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

Hello, everyone, and welcome to our next session. My name is Asthika Goonewardene. We are thrilled to have the folks from Iovance with us on this installment of the Truist Securities Life Sciences Summit. From the company, we have Maria Fardis, President and CEO, joining us today. Maria, welcome. It's a pleasure to have you here, first time on our platform.

Thank you for the invite. Much appreciate the initiation of the coverage as well.

Yes. I might as well mention that. So we actually just freshly initiated coverage on Iovance with a buy just on Monday. We are definitely just about the deal space, and we'll talk about that more. Before we start, let me read out my disclosure, and I'm going to hand over to Maria to do some introductions to the company. So this call is arranged by Truist Securities Research for use by institutional investors and issuer clients as defined by FINRA. If you are not an institutional investor or issuer, please disconnect at this time. For required disclosures, please see our website at truistsecurities.com or our equity research library. Maria, I don't think people need a huge introduction to tell -- or Iovance, certainly, this has been a very hot company for a while. But what -- as it's the first time on our platform, why don't you maybe take a few minutes and walk us through what we need to know.

Absolutely, and thank you for that. So much appreciate the invitation. We will be making -- I will be making forward-looking statements. We're a public company. Just to remind ourselves, Iovance is a cell therapy company trying to treat solid tumor patients with tumor infiltrating lymphocyte, or TIL technology. We have a platform technology. We believe we have clinical data in multiple indications. I'll just briefly touch upon a couple of them. We have a consistent GMP manufacturing across multiple solid tumors. We are looking at next generation of products in our research programs. The pipeline includes metastatic melanoma and cervical programs that are pivotal as well as registration-directed programs in non-small cell and a head and neck program as part of the basket study. We are looking at combination of checkpoint inhibitors in earlier line of therapy for patients, as well as we do a lot of new indications through collaborations with partners such as NIH, MD Anderson, Moffitt or otherwise. They could be epidemic or otherwise. From a cash position, we closed our year last year at $635 million cash in hand. We have global rights and IP to our technology, and we're starting our Iovance manufacturing facility, which is called iCTC. Just to remind what the technology is about. This is a technology where we harvest the cells, the immune cells that have come for the site of a tumor, and we expand them ex vivo. We rejuvenate them and then we infuse them back into the patient. Now what is the concept? The concept is that in most healthy individuals, our immune system is able to -- it's very competent, is able to fight off any unhealthy cells that it sees, any oncolytic cells that it sees, and it removes them. In cases where the disease still prevails and becomes a metastatic disease, for example, either due to genetic factors, predispositions, for example, or environmental factors, the TIL still recognize the tumor, and it's called the tumor neoantigen and come to the site of tumor. And so that recognition component is what we are taking advantage of with TIL technology. And why is that is because what we have learned over the course of the year is that disease specifically such as melanoma, which is particularly high mutational load disease, have thousands of new antigens and identifying them or the key driver mutations has not been successful to date. So we collected TIL from the tumor itself from the patient, expand it ex vivo, provide it back to the patient. It's a onetime therapy, and it's very much individualized therapy. It's relying on the patient's own immune system. In terms of investment highlights. We have a large market opportunity that we are addressing. Again, solid tumors. We are looking into combinations in early-line. We have multiple indications that I talked about, mainly in solid tumor, although we do have a hematologic malignancy program as well. We are looking at being the first-in-class to come into the market, hopefully, for a metastatic melanoma cervical cancer. From a regulatory perspective, we have an RMAT designation for melanoma and a Breakthrough Designation for cervical. We have Orphan Drug and Fast Track for both indications. We have capacity for manufacturing in both U.S. and EU. And I've talked about our iCTC facility, which is under construction. And we have treated well over 400 patients at this point with Iovance products. In terms of what we accomplished in 2020 and where we're going in 2021. In 2020, we completed enrollment in our melanoma pivotal program. We continue our dialogue with FDA regarding a potency assay that is required to define our products in order to file our BLA. We completed our cervical cancer pivotal program as well in terms of patient dosing. We presented data for head and neck, where we combined TIL plus pembrolizumab in patients that are PD-1 naive. We also, through a collaboration with Moffitt Cancer Center, presented non-small cell lung cancer data, which was very exciting, and we are expanding in that indication. And we have moved our Gen 3 into clinic as well as maintained an over 90% manufacturing success rate in hundreds of patients. In 2021, our key focus area will remain on our potency assay. We have completed now additional cohorts of the cervical cancer program, specifically Cohort 2, which may also be part of the original BLA. We are expanding our non-small cell lung cancer program. We are also expanding our head and neck program. We have initiated a 16-day manufacturing product in the melanoma program, and our iCTC facility is now open and sort of open for business in terms of preparing for clinical manufacturing in late 2021. At a really high level, the data that we have presented in melanoma has been presented at AACR as a plenary session, and is expected to be presented as an oral session in ASCO. What we have shown is that the Cohort 2, which is our C-144-01 study, maintained a 36.4% response rate. This is in a highly pretreated patient population. There, 100% of them have received prior anti-PD-1, about 80% have received prior anti-CTLA-4. And as an average, they have 3.3 prior lines of therapy. The median duration of response was not reached at 28 months of study follow-up. And we noticed that the responses still continue to get deeper over time. And this is quite encouraging and remarkable in our opinion. I won't go in too much comparison between checkpoint, TCRs, CAR-T and TIL. TIL is -- maybe I'll just focus on this part of the graph. It's really targeting multiple tumor antigens. That's the strength of TIL, and that's a differentiator compared to CAR-Ts or TCRs. It is a onetime treatment, similar to a lot of other cell therapies currently available. We have data in melanoma, head and neck, cervical, and lung cancer. We are seeing -- the toxicities are expected. There are no unexpected off-tumor toxicities, and it is an autologous product currently as the way we're manufacturing it. The manufacturing process is shown here at a really high level. Patient journey is on top, tumor journey is in the bottom. The patient comes in, gets consented in a clinical setting. About a centimeter of the tumor is removed, and is shipped to our manufacturing facility. The patient then goes home. The manufacturing process that we are currently using and intend to take to the commercial landscape is a 22-day manufacturing process. At the end of the 22 days, we harvest the cells, wash them, place them in an infusion bag and certain media and we freeze it, and we are ready for infusion. When the patient is ready, they come back to the hospital. They start a lymphodepletion procedure, which is 7 days, 2 days of cyclophosphamide, 5 days of fludarabine, very similar to other cell therapies. They receive their TIL, followed by up to 6 doses of IL-2, which is expected to take about 2 to 3 days. And once the adverse events are resolved, the patient goes home. A picture of iCTC, our manufacturing facility, which is expected to start commercial manufacturing in 2022, is shown here. As I noted before, first set of clean rooms are complete. Clinical supply is planned for 2021 and commercial in 2022. Just a brief oversight in terms of our intellectual property. There's been a lot of questions and interest in this. We have a very broad IP landscape. TIL from various sources, including: tumor; marrow; peripheral blood; whether it's frozen or nonfrozen; remnant or digest are all claimed very heavily. The manufacturing process, maybe a 22-day, which is Gen 2; 16-day, which is Gen 3. Co-stimulants maybe used. Selection processes, genetic modifications have all been claimed. And then combination of TIL and various immune checkpoint inhibitors in clinic as well as the populations have all been claimed. I won't go into IL-2 variant, where we do have an IL-2 program that we have licensed from Novartis, and we continue developing that program. This is over 25 granted or allowed patents. They are on composition of matter as well as the method of manufacturing, and the manufacturing process have all been claimed. The sort of indications we are pursuing, as we talked, is very large. When we think about U.S., new cancer diagnosis annually is around 1.75-or-so million cases, unfortunately, get diagnosed. 90% of that is solid tumors. And the indications we are pursuing in melanoma, cervical, various lung and such populations or head and neck are particularly large, and the death rate remains quite high. In many of them, anti-PD-1s have made a significant improvement, yet the patients do progress on anti-PD-1s and still are in need of subsequent therapy. Our pipeline is shown here. The melanoma program has completed enrollment, so has the cervical and the pivotal cohorts. The head and neck study has also completed enrollment. Our basket study, which has a number of cohorts, including different indications is ongoing, and there will be data presentation of Cohort 1A, which is lifileucel plus pembrolizumab in patients that are PD-1 naive melanoma at ASCO 2021, along with the Cohort 2 continuation of data that is also presented at ASCO. We had previously presented data, the head and neck data, which is TIL plus pembrolizumab in patients that are PD-1 naive in head and neck at SITC. We continue with activation of sites for a new program that could be registration-directed and supported, LUN-202. And we continue enrollment in CLL-01 study with our PBL program. In terms of next-generation, we continue focusing on, as I noted, IL-2 analog. IOV-3001 is the product we have licensed from Novartis, and we continue with IND-enabling studies this year. We have looked into selecting more potent TILs, such as PD-1 positive TIL. We are looking into genetic modification methods, including PD-1 knockout, and we have talked about doing this through collaboration with Cellectis through a TALEN technology. And we certainly have optimized the process in shortening the manufacturing process, including Gen 3 or core biopsy. With that, let me stop and see if there is specific items that I can answer your questions with.

Of course, we have a bunch to dig into. So yes, first up, really appreciate the overview. That's super helpful. I think it would be also helpful press to hear from you what it took to get to the manufacturing process. Because in our previous conversations, we've talked about how manufacturing tends to be somewhat overlooked in cell therapy space, and it is probably a huge component of it. So maybe talk to us about that, why it took you to get to this Gen 3 22-day manufacturing process from what was originally like a 6-week long run out, nonstandardized kind of process that -- which is largely used by a lot of academic centers.

You're correct. It's an excellent question. And when we look back at the earlier days of the company, when I joined the company, a couple of things were -- are main considerations for me. The 6-week manufacturing process in an academic setting is doable because they're down the hall. They can do a bridging therapy for their patients. They don't have to have a supportive study for registration. So all of that is possible if you could do bridging therapy and you don't have to have a nice clean patient for regulatory purposes. However, the landscape of care has also changed. So back in 2011 or '12 when some of these academic institutions were treating patients mainly with TIL, the patients were PD-1 naive, and they were treatment-naive, many of them. So the patients had a little bit of time possibly to wait with maybe an IL-2 or chemotherapy administration as the bridging therapy. Today's patients or even back in 2016 when I joined, those patients are going to be post PD-1. These patients are progressing rapidly. And our intent was to target a regulatory path, which is a single-arm strategy. For a single-arm strategy, it's critical that there is no other bridging therapies that we assess the patients by RECIST 1.1, which means every assessment requires a confirmation of response. It's critical that the patients are not coming in, not having had progression on prior therapy. So there's a lot of requirements and criteria that needs to be in place for a registration-supporting study, rather than one that you would do possibly as a clinical study at an academic institution. What did that require? That required the manufacturing process not to be 6 or 7 weeks long. It also requires that it's completely consistent. The manufacturing process that today is 6 weeks and tomorrow is 7 weeks is not a GMP process, even if it is run in a GMP suite. One has to have a very clear set of SOPs as to what is getting done at every single day. It required an understanding of the process, Asthika. I think we -- I had spent a lot of time looking at the process with my team. We understood what exactly is being done at each step of the way, what exactly is the component of TIL that is important and what is maybe something that we can let go of. There were some in-processing steps which were historical from NCI. There were pauses in process, and those pauses where to phenotype the product, even though there's an association between TIL properties and the response. There wasn't any end, and this was well-publicized by NCI back between 2010, '11, '12 years. And so we were aware of that literature. So when we sort of thought about it, we realized that there's some in-process pauses that don't need to be there. They were there historically. They can be removed. And so that was our first goal: remove things that we are not really yielding to the product. Those are interesting steps scientifically, but not necessarily from a commercial perspective. Our initial intent was to keep the product profile very similar to NCI product. We subsequently proceeded to develop additional manufacturing methods, such as Gen 3, which is 16-day. And although the product profile is quite consistent, as a matter of fact, well, we started thinking, what is the shortest we can do with this product. Not just keeping everything consistent with NCI, but what is the shortest we can do. And we could go to 16-day manufacturing, and that is what we are rolling into metastatic melanoma now in our Cohort 1C of COM-202 program.

Got it. And just also -- so just with [indiscernible] as well, Maria, if you wanted to then adapt this 16-day manufacturing process across the board to all the other indications that you're looking for, what kind of -- what would you require to do? Let's say, you want to do the same cervical as well. What kind of data would you need to produce to adopt the 16-day process?

I think the first question for ourselves, is this a better product for these patients or is it not? If it's equivalent, then it really would be just a COGS reduction, not a clinical benefit. So I think the question we're still trying to resolve in our own heads is, are we offering a clinical benefit with the shorter manufacturing products or is this purely just a COGS reduction undertaking? And I think that depending on which -- what is the answer, we can decide, is this something you want to roll out to every single patient or do we think that Gen 2 is adequate? So I don't know if I can answer that, Asthika. I think that I really would love to see this Cohort 1 fee data on the patient population that is coming through before we can decide is this something we want to do or not. I guess my mental bar would be that it needs to be at least as good as Gen 2, otherwise there's no -- the COGS reduction is something we probably could do in Gen 2 anyway.

Right. Okay. Maria, there's a lot of focus on this year producing the pivotal data. And so maybe can you walk us through where you are right now? We've obviously seen some very encouraging signals from, let's say, in the melanoma. The Cohort 2 has got -- every time you update, it's got great. You're basically showing that you're continually prolonging the median duration of response in every look. You have a pivotal cohort there as well. You also have the pivotal cohort in cervical. What's the cadence of events that needs to happen for you to go in and then do that, the data cut, and to look at the pivotal data and then start the filings?

The key item still is our potency assay that we have been talking to FDA. We have, in fact, submitted -- so just to level set for everyone. So Iovance was planning on submitting the BLA in 2020. We had been providing a lot of data to FDA through the course of our development. We had been continuing to ask if additional questions will be sent from the agency, and we had a Type B meeting around late September, early October in 2020, during which the agency still issued additional questions. We proceeded to answer those questions. We also had a self-assigned action item to validate a second assay that had been provided to FDA sometime ago, but we wanted to make sure that we validate and provide that data to the agency. All of that has been done and all the data is sitting with the agency. So the next step, you really need to hear from the agency to make sure that this package of potency assay is appropriate. Then if it is, and the next steps are for melanoma to proceed with BLA readiness activities and preparation of submission. For cervical, the next step is we do need to meet with the agency. We haven't really met with them for sometime now. We have clinical questions that we need to ask them, including are they interested in Cohort 1 alone or Cohort 1 plus Cohort 2. The amount of follow-up, we haven't discussed that with the cervical review team. And then, of course, making sure that everything else is in place before submission, before cutting the data and submission of that data for the BLA. So the data cuts are really pivoted around timing of submission, and the timing of submission is pivoted around the evolution of the potency assay.

Got it. And Maria, just can you walk us through why is this become an issue right now with the agency? And what's been -- what are [ some of the issues ] and also what are the questions that the agency is looking to answer here?

Yes. So we have been discussing the potency assay for this product with the FDA for sometime. Recall TIL is a first-in-class product. And the differentiator is not only is high polyclonal by nature, but it's targeting many different targets, thousands of targets from what our data shows. And that's a unique differentiator for TIL versus the other cell therapies that has been -- come to market already. So how do we define a product that has this many targets, has been something that we have been thinking through with the agency? We continue answering questions with FDA, and we have been answering questions through the course of development, and we are hoping to be able to finish sort of that Q&A through the course of 2021 and go ahead with submission. But that's been the nature of it. How do we define this product to kind of make sure that there's a perspective? The products that we released are released based on a matrix of various assays. Potency is one of them. There's identity, there's total viable count, viability, and of course, sterility. And under each one of them, there is multiple assays that we present before we release the product. So the discussion is not new, but we really do need to put a bow on it before we decide, okay, we have defined the product completely adequately not only this generation, but if any future generations can be know how to define them. And now this is ready for commercialization. The discussion has been ongoing, and we want to make sure that there's agreement on the potency definition before we proceed the submission.

Got it. And so this is largely, I would say then, a bridge that the FDA has not crossed before that's why they're being cautious. And I would also maybe...

Entirely.

Since this will be the first one. They also want to make sure that whatever is done here is consistent, that is something that could be upheld to everyone. Could you maybe walk us through from what you can disclose, what are some of the different approaches to potency that you could take here? And maybe with some of the pushback the FDA gave on the original potency assays that you submitted. I think you had wave 1 and wave 2 so far. And wave 2 is [ ready for ] discussion.

Yes. So we have submitted assays that are based on, for example, a cytokine release that is after stimulation of TIL. This is when we think about what is the potency assay, it needs to be something that is mechanism-based type of an assay. It reflects what a TIL is supposed to do when it's alive and when it's healthy. So the assays that we're looking into, many of them are extremely well-documented in literature. Our KOLs and advisers agree that these are the best assays that define TIL. And there are many ways of thinking about it. We have tens of assays that we use in our research program. Not every research assay can become a commercial release assay. In order for a release assay to be in a commercial setting utilized broadly, the assays have to be very robust. They need to be short in duration. They need to be low cost. Ideally, everything should be available, all the raw materials about it should be available through GMP sources, and ideally should not have intellectual properties associated with other institutions, for example, just to make sure that this is nice and clean in terms of ownership from Iovance perspective. So a lot of consideration goes into thinking about what is a commercial potency assay? What is a commercial disease potency assay. When we think about -- going back to the other question you had, Asthika. When we think about what is it that the agency has been asking, maybe I can give a little bit of a flavor of the most recent questions that have been coming through from FDA. The last 2 sets of questions the agency was asking regarding the statistical method that we had used for a certain -- generation of a certain table as well as they were requesting a positive control line listing. And both of those were provided. So the nature of the dialogue is about the logistics of the assay not to undermine it in any way, just giving you the flavor of what was the most recent questions that was asked.

Got it. Okay. And I'll also ask this. The agency -- [ or confers ] -- the agency does see what the benefit of TILs are and the rationale to proving something like this. And I'm assuming that it's also in the best interest to do this as well. Is that a fair assessment to make, Maria?

It's a good question. I know FDA typically would attend a lot of scientific conferences, and they usually would keep very well up-to-date with what is sort of out in the landscape. I don't know given how busy CBER has been with so many cell and gene therapy products coming towards them as well as the fact that the resources are spread in support of the COVID program, whether that is something that they have been able to spend the time to take a look at. And we certainly have not met with them since around October timeframe. So you're correct. I don't know if I can speak on how much detailed information they do or do not have.

Got it. Okay. That's helpful. And then to reiterate, you still plan on making filings with that later this year. Hopefully, if everything pans out, that's the target, and that has not changed, right?

That's correct. That's correct.

Excellent. Let's talk a little bit about some of the other areas where we can use TILs. Obviously, the initial data we've seen in melanoma and cervical has been very compelling. Maybe also, let's look at the speed of enrollment as well. So right now, you are going to be presenting PD-1 naive -- in PD-1 naive melanoma up -- coming up at ASCO. You previously produced PD-1 -- data in PD-1 naive head and neck. I'm wondering if you could maybe talk just a little bit about the speed of enrollment of these -- both these cohorts. There seem to be sort of similar number of patients. And maybe talk to us about what are some of the differences when you're looking to take TIL into earlier lines of therapy.

Excellent questions. In general, and this is just my general drug development experience. When you go to earlier lines, it's not always as easy to enroll patients. In late-line patients, they are looking for clinical trials. Many of them have run out of their therapeutic options. Many of them are very well-connected to patient advocacy groups. So they come and find the clinical trials. In early lines, it's not common that the patients necessarily would go to clinical trials. There has to be a reason for them to consider clinical trials because, obviously, they have available therapies. And this is a general statement not just about Iovance, but in my past life, I always would see the same somewhat challenging landscape in your enrolling treatment-naive patients. In terms of our treatment-naive patients, not only there were challenges in getting into early-line patients, but also we have had really issues in accessing hospitals during the COVID landscape through the course of 2020 for a product that is administered in a hospital setting. So there was more than one challenge through the course of 2020, particularly in the U.S. as they were having issues with hospitals being very overwhelmed with COVID. Now as we see COVID sort of getting better resolved in the U.S., at least, we are really encouraged to see that enrollment is going back to sort of better days. It still is going to take a little bit of time. We heavily rely on EU for many of our programs. And again, it's not just Iovance. We have global programs. U.S., EU, Canada are where locations that we are running clinical trials. So as long as we are having issues with hospitals, challenges with enrollment probably will continue. And again, I see that across the companies. This is not an Iovance-specific challenge. A second layer that we see, for example, with a new indication such as non-small cell is we just haven't had relationship with non-small cell lung cancer patients in terms of sites that are treating these patients and TIL therapy. TIL therapy is very, very familiar with melanoma physicians not only because of Iovance, but also they have known about TIL from decades of publications. So I recall when we started even with melanoma, we were having challenges because a lot of people were either running their own programs or they were not familiar with us. So there's a degree of familiarity that needs to be established, and we are just in that same landscape in non-small cell that we were in melanoma 4 years ago and then head and neck around 2, 3 years ago and now with non-small cell. I don't think there is a particular difference between them. I think the combination of treatment-naive patients in the middle of COVID, trying to get them to come to hospital for clinical trials where they have alternative therapies that they can receive at their local institutions as well as the fact that many of them are potentially, they may or may not even know about many sites, they may not know about non-small cell lung cancer, has been a combination of what has led to a little bit of a slower-than-expected enrollment through the course of 2020. But I do think that 2021 is looking better already, certainly in the U.S.

Got it. Okay. And then in terms of next steps. So obviously, the head and neck and lung are 2 that you've outlined here. How should we think about the kind of data you need to generate to then start looking at the potentially pivotal studies? Already, I think the LUN-202 study, they have cohorts that could maybe as you produce some data then start stepping them up and making them into registrational. Can you walk us through -- let's start with lung and what those 2 cohorts are. And then what does that registrational cohort actually look like in terms of biomarker as well as number of patients, et cetera?

Excellent. Yes. So we use a rather similar strategy that -- in lung that we have used in melanoma and cervical, which is can we find a single-arm strategy with an unmet medical need patient population to get this product to potential approval? Definition of what would that patient population look like in non-small cell, we define the patients as patients who do not have an oncogene driver mutation. And then we divided them -- the 2 cohorts are based on TPS score of less than 1 or larger equal to one. And the reason we did that is statistically the way we designed LUN-202, each of the cohort is [ the same as to stage ] design. They can get expanded or they can get combined. If we see that the cohorts have very similar responses, we can combine them. So there's opportunities here to just take one of the subset and expand them or combine them and expand them. And all of these patients are unmet need. They're post chemo-immunotherapy patients, which is standard of care for them. And typically in second line, really available therapy for them would be docetaxel, which is about a 9% response rate. So that's how we're thinking about LUN-202 in terms of study design.

Would you also consider, Maria, and I'm also wondering if there's data to support specifically in, let's say, primary refractory patients, patients with primary refractory PD-1 because [ you set that goal. I understand there's quite ] an unmet need there as well, patients who just flow through those agents. Is that also something that you could also consider given that you also have a 21-day manufacturing process as well -- a 22-day manufacturing process as well?

Yes. Great question. Are you asking in light of lung? Or are you asking in light of any indication?

Actually, in any indication because, yes, the primaries are really coming out as their own group of patients who have their own specific needs.

I completely agree. And we presented our data for Cohort 2, I think it was SMR 2019 where we presented this data, and we broke down the patients that are primarily refractory versus not. We will provide additional data as part of ASCO as well. So this is absolutely something that I think we should think about in terms of how much time does the patient spend on their prior anti-PD-1. I agree with you. I entirely agree that that's an excellent patient population. Defining it is not always fairly easy particularly -- let's go back to lung for a second because the landscape is a bit more complex than it is in melanoma. The complexity is that there's chemotherapy on board. And so if it was purely just immunotherapy, the definition of primary refractory is a little bit easier. But since there's chemotherapy on board, now you have 2 different agents. And so we did try to define it that way, and this is precisely how we designed the cohort with that thought in mind. But it's not such a clean cutoff that we probably could do in melanoma. So we did think about it at that exact same way, and we thought that the best way of defining it is the way we defined course 1 and 2 in our LUN-202.

Got it. Okay. The last time is to be happy. I want to start talking about your commercial rollout. So obviously, it's very exciting that you have the filings this year, and I would -- given the Fast Track, the RMAT, the Breakthrough Therapy designations, all that. This whole point that once the potency assay is resolved, you'll have a very, hopefully, a very quick regulatory process. What are you going to prepare for this commercial rollout? Now you already built -- you've already built the commercial scale manufacturing, it's going to come online in, if I remember right, late 2021. So what do we do in terms of the building the sales force? What kind of a sales force would you need? How much overlap is there between, let's say, melanoma and cervical versus maybe some of the other indications?

Excellent question. So we started actually commercial readiness activities about a year ago now. We are being very prudent in building a commercial organization until we get clarity from FDA. However, we do have a small commercial team that has been very active. They're excellent. There's an extensive amount of prior cell therapy experience within our team. And they have been simply excellent in terms of focusing on really 3 main areas. One, it's site readiness. And the reason we focus on this is because we have seen the earlier cell therapy products when they came to market. And I've always said that it was a story of success, but they came to market so quickly that they did not have an opportunity to build the market, prepare the payers, prepare the hospitals extensively. Although now, things are looking a lot more promising. So we want to make sure that we have a lot of sites that are ready. We have a lot of relationships with them and we continue sort of expanding and building that as time allows. The second aspect that we have continued focusing on is the payer landscape. We continue our dialogue with the payers. We have engaged CMS extensively as well as the private payers. And we continue dialogue around sort of understanding the value that lifileucel may bring to the patients, particularly in light of the patient population we're treating. And then the third arm of the commercial readiness activities is what is called chain of identity and chain of custody, where we want to make sure that we support the patient and the hospital through the course of patient care and patient treatment. In terms of the manufacturing facility, you're correct, we are pretty much done with the core and shell of the facility. We have moved in. And what we are doing is we are starting our preparation activities for clinical manufacturing later part of this year and commercial in 2022. Our original plan was to launch with our partner, WuXi, which has been doing a lot of the clinical manufacturing for us, and that's still an opportunity and an option for us. We have not ruled out one or the other. We have multiple options in terms of commercialization, really depending on exactly when we reach the market. So there's a lot of different potential options here for us.

Got it. Excellent. One question I have to ask is on your cash position here. You obviously had such terrific raises in 2020, ended the year with $635 million in the bank. How should we think about capital allocation and R&D spend in 2021 and the next few years? And I'm also wondering, like what the strategy was with that size of a raise? Was it to actually see you through all the way to potential profitability? Or do you have something big expansion efforts, et cetera, that you need to invest in, in the near term?

I think those are all opportunities, Asthika. We will remain very opportunistic, but at the same time, very careful about our spend. We were thinking that it would be fantastic not to have to do a raise through the course of reaching commercial. I'm not necessarily saying profitability, but just reaching the commercial landscape. And so that was the sort of the rationale behind it. And we continue with that design of we would like to be in a position with a couple of years of cash on hand at any given time. And we would like to be opportunistic. If something surfaces, which is an excellent fit with the company, we would like to make sure that we have the opportunity to think about it and consider it. So it has allowed us to do that, which is very helpful.

Got it. Excellent. Great. This is great. We're at the top of the -- of our time allotment. It's been a pleasure to have you. And we thank you, you and the audience, for joining us today. I hope you have a great...

Thank you so much for your time. Thank you.

Bye-bye.