYTRUDA has accelerated approval in post chemotherapy with an overall response rate of 14% for the patients. And available care basically for the patients in post-chemo landscape, a second-line metastatic cervical cancer patient, is somewhere between 4% and 13% response. Our C-145-04 study, the Phase II study, that we are conducting cervical cancer, is shown on this slide. We have 5 cohorts at the moment. Cohort 1 is the pivotal cohort at the moment. And Cohort 2 is proposed PD -- anti-PD-1 therapeutics, which we are enrolling patients up to 24 patients in that cohort. Cohort 3 is in combination of TIL plus pembrolizumab in patients that are pembro naive or anti-PD-1 naive. Cohorts 4 and 5 are for pretreated or retreatment of the patients and patients that were treated with other agents such as our Gen 1 manufacturing. We have fast track designation and breakthrough designation, as I noted. And this data was presented that I'll show to you that was presented at ASCO in 2019. In terms of our patient demographics, on the right-hand side, you can see the mean number of prior therapies was 2.4%. 100% of the patients have received platinum therapy, 96% had received taxane. So they're all chemo exposed, of course. In terms of the bulky disease at baseline, the patients had 61 millimeters of disease as summary of target diameters. So again think about an orange sort of just target lesions at baseline. Histologically, they are about equally distributed between squamous cell carcinoma and adenocarcinoma. And in terms of how metastatic the patients were, about 60% of the patients had more than 3 lesion. So a fairly advanced patient population as well as in terms of bulky disease at baseline as well as a number of lesions that are detected at baseline. This product, as I noted before, has a fast track and breakthrough designation for cervical cancer. Adverse events profile is quite consistent, very similar to what we showed you in melanoma. On the right-hand side, again, we are showing adverse events over time. Again, very consistent with a onetime treatment. You can see the adverse events are mainly on the left-hand side. By the time the patient leaves the hospital, they are mostly resolved and back to baseline. And on the left-hand side, we are showing you treatment emergent adverse events. And again, quite consistent with what you have seen previously in case of metastatic melanoma. The response rate in the 27 patients who we had read for ASCO was 44%. 12 responders have been detected at the time, 3 of which were complete responses and 9 of them were partial responders. The disease control rate, again, remember that these patients are in progression coming into this study, was 85% quite remarkable at the time and median duration of response has not been reached at a median study follow-up of 7.4 months at the time. Again, consistent with our melanoma program, we were seeing TIL being infused at 28 billion cells, and the median number of IL-2 administered was 6 doses. A swim lane showed fairly similar signature between cervical and metastatic melanoma, patients see a response early, although the response can get deeper. And as I noted before, 7 months of median study follow-up, we still had 10 out of 12 patients continuing on study. The waterfall shows, again, the depth of response is quite nice and deep. The CRs are shown on the right-hand side, and the PRs are shown, to the left of that, the assessments were made by with this 1.1. The competitive landscape is actually getting more crowded for cervical. I think that a lot of drug developers are recognizing the need in cervical cancer. And so I'm delighted to see that there's other potential therapy that's coming into market for cervical cancer. We still remain quite excited about potential of TIL in cervical cancer patient population. We are looking at head and neck as well. We have a poster at SITC. I'm going to speed up a little bit. The patient population is shown here. There's actually a large patient population globally being diagnosed with head and neck cancers. In U.S., 65,000 patients get diagnosed and 15,000 patients unfortunately die. The available care in frontline, per NCCN guideline, remains immunotherapy -- chemoimmunotherapy as well as chemotherapy. In immunotherapy in frontline, one would expect around the 16% response rate and a 22 months of median duration of response. In chemoimmunotherapy, 36% response rate has been noted with 6.7 months of median duration of response. And chemotherapy, the most commonly used one called EXTREME, offers a 36% response rate and a 5.6 months of durational response. And second-line for NCCN guideline, one can offer anti-PD-1 therapy, and expected response rate is around 16%, with about 8 months median duration of response for this patient population. We had offered head and neck as part of a basket study, which has multiple cohorts. The specific cohort that has head and neck is Cohort 2A. This is TIL plus pembrolizumab being offered to patients who are PD-1 or PDL-1 naive. They might have received prior chemotherapy. And in fact, 89% of our patients did receive prior chemotherapy as well. And again, the poster is being presented at SITC. I think, on Wednesday, the poster is released online today, though. On the poster, we show additional data on efficacy, where we are showing the depth of response on the patients that responded. We had 4 patients who were responders, out of 8 who are evaluable. 9 patients are totally reported, 8 of them were evaluable. One patient has a CR and 3 other patients had PRs. And the swim lane also shows that, again, we have nice long follow-up for one of the patients at 15 months. That patient was a PR and the response deepened over time to a CR. 3 other patients, 1 of them has had a second assessment, and in fact, is a confirmed PR, but the patient has withdrawn consent. One had a PR and progressed at month 6 and unfortunately passed away. And a third one continues in response TIL, which makes the median duration of response not reached. Of the 4 patients, 3 of them had a CPS score of equal or over 20%, and 1 of them had a CPS score of less than 20% but over 1. And again, this is a patient population, which is more difficult to treat. This yields an overall response rate of 44% and a disease control rate of 89%. In non-small cell lung cancer, the data from a collaboration with Moffitt Cancer Center was presented at AACR. So this data is from that collaboration. They had presented 12 patients who were evaluable. Of the 12 patients, 3 of them had shown a response. 2 were complete response and 1 was a partial response. Of note, one of those responders, the CR with an EGFR mutation, post their TKI therapy, which is an encouraging patient population as far as unmet medical need is concerned. Median duration of response has not been reached. And the CR, at the time of the presentation, were all ongoing. The PR, I believe, had progressed at the time. The waterfall shows the depth of response as well as the responder as well as a few unconfirmed partial responses at the time of AACR as shown on the waterfall. On the right-hand side, you're looking at the swim lane and the CRs are highlighted and the PR patients, I believe, was patient 16, which had progressed at around 9 to 18 would still remained in study. As a result of this data as well as the fact that we have an in-house program and interest in non-small cell lung cancer, we have initiated a study called IOV-LUN-202. This is a Phase II study with a registration-directed intent. We have -- we believe we have de-risked the study designed by having 2 cohorts, one is TPS score less than 1%, and one is TPS score over 1%. Each of them 40 patients and each of them can get expanded, they're 2 stage, they can get expanded if necessary beyond 40 patients as well or statistically, we have designed the study in a way that if the responses are similar between cohort 1 and 2, we can combine them. Cohort 3 is designed for patients who are not able to do -- cannot do an excisional biopsy, so they're not able to give us about 1 centimeter of their tumor, and we are going to use core biopsy with a Gen 3 manufacturing for 15 patients. And Cohort 4 is basically a retreatment that we allow for all of our patients in case they participated in our clinical studies and they wanted to be treated again. Primary endpoint, of course, is designed as ORR by IRC; and secondly, our additional efficacy and safety endpoints. In terms of our research focus, we continue being interested in expanding the TIL platform with novel analogs of IL-2, such as IOV-3001. This is a product that we have licensed in from Novartis, and we had committed to start off our IND-enabling work in 2021, and we are on target. We continue considering selecting more potent TIL. We have developed a product for PD-1 selected TIL, and we have introduced that in clinic in our head and neck program. That study C-145-03 was not on the slide today. We started patient dosing with this selected TIL early part of 2020. We are interested in genetic modification, of course, to make TIL more potent. We have a collaboration with Cellectis on their TALEN technology to generate such products. And we certainly continue thinking about process optimization, such as our Gen 3 product, which is a 16-day manufacturing process and now thinking about how to make TIL therapy more sort of easier to administer, and we are using a core biopsy process that we're introducing in our LUN-202 study. From a footprint perspective, we have our corporate headquarters at San Carlos, California. It's about 20 minutes south of San Francisco and Bay Area. We have over 200 employees. Our other offices are in New York, Philadelphia and Tampa. In Tampa, we have our research team. And in Philadelphia, we have a team already started, including our manufacturing staff at our manufacturing facility, as I noted earlier, will be in Florida and Navy Yard. We also have a business office of subsidiary in Switzerland as well, given that our program includes a number of different sites in EU. From a financial perspective, we have 146.6 million common outstanding shares. We anticipate closing the year with a cash balance of over $630 million. And we just announced as part of our quarter end that in third quarter, we were at $719.7 million cash in hand. From a 2020 and 2021 goal, we had initially set a series of goals, including exclusive enrollment for Cohort 4 in metastatic melanoma, which was accomplished. We wanted to present our data, updated data,, at ASCO, and that was the data I shared with you in melanoma. We're hoping to share some of our early data in Cohort 4, and we did as part of the financing in May. We actually gave a highlight of top line data of a portion of the patients that we had. We expected to dose our last patient in cervical cancer in the pivotal cohort, and we just accomplished that in Q3. We are looking forward to discussing the TIL plus KEYTRUDA data in the head and neck indication at SITC, and our next steps are still continuing to remain very focused in resolving our potency assay issues with FAD to assure for submission of the BLA in 2021 and then also initiating our non-small cell lung cancer registration supporting study. With that, I thank you for your time. And if there's a few questions, I'm happy to answer those questions.

Thank you, Maria. We really appreciate the presentation. If anyone has any questions in the presentation, I guess, just send them to me. But I do have a few in my e-mail and box for you, Maria. So in addition to the head and neck highlights, kind of what are your thoughts behind the lung cancer strategy, specifically looking at the trial design in the 3 specific patient cohorts?

Yes. So we consider the patient population very carefully. Our strategy, in general, was to consider an unmet medical need patient population and yet as early as aligned as possible. We do know that when patients are late lined, it's very difficult to address them with immunotherapies, they're not particularly amenable to being treated and their immune system turning around entirely. So that was our general strategy. When we thought about the patients in non-small cell, there's really 3 different categories of patients, biomarker-driven patients, and of course, they're quite on unmet medical need. However, they do have a second line therapeutic option post their TKI. They can receive doublet chemotherapy with bevacizumab or including atezolizumab as well. So that patient population would be caught for TIL in third line. But patients that are PD-1 -- PDL-1 expression low or PDL-1 expression of 1 to 49 or even above that are certainly post their chemoimmunotherapy. They are unmet medical need. So we thought about that patient population very carefully. We chose second line post chemoimmunotherapy, yet we didn't want these patients to be very late lined. That's how we thought about it.

Excellent. And just a follow-up there, kind of looking at the data that you press released today that's going to represent today at SITC or -- can you into put context what this opportunity could be combining your TIL with a PD-1? And how that could potentially transform the treatment of head and neck cancer?

That's an excellent question. Thank you. There's a couple of ways of thinking about opportunities in head and neck. In front line, as I noted on this slide, there's -- certain chemoimmunotherapy can be a standard of care. EXTREME still is used as a frontline therapy and a single checkpoint in use. A single checkpoint in frontline would give a response rate of around 16%, chemoimmunotherapy would be as high as around 36%. So there remains opportunities in frontline, certainly. And one could transform that landscape to, for example, TIL plus KEYTRUDA. The second opportunity to consider is a directly outpatient population on the poster, which are post chemotherapy. The patients that we have in SITC poster are post-chemo. 89% of them have received chemotherapy. In second line -- so they're second-line patients. In second-line anti-PD-1 alone, KEYTRUDA itself would offer about a 16% response rate. So post chemotherapy with TIL plus KEYTRUDA at 44% response rate, we are highly encouraged with what we see. This is early data, of course. And so we look forward to having longer follow-up. For this particular poster, we had over 8 months of median study follow-up and median DOR had not been reached. But again, longer follow-up and additional patients would be really nice to see before we decide exactly how to position the product.

Excellent. Well, with that, we are hitting time. So I really appreciate you joining us today. I know it's not the same as being in person in Scottsdale, or seeing each other in the hall in San Francisco, but I'm looking forward to doing that, hopefully in the near future. And thank you again, Maria. And of course, Sara, from the IR team, we really appreciate you joining us today. With that, bye now. Thank you.

Thank you.