Welcome to the Iovance Biotherapeutics Virtual Key Opinion Leader Roundtable. My name is Latif, and I will be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. To ask a question at any time, please type your question into the Ask a Question box, then click Submit. Please note that this conference is being recorded. I will now turn the call over to Sara Pellegrino, Senior Vice President, Investor Relations and Corporate Communications at Iovance. Sara, you may begin.
Thank you, operator. Good afternoon, and thank you for joining us. Speaking on today's call, Dr. Brian Gastman, our Executive Vice President of Regulatory Affairs, will provide a brief summary about our TIL therapy, lifileucel, and moderate a discussion with our guest panelists, who are key opinion leaders in the field of melanoma and cell therapy. Then we will open the call for questions from the audience.
We encourage everyone with questions to take advantage of the time with the KOLs to learn more about their perspective on the melanoma treatment landscape and TIL therapy. Additional Iovance team members on today's call include Dr. Frederick Vogt, our Interim President and Chief Executive Officer, Jim Ziegler, our Executive Vice President, Commercial, Dr. Friedrich Graf Finckenstein, Chief Medical Officer, Jean-Marc Bellemin, Chief Financial Officer, and Dr. Raj Puri, our Executive Vice President, Regulatory Strategy and Translational Medicine.
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 and transactions, pre-commercial activities, clinical trials and results, regulatory interactions, plans and strategies, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interactions, licenses and collaborations, cash position and expense guidance, and future updates.
Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statements. With that, I will turn the call over to Brian Gastman.
Thank you, Sara, and good evening, everybody. Welcome. I'm a practicing surgeon who recently joined Iovance from the Cleveland Clinic, where I was the primary investigator and I led a multidisciplinary team in treating melanoma and specifically operationalizing several Iovance and other TIL clinical trials.
I'm very excited to be here tonight and to be at Iovance. Today, we have two prominent key opinion leaders who will address the unmet needs and current treatment practices for advanced melanoma patients, as well as perspectives on TIL therapy and preparations for lifileucel in general and within their treatment centers. Today's call is occurring on the heels of the FDA's acceptance of our biological license application, or BLA, for lifileucel for patients with advanced melanoma who have progressed on or after available standards of care.
Our BLA is under a priority FDA review with a PDUFA or Prescription Drug User Fee Act date of November 25th. As you can imagine, we are busy preparing and executing our pre-commercial and onboarding activities for a potential launch. Today, we're joined by, again, two prominent Key Opinion Leaders, including Dr. Mario Sznol. Mario, someone I've known for many years and is co-director of the Cancer Immunology Program at Yale School of Medicine.
He's had many leadership appointments, including as the past president of the Society for Immunotherapy of Cancer, and currently serves on the Iovance Scientific Advisory Board. His clinical experience with TIL therapy goes all the way back to his fellowship days in the 1990s with Dr. Steven Rosenberg at the Surgery Branch at the National Cancer Institute. In addition, we have Dr. Krishna Komanduri.
He serves as a Professor and Chief of the Division of Hematology and Oncology at the University of California, San Francisco, also known as UCSF. He's also had many leadership appointments, including as past president of ASTCT, and is currently the co-chair of the TIL Working Group, where he leads a multidisciplinary educational effort about TIL therapy for healthcare practitioners.
Krishna has established CAR T therapy units and cross-functional teams to deliver CAR T therapy and other cell therapies for cancer. Surgeons obviously also play a key role in TIL therapy, so as needed, I will chime in with my perspectives from time to time. Mario and Krishna, thank you so much for being here today. With that, I'm going to start with Mario for a few questions to set the stage on the current and emerging treatment landscape and unmet needs in advanced melanoma.
Mario, if you don't mind, can you tell us a little bit about your practice in terms specifically of the % of your patients who are untreated, that is, primarily treated, second line and beyond, patients?
Thanks, Brian, for the invitation. I don't have those exact numbers for you. We see, you know, a fair number of new patients per year with newly diagnosed metastatic melanoma. We also see quite a number of patients with stage two and stage three disease that we follow in our practice.
As you know, a large number of patients in the first-line setting are cured of their disease. About 50% are cured. The remainder then go on to second and third-line therapies. In fact, some of the patients, of those 50%, they're not all cured with the therapies. They may need a second treatment, such as surgery or radiation, to get them to that final state of no evidence of disease.
Thank you. When you consider how you will treat a new patient who's naive to all therapies, do you consider what the next level of therapy might be? In that paradigm, is PD-1 monotherapy, anti-PD-1 monotherapy, considered in your practice for the metastatic and/or non-resectable setting?
We rarely use anti-PD-1 alone anymore. We still like to use Ipilimumab and Nivolumab combinations, and we either use the dose ratio of 3 in 1 in many patients, sometimes 1 in 3, dose ratio, which, as you know, has almost the same activity with slightly lower toxicity. With the approval of Opdualag, which is a combination of relatlimab and Nivolumab, we can treat patients who we would have otherwise have given anti-PD-1 alone. Those are the patients who we think might not tolerate the toxicity of Ipilimumab and Nivolumab. The Opdualag only slightly adds to the toxicity of anti-PD-1.
We feel that those patients who we would have treated with anti-PD-1 alone before, we can give Opdualag with almost the same amount of safety and possibly almost the same efficacy as with the combination of ipilimumab and nivolumab. The question is, do we think about second-line therapies? Well, yes.
I mean, you know, there's always a possibility that patients won't respond to frontline therapies or will be resistant. In that case, we try and get molecular phenotyping for BRAF mutations to see if we might be able to treat them with BRAF/MEK inhibitors in the second-line setting.
Those who don't have BRAF mutations or KIT mutations, for example, there's really nothing standard of care at that point other than chemotherapy. We start thinking about clinical trials or other therapies for those patients, even in the frontline setting.
Take a patient then in the resectable setting that got post-operative anti-PD-1 monotherapy and then fails and is not further resectable, they're progressing distantly. What do you think should be the next step for those patients?
Right at the moment, we treat them with a combination of Ipilimumab and Nivolumab or Opdualag. Primarily, though, Ipilimumab and Nivolumab. We know that from a variety of studies, that, patients who progress on anti-PD-1 alone, if they receive the combination of Ipilimumab and Nivolumab, their response rates can be in the range of 20%-30%.
That still remains the frontline treatment for metastatic disease, even in patients who have progressed off anti-PD-1 in the adjuvant setting. As you know, quite a number of patients in the adjuvant setting receive BRAF/MEK inhibitors. Those patients also get Ipilimumab/Nivolumab when they recur.
Right. You already alluded to my next question, which is really when you would begin Ipi/Nivo. Given that you've already described when you would do that in your treatment sequence, what would you consider next, though, for a patient, regardless of BRAF status, if they're, if they failed Ipi/Nivo? Would you consider, for example, intratumoral therapy like T-VEC, which is FDA approved, or some other combination or clinical trial?
You know, we prefer immune therapies prior to anything else. Even if they have a BRAF mutation, if they don't need, you know, immediate, tumor bulk reduction, we would like to offer them some sort of immune therapy in the second-line setting. There's all sorts of different flavors, though, of patients who progress off ipilimumab/nivolumab.
There's, as I said, a subset of patients that, progress after responding for a while. Those can be reinduced with ipilimumab and nivolumab. There's a number of patients who have oligometastatic disease, so one or two sites of disease. Those patients can be treated with surgery or radiation. The patients who have multi-site progression, we would either offer a clinical trial or in some cases, we might try, at this point, Opdualag, after progression off Ipi/Nivo.
The response rate to Opdualag in the second-line setting isn't very high. It's only in the range of around 10% or 15%. We really don't have a lot of options. If they don't have a BRAF mutation and they have multi-site progression after ipilimumab/nivolumab, we really don't have a lot of options.
Including, would you include T-VEC in that answer?
You know, I apologize for not answering that question directly. We very rarely use intratumoral therapies at our institution. We use them selectively for patients who have single sites of disease or limited regional disease. We don't use T-VEC if patients have disseminated metastatic disease, because the chances of response in that setting to an intratumoral therapy is very low. We would prefer to offer them a clinical trial rather than going with T-VEC in that setting.
We've really talked about the standard care options for these patients. Can you just, in your own words, I know you brought this up, but really, what is the biggest unmet need for these patients once they hit that barrier?
I mean, it's in the metastatic disease setting, if you have multi-site progression after Ipilimumab, Nivolumab, or Opdualag, and you don't have a BRAF mutation, there's a huge unmet need. If you do have a BRAF mutation, very few of those patients are cured. In fact, we've looked at our own data, only about 10% of patients.
Well, 20% of patients who have long-term survival with BRAF/MEK inhibitors, and about half of those may be able to come off therapy. Most patients who get BRAF MEK inhibitors in the second-line setting will progress through therapy, and we really don't have anything for those patients either. Those are two huge unmet needs in our field. Actually, TIL could address either one of those settings.
So, uh-
There's one more unmet need, Brian. Let me just interrupt.
Okay, please.
There's a group of patients that could respond to ipilimumab and nivolumab again. Those who have responded, then progressed while they're getting nivolumab or who've gone off therapy and then had progression, but they had major toxicity from the immune checkpoint inhibitors. That's another unmet need because often you can't go back to the immune checkpoint inhibitors in those patients, even though they might be responsive.
Collectively, these groups of patients that really are out of these options, you would call them in terms of their risk, in your own words, you would call that risk of death, you would just want to hear from you say, like, how high that risk is.
very, very high. You know, I'd be if you have multi-site progression in those settings, the chances that we can cure your disease is close to 0 at this point with standard of care therapies.
segues into the next segment of our questions, which is the fact that your institution and you in particular, are well recognized for clinical trials and their accrual. When do you recommend the trials, even over our current standards of care?
It depends on the setting. Are you talking about the first-line setting or the second-line setting?
Any. you know, there's obviously clinical trials, but let's maybe for this purposes, let's talk about 2nd-line setting or beyond. Where you still have standard care options, potentially for those patients.
If you've had a doublet, immune therapy, immune checkpoint inhibitor therapy, and you have multi-site disease progression, so you can't treat them with radiation or surgery, you don't have a BRAF mutation, we would prefer a clinical trial at this point because there is no standard of care.
If you have a BRAF mutation, we would probably still offer a clinical trial as long as those individual patients don't need an immediate response. In other words, if we have a window that we think that we can offer them a trial before we give them the BRAF MEK inhibitors, we will offer a trial in that setting.
For patients who do get BRAF MEK inhibitors, there's a real problem because once they start progressing on BRAF MEK inhibitors, it's very hard to get them off the drug. Some of those patients will progress more rapidly when you take them off the BRAF MEK inhibitors. In that setting, having something that works very quickly or something that you can add to the BRAF MEK inhibitors would really be preferred. There are very few trials in that setting among our institutions.
Thank you. Assuming lifileucel is approved later this year as the first TIL therapy, how do you plan to use it within the standards of care paradigm? Maybe more specifically on top of that, how does your center plan to have TIL, in this case, lifileucel, available, and will that impact considerations for clinical trials, in that setting, given what we just discussed?
you know, that's a complex question because, you know, The bottom line is, we are preparing to have TIL available here as soon as possible. As you know, Dr. Kluger, my colleague, was one of the major accruers to the trial, so we have a lot of experience giving TIL. We even did a small study of our own.
We think that TIL would be very important in certain subsets of patients. For example, one group that I think could really benefit from this therapy are the ones who have had toxicity from immune checkpoint inhibitors, and we would offer them the immune checkpoint inhibitors again, but we can't because of toxicity. Those patients, I think, would be great candidates for TILs.
I think patients who have progressed off ipilimumab, nivolumab, and are wild type for BRAF, I think we certainly would consider TIL, perhaps ahead of clinical trials, or maybe after a clinical trial, but in those settings. For patients who have had immune checkpoint inhibitors and BRAF MEK inhibitors and are progressing, I think TIL would be a great therapy for those patients, even ahead of a trial.
The reason for that is, as I said, it's very hard to get those patients off BRAF MEK inhibitors, and you need something that would work relatively quickly, and I think TIL would fit that bill. For now, that's the way I think we would start incorporating TIL into our practice. When we had a TIL trial open here before, we had numerous referrals for patients in those categories.
You and I have discussed this before. Do you, in that regard, can you comment on, checkpoint inhibitor recycling? Does that, would that be effective, do you think, in this setting?
Yes. I mean, we only reintroduce immune checkpoint inhibitors when we think the individual has a chance to receive benefit. As I said, there's a couple of those groups. One is the people who have responded really well, have gone off treatment, have been off treatment for a while. Those patients, you would certainly offer immune checkpoint inhibitors again, because they can have great responses.
Even patients who have responded to double immune checkpoints and are being maintained on nivolumab alone, those patients can be reinduced with immune checkpoint inhibitors again. Some of them can't receive it again because they had grade three or four toxicity at the beginning. If you have TIL available for that group of patients, you would probably offer TIL ahead of the immune checkpoint inhibitors.
Did I make that clear?
Yeah. No, that was, that was terrific. Last question in this little segment is: what's your impression of the level of awareness and interest in TIL therapy, like lifileucel, maybe in particular? For those who do know about it, what's the feedback and impressions you're getting from referring physicians and patients?
Well, at least in the academic community, as you know, it's very well known. At centers that treat a lot of melanoma patients, the data with TIL are known, and I think people would be very excited and interested to have that as a therapy to offer.
For community physicians who are not as aware about TIL therapy, it really doesn't matter because they would refer those patients to an academic center for a trial or for any available standard of care that they don't have. Even if the community physicians aren't aware of TIL therapy, we would be aware of it when they refer to us for treatment in the second or third-line setting.
I want to thank you very much, Mario. I'm That was a very informative discussion, and I'm going to turn this over now to Dr. Krishna Komanduri. Now that we've covered the landscape of melanoma care, let's learn more about the preparation and coordination among cell therapists around lifileucel as a new and unique opportunity for them, excuse me, as cell therapists in solid tumors. As a experienced cell therapist yourself, who also has experience in the TIL space, how does your knowledge of lifileucel and its data impact your enthusiasm for this form of cell therapy?
Thank you, Brian. I am very excited. I'm not a melanoma doctor like Dr. Sznol and others, but as somebody who has been active as a hematologist and transplant cell therapist, the data look very interesting. It looks like for a subset of individuals, there are excellent response rates, and I think that the other thing that was impressive to me about the data was that a subset of the responders really seem to have long duration of response, which is really encouraging with respect to the potential for long-term impacts.
For somebody who has been, as a laboratory-based scientist in the T cell immunology community for a long time, and as somebody who, at the time of my training, thought about the prospects of immunotherapy and saw TIL therapies, including in the Rosenberg group, obviously, that you and Mario know well, advance but never get to the clinical arena, this is really, I think, an important milestone for all of us. I'm hopeful not only for the direct benefits that will come from lifileucel, but also what this means with respect to a transition to a better future.
Fantastic. Along the question I asked Mario a few minutes ago, what is the level of awareness among your colleagues in cell therapy, and what is the TIL Working Group to do to educate the broader community of cell therapists?
There are challenges, I think, in cell therapies broadly. If you look at CD19 CAR T therapies, not enough individuals who should be getting them are getting them. I think if you look at individuals like me who live in advanced academic centers, and I've been in multiple academic centers over the last 20 years, we are pretty savvy, and we have often participated in these trials, and we know it's coming, and we're hoping, obviously, for approvals and the ability to use these patients in the non-clinical trial, use these therapies in the non-clinical trial setting.
We recognize also that there are broader challenges, and that one of the things that has led to underutilization of CD19 and other CAR T therapies, in the hematologic malignancy setting, is that people need to be educated.
The TIL Working Group is a not affiliated group that includes individuals like me who have transplant and cell therapy backgrounds, individuals who primarily manage melanoma, including medical oncologists and surgeons.
We have been meeting together with support from Iovance, we now plan to distribute that support over other companies, including individuals that are developing other TIL therapies, to really come together and say, "What are the things that people need to understand about these therapies, including the potential clinical benefits, but also what are all the infrastructural challenges?" The goal is to learn, I think, from our lessons.
Early on, we did have a CAR T working group, but it was as these therapies came on, a lot of individuals needed to know more than they did because they weren't involved in the early clinical trials. We're trying to, I think, broaden understanding of the continuity of care and the coordination required so that when these therapies become approved, there will be broad uptake, and many individuals will learn from the experiences of others.
Just to probe a little deeper, to qualify what you just said, would you then say that the lessons learned from CAR T are being applied here so that some of the little potholes aren't stepped in this time around? Is that? Do you want to elaborate on that?
Yeah, I think so. There are obviously, as Dr. Sznol noted, many patients are managed in the community. They may be referred to an academic center, and then they may be referred if they have, a therapy that requires cellular therapy to a separate physician who might specialize in cellular therapy.
There are places for communication along that spectrum, and ultimately, we want patients to be empowered as well. There certainly have been lessons learned, you know, initially, when CAR T therapies came online, there was obviously only one product and then two, and now we have, you know, a large number of products approaching 10 products in the CAR T therapy space now that are approved.
TIL therapies and other therapies for solid tumors are now being added to our, you know, immunotherapy armamentarium. There are unique aspects of TIL therapy, but there are also a lot of broad lessons, and we definitely want to learn from those lessons, and then also, obviously, focus on the things that make TIL therapy unique from the other therapies that we're doing.
Great. Well, you obviously are a leader in your institution. Could you describe how your cell therapy unit is coordinating with solid tumor oncologists and surgeons who prepare UCSF for lifileucel, and maybe even comment on the similarities or dissimilarities to working with other liquid tumor oncologists for CAR T therapy?
Every cancer that we treat is managed somewhat differently. The individuals who manage lymphoma are often different than the individuals who manage myeloma, for example. As Dr. Sznol noted, there are people in the community who may be managing patients who refer directly to a cell therapy unit, or in some cases, patients are referred when they have relapse or progression, or managed by a second academic physician who might be one of our colleagues, and then referred to us for cellular therapy.
Some of those issues will also occur here. There may be a melanoma doctor in the community who refers to an academic individual. In our case, at UCSF, we have one united division of hematology and oncology, and we also do transplantation and cellular immunotherapy within that division.
We have really excellent cross-talk between the doctors who treat melanoma primarily and individuals who do transplantation, cellular therapy in other places. That's, you know, they may be more separate and might work in related but collaborating divisions. There are unique things.
Obviously, TIL therapies are derived from T cells that are in the cancer, and that brings into play, obviously, surgeons like you. You know, but normally we're collaborating. Many medical oncology specialties involve close coordination between medical oncologists, surgical oncologists, radiation oncologists, and others who are involved in multidisciplinary care. I think the concept of multidisciplinary care and the need for integration is not unique to us.
Again, the roadmap of many patients with lymphoma or who need an allogeneic transplant for acute myeloid leukemia or get treated with, you know, for myeloma, is that they may have 2 or 3 different doctors involved.
These are not things that we are, you know, surprised by. There are some unique, obviously, aspects of coordination that related to TIL therapy, and you have to educate in some cases, a separate group of individuals who may not have interacted with us before. Again, these are principles that we think about often and are ready to tackle as we bring, you know, necessary therapies to patients who need them.
Great. you know, we've listened to a number of sites, that tell us that inpatient capacity is not a rate-limiting issue. can you describe UCSF and satisfying patient demand for TIL therapy?
I would say that broadly, we do worry about capacity issues and that, you know, we're doing a lot to address them. I wouldn't say it's not an issue because hospitals tend to run very efficiently, and we, you know, when we have therapies, you know, we apply them to all patients who need them.
Right now, there are a lot of therapies coming online. I wouldn't say TIL therapy is necessarily stressing the equation, but the fact that we have gone from, again, 1 to 8 approved CAR T therapies, and we have more on the way, as well as other T-cell therapies, not only TILs from Iovance, but hopefully TILs from other companies down the road, and transgenic and other T-cell therapies.
All of us are thinking, I think, very actively, and consciously about growing capacity, and addressing that. That's not unique. When autologous transplant became the appropriate therapy for lymphoma and myeloma, we had to rapidly scale infrastructure. Allogeneic transplantation from donors to cure diseases has, you know, become safer in older individuals and much safer in individuals who didn't have registry donors, and that's led to massive expansion.
In Miami, when I moved to Miami, we grew an allogeneic transplant program 10-fold in a 10-year period. We're used to thinking about scaling. I wouldn't say that resources aren't limiting, but we are used to also when therapies become appropriate for patients, and that, you know, we recognize that we have to develop and scale the infrastructure.
The one thing about TIL therapy is that we are not using apheresis because the cells are not collected from the peripheral blood as they are for most other CAR T therapies, where the patient has to have a T cell collection. Here, the cells are coming from a different place, that is, from the operating room.
There are certain aspects of the spectrum of care, for example, apheresis beds, that aren't going to be taxed. On the other hand, obviously, there is an inpatient stay that's required. I would say at UCSF, you know, we actually have an amazing hospital that will open in 2030, and the plans for that are on the UCSF website, and we're very excited about it.
Our growth in oncology, and we expect oncology growth across the board, and certainly in hematology and cell therapies, is something that we're actively planning for, and we're working on ways to expand cellular therapy, you know, in our cellular therapy laboratory, our apheresis and inpatient capacity quite broadly. We're not particularly concerned that this is uniquely going to stress our systems, we are obviously working on all aspects of this, you know, almost all the time.
Along those lines, with the potential approval of lifileucel, as early as, you know, in this calendar year, would that cause an immediate need or an extensive expansion for existing resources, including staffing, partners for yourselves, infusion chairs, and patient capacity? Especially, you know, especially since you mentioned all the different CAR T approvals.
Yeah, again, I would say, to say this in a slightly different way, that we're not particularly concerned about the demands, that lifileucel alone will somehow stress us beyond any point. We recognize that continuing growth will need an expansion in all of these approaches, and it's not just because of lifileucel, but because of novel CAR T therapies across the spectrum.
At UCSF, we actually have a Living Therapeutics initiative, which is a broad campus-wide initiative academically to develop CAR T therapies, to develop other novel T-cell therapies, and to develop other living cell therapies for a broad range of human diseases. We have actually brought online preclinical and manufacturing capacity, and we're thinking very consciously about all of these elements.
We know that cellular therapies, including this one, are increasingly going to be deployed for a broad range of conditions, and we're doing everything we can. Our goal is obviously not to stay behind, where we need to be in terms of capacity. It's always a challenge, but we're really working on these issues.
Well, thank you. Very comprehensive answers so far. In fact, you've actually allowed me to move a little faster to my last question. That is, how do you envision the handoff with a real-life patient when it's going to go from a medical oncologist to a surgical oncologist, possible perioperative issues, then to manufacturing, and ultimately into your, you know, lymphodepletion chair, and then ultimately, TIL therapy and how do you plan on managing that communication and handoff from one group to another so it seems to be seamless?
These aren't easy things, but I've had the privilege and difficult role of coordinating many of these things in the context of stem cell transplantation and then CAR T trials and CAR T therapies when they came online. These are things that we do in a very thoughtful way. In the stem cell transplant community, we actually even created accreditation groups like the Foundation for Accreditation of Cellular Therapy.
The reality is, when we do all of these things, we not only expect quality control and processes to exist, but for there to be standard operating procedures that really govern the principles for all of this, and all of this is then externally accredited and actually reviewed by payers as well as the Foundation for Accreditation for Cell Therapy.
We know that all of this stuff, we have to have internal procedures that are consistent with national standards. It really requires on communication, and that you have to have a framework and a blueprint for doing it. I would say these are things that are exist. I've served as a medical director of what's called a GMP lab or a good manufacturing process lab.
You know, we have contingencies and processes, you know, if we get a call that a product's manufacturing is delayed or there's a contamination in a collection for something that's going to be infused back into the patient, we know what to do, and we have processes in place. This is, you know, there are new challenges here because of the coordination with surgery.
I think, as I alluded to before, and as Dr. Sznol said as well, the role of multiple academic physicians who work together is not unique to TIL therapy. It's something that also exists in an autologous transplant patient or an allogeneic transplant patient, and indeed exists for most CAR T processes.
We're used to doing all of the things that are required, including, you know, chain of custody from the product as it moves from our center to a manufacturing facility and back, and then the important amount of crosstalk that governs all of these handoffs. This is really part of our culture.
I would say we have a very special cell therapy universe, and we're excited about, I think, what we've been able to do in the past. There are definitely some new individuals and who we'll be interacting with, but all of us recognize that this is one of the first therapies for solid tumors and that we're going to have many more solid tumor-based T-cell therapies, whether they be CAR T cells or transgenics or TILs.
We also know that other companies are developing TIL therapies and that this is something that we have to get right. We're all working very hard on all of this stuff, and again, that's part of what we're doing in the TIL Working Group, is try to share best practices, and approaches so that people can approach this and be as successful as they can early, and then, if there are any early, bottlenecks or mistakes, to learn from those in an iterative way, I think improve that process as quickly as possible.
Fantastic. Thank you so much. Before we open the call for questions, I wanted to hear from Mario and Krishna about a couple of bigger picture items. Both of you have involved with TIL therapy over the last several years. Dr. Sznol, as a former fellow of Steven Rosenberg at NCI, how do you feel now watching the process of lifileucel go through FDA review, hopefully toward an approval?
Brian, just to correct, I wasn't actually a fellow in the Surgery Branch, although I worked with Dr. Rosenberg very closely for, you know, 12 years, first as a being a monitor at CTEP for the protocols that came through, and then I worked actually as an attending on the immunotherapy service for a couple of years with him.
I was sort of there at the NCI when TIL therapy was being developed. I saw the, you know, the responses, the progression of therapies over time. Actually, one of the first things I did when I left the NCI was one of the leaders of the immunotherapy subgroup of the IDSC.
This is a part of CTEP that was responsible for overseeing development, therapies of development of new therapies. I actually commissioned a paper on TIL therapy back around 2005 and 2006 because I was so excited about it, I wanted to see it developed. To go from there 17 years ago, to see it, you know, nearly approved is really exciting.
I was always a big believer that cell therapies would play a major role in our treatment paradigm, and I see it coming true today. I guess the very short answer to that is having watched it from the very beginning, it's really exciting to see it, you know, nearly come to market at this point. That's TIL, and, you know, obviously, the other therapies that are already there, is amazing.
Your correction of my question only made it more poignant. Thank you. That is a good answer. Dr. Komanduri, as past president of the ASTCT and current co-chair of the TIL Working Group, how are organizations and fellow physicians thinking about TIL therapy on a broader level? You know, 'cause you're really at the highest echelons of those thinking about it from a operational standpoint nationally. I'd love to hear from you about what's going on.
I'll just add before answering that question that, you know, when I went to UCSF as a heme/onc fellow and as a laboratory trainee at the Gladstone Institutes of Virology and Immunology, you know, I actually did research in HIV immunology because there was no cancer immunology, amazingly, at UCSF.
Returning, you know, roughly 25 years after when I was there as a fellow and seeing a robust, you know, active program, both nationally with multiple approved products and an amazing pipeline at UCSF, you know, it's really exciting for me. This is like we've been waiting for this for a long time, and, you know, this and other therapies are really giving us a brand new world.
I was, actually, you know, privileged to be president of the ASTCT in the year when CAR T therapies became approved. I was one of the individuals who led internal thought processes. We used to be called the American Society for Blood and Marrow Transplantation, but a lot of us had been working in T-cell immunology, and many key individuals in the, what was called the ASBMT, had developed some of the earliest CAR T and TIL therapies.
We actually revamped the society and, you know, changed the name to the American Society for Transplantation and Cellular Therapy to better reflect this brave new world. You know, we worked early on, not only I think in the CAR T space, you know, scientifically and clinically, but also to work with Medicare.
I met with the chief medical officer of the Center for Medicare and Medicaid Innovation. We met with payers to develop a framework. We developed the coding systems that we use to bill so that physicians actually get reimbursed and worked on inpatient and outpatient payment models. Obviously, as I told you know, ASTCT is one of the two co-parents with the International Society for Cellular Therapy.
For FACT, helped, you know, really to develop some of the frameworks for accreditation. I actually happened to sit on the FACT board of directors at that time when FACT was thinking about how it can develop standards to make these therapies safe. I'm really excited. You know, I was recently also chaired the ASTCT Cellular Therapy Committee.
I'm still on that committee now, and we're working really on all of these things. You know, how do we educate people about the infrastructural challenges? How do we ensure that patients have access? There are still, sadly, unfortunately, some, you know, disparities that patients face for complex therapies.
How do we make sure we have adequate payment models? And also, obviously, how do we facilitate research, both preclinical research as well as clinical research, and make sure that we're funded to do all of this stuff? I would say we are working very hard, and Dr. Sznol and others, obviously, in SITC, and I've had, you know, the opportunity to serve in leadership positions at the American Society of Hematology and others.
You know, I think that there's really a broad multidisciplinary effort, and we also recognize that, you know, that many of the infrastructures have been more narrowly focused, for example, on hematologic malignancies, and that we kind of have to think, as we've talked about multiple times, you know, forge new alliances and broad coalitions and make sure that we have the multidisciplinary support that's required. I think we're all doing this very actively because we want these therapies, if and when they get approved, to, you know, be, accessible, safe, and scaled, to the broadest possible population.
Aside from TIL therapy, are there other emerging technologies that either of you think are going to be joining the space in the near term, let's say the next 12 months, certainly in the post-PD-1 setting? Along those lines, assuming the lifileucel is approved this year, would you think that they now have a different threshold to break in order to achieve approval themselves?
Brian, could you repeat the last part of that question?
Yeah. Yeah. If there is something that you're excited about, will the approval, if, assuming it happens this year, of lifileucel affect at what the threshold it would be for the next therapy to come in for those who are PD-1 fail?
That's a, also a difficult question, right? Because you're asking, well, will it lower or raise the threshold for new therapies to come in? Generally, when a new therapy like this is approved, it probably lowers the threshold for things to come in. Right, it establishes a precedence, but what those trial designs will need to look like in the future, it, to me, isn't clear.
I haven't completely thought about that yet. I think, though, there will be a lot of excitement once this product is approved, and there are a lot of questions that remain to be answered. I mean, you, TIL is, to some degree, a first-generation product. There are going to be improved ways of supporting the cells once you give them back.
We need to work on maybe reducing the amount of lymphodepletion that's needed for these cell therapies. There's probably improved methods for culturing the cells and for generating the best cells for therapy.
There are genetic modifications that we might provide to these cells over time. It's almost infinite, the number of things that you can think about that could go from where we are now to even better outcomes in the future. You know, I guess that's a long way of answering the question, but I just think there's so many investigational things that we can do to make things even better, and it'll build on the TIL therapy in many different ways.
Brian, I, that was, of course, an extraordinary answer, so I don't want to try to duplicate what Mario just stated. I think, I do think in a sense, you know, this breakthrough, if it happens and we have an accessible therapy, a commercial therapy for patients, is really a wonderful milestone.
I do think that, I'm happy that that Iovance is continuing development and that there are other therapies, other companies that are working in the TIL space. At UCSF, there are a lot of really exciting things happening in the CAR space, in solid tumors, you know, where we, of course, don't have any approvals, and individuals working on ways that T cells can, you know, succeed in inhospitable environments, like where the tumor microenvironment actively suppresses the T cell response.
I do think we're going to see more exciting approaches, including sequence therapies, more modified therapies, you know, combinations of T cells and NK cells and other things. I do think that this is a milestone. It's a great milestone. If it happens for Iovance, it'll be fantastic. I think that, you know, again, this is just an evidence of that the immunotherapy world, and the, in particular, the T cell immunotherapy world, is, you know, going to see more rapid evolution in the next 5 to 10 years. I would predict not in the next 12 months.
I don't expect other broad T cell therapies for solid tumors, but I think in the next 5 years, 10 years, we're gonna have many more tools at our disposal across a broader range of malignancies. We're also gonna see the TILs, like Iovance, the TILs, and others, be applied to other diseases besides melanoma. I think that that's also very likely.
Well, you know, I'm glad you brought those points up because one of the things I've noticed, if you could even have seen it at ASCO, where we presented our data on altering how we expand TIL, you probably know that we have already a TALEN PD-1 knockout TIL product in clinical trials.
I think that those points are not being wasted on us at all. In fact, I don't believe there was a point that you made that we aren't already thinking about or currently working on more specifically. It's a very exciting and fast-moving field indeed.
Just very quickly, want to just, you know, last seconds before we open this up, you know, assuming, again, that we, you know, we hope and pray, it will get it approved, that we have an approval.
You know, from a patient perspective, maybe Mario, since you treat melanoma patients, but if you want to chime in, Krishna, is there how do you feel about the landscape and perspectives from a patient therapeutic options that the patients now will have with the addition of, a potential addition of lifileucel to their armamentarium?
I think the way to look at this, Brian, is that, we all want to cure 100% of our patients. You know, we've been very fortunate in melanoma and kidney cancer and some other diseases, and melanoma in particular, where we feel like for patients who might meet eligibility criteria for a trial, for example, their chances of, living 5 years is better than 50%, and many of those patients who are alive at 5 years are going to be cured. What we're ultimately trying to do is move up that cure rate slowly over time, right? It's not going to be, you know, 25% at a time, 35% at a time.
If in absolute terms, if we can move up that cure rate, 5%, 10%, 15% with each new therapy, we're really making progress. I actually think, too, we'll bump up that cure rate. I can't tell you exactly what that number is, but I think from both a physician and a patient perspective, it's great, right? We will be able to cure more people with these types of therapies. you know, I don't know what more to say. I just think it's a wonderful development.
I completely agree with Mario. I don't think he could have said it better, and I don't think I can add anything to that very hopeful comment.
Well, those are all my questions for today. Let's hear from our investor relations team about questions from the audience. I believe, I'll let, Sara, you, take those.
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Thank you all.
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