Status Update

Aug 17, 2021

Slides

or good afternoon, everyone. Giving the platform a moment for everyone to join. I see the number is getting higher right now. Okay. So I'm going to kick it off now that we have a lot of people. I'm Allison Soss from KCSA Strategic Communications, and I would like to welcome you all to the Stellus Investor Symposium on GPS. Before we begin, I would like to remind you that Stellus will be making statements on today's call relating to future expectations regarding the further development of and regulatory plans for GPS. These statements constitute forward looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995 and by their nature involve estimates, projections, goals, forecasts and assumptions and are subject to risks and uncertainties, which include, without limitation, risks and uncertainties associated with the COVID-nineteen pandemic and its impact on the company's clinical plans, risks and uncertainties associated with immunotherapy product development and clinical success thereof. The uncertainty of regulatory approval and other risks and uncertainties affecting Cellus and its development programs that could cause actual results or the outcomes to differ materially from those expressed in the forward looking statements. These forward looking statements speak only as of the date of this conference call and should not be relied upon as predictions of future events. While Cellos may elect to update these forward looking statements at some point in the future, the company disclaims any obligation to do so even if the company's views change. Additional information about the material factors and assumptions forming the basis of the forward looking statements and risk factors could be found under the caption Risk Factors in the Cellist Annual Report on Form 10 ks filed on March 23, 2021, and in other SEC filings. The focus of today's symposium is Cellus and Suite Clinical Program, GPS. So Doctor. Angelo Sturgio, the company's President and Chief Executive Officer, will begin today's program with remarks around today's event and then introduce our 2 additional speakers, Doctor. Yair Levy of Baylor University Medical Center and Doctor. Jagan Suski of Bellas. Following the presentation, we will hold a Q and A session with all of today's speakers. Please submit your questions at any time during today's program using the Q and A prompt in the webinar. We will hold all questions until the dedicated Q and A section where the team will answer as many as they can in the time permitted. We kindly ask you that your questions be addressed only to the subject of GPS, the subject of today's call. So with that, I would like to turn the call over to Angelo Sergio. Thank you, Alison, and hello, everyone, and welcome to Sellas' investor symposium on our lead asset, Gluten Peppers on GPS. First, I want to thank you for the participation and support in joining today's virtual symposium. We are very excited to take this time to focus on GPS to further discuss our clinical program, including additional details on our recently released data as well as the significant unmet need in acute minor leukemia or AML, the indication being studied in our GPS Phase III renal study. It is my pleasure to introduce our 2 expert speakers today, Doctor. Yair Levy and Doctor. Braden Ciesich. Doctor. Yair Levy is the Director of Hematologic Malignancies at the Baylor University Medical Center specializing in lymphoma, myeloma and leukemia among other hematological malignancies and focus on novel research endeavors. We're grateful that he has agreed to join us today to provide insight on the current landscape of AML, available treatment modalities and the challenges and opportunities faced. Mr. Levy is an expert in the space, and we're also pleased that he's a member of our Regal study steering committee. Following Doctor. Levy, we'll hear from Celeste's Doctor. Dragon Cesar, our Senior Vice President, Clinical Development. There's really no better person than Dragon to provide a deep dive into our science and greater clarity on our recent promising data readouts. Before I turn it over to those exceptional gentlemen, I'd like to quickly touch upon why we are hosting the symposium on GPS now. At Cellars, we believe that GPS has the potential to change the phase of treatment for leukemia and other WT1 expressing tumors. We believe that it has the potential not only to help cancer patients in remission to live significantly longer, but also to provide patients with the opportunity for a more tolerable continuous treatment. We are pleased with the progress of our GPS programs in 2021, really exciting. Earlier this summer, we reported the encouraging data seen to date in the checkpoint blockade combination studies for GPS, and we're eager to continue to advance these studies and further our analyses of the data. Also, we have advanced our registrational Phase III renal study for GPS and have continued and enhanced patient enrollment and opening additional sites in the U. S. And in Europe, and we plan on opening sites outside of the U. S. And Europe as well. As you are aware, we plan to accrue 116 patients in approximately 100 centers globally, and we are fortunate to be working with 1 of the top global CROs, PPD, on the RIDO study. At this time, we expect the interim analysis to occur in the first half of next year, first half of twenty twenty two, provided that the ongoing COVID-nineteen pandemic does not significantly adversely impact our projected timeline for enrollment. Assuming we receive positive data during term analysis, we will then prepare the BLA regulatory submission and submit it to the FDA on a rolling basis due to our fast track designation with potential approval and commencement of commercialization in late 2023. I'd like to speak briefly about the overall landscape of the AML market, a question that many of you have asked, which is one of the themes of today's call. The annual incidence rate of AML is around 80,000 patients in the U. S, Europe, Japan and China. We estimate that approximately 15% of all new patients with an AML diagnosis eventually are eligible for entry into our renal study, and this also represents the total addressable market in the AML CR2 indication. With these patients, we have achieved the 2nd remission. This is the indication of our rebuild study. If GPS is approved in the AML CR2 setting, this would allow for GPS to enter the AML market, and we will then consider a potential label expansion for patients who have achieved their first remission, the CR1 setting. It is absolutely feasible and strategically sensible to consider a GPS study in patients older than 60 years in the AML CR1 space. Moreover, again, assuming positive data in the AML CR2 study, we believe that there is significant opportunity for GPS to be the key antilutemic vaccine immunotherapy in various other settings in AML, such as maintenance after a logenics stem cell transplant, whereby GPS could potentially sensitize, if you will, the donor successfully drafted T cells to prevent post transplant leukemic relapse. This is a key topic Doctors Levy and Ceesich will touch upon today. We believe that it's crucial for us to bring the investment community along as we prepare for upcoming milestones for GPS. As you will hopefully appreciate by the end of today's symposium, GPS is a potential market opportunity in AML alone, not only the AML CR2 setting, but also in the CR1 setting as well as in the post allogeneic stem cell transplant setting. We hope you enjoy the following presentations, and we'll welcome your questions during the Q and A session towards the end of the symposium. With that, it is my pleasure to pass the call on to Doctor. Levi. Hey, welcome everyone. Thank you for your time and for listening. So my name is Yair Levy, and I'm the Director of Hemalignancy Research over at Baylor University Medical Center. And I'm going to give some background on the current treatment of acute myelogenous leukemia, as well as the residual unmet needs that we certainly have in this aggressive cancer. So the treatment of acute myeloid leukemia is rapidly evolving. So treatment of acute myelogenous leukemia or AML for short has been and continues to be a rapidly evolving one over the past decade. Traditionally, when a patient is diagnosed with acute myelogenous leukemia and they're considered fit for induction, in other words, that they're healthy without a lot of comorbidities, they typically receive a chemotherapy regimen called 7 plus 3 or something very similar to it in which we get combinations of a chemotherapy called cytarabine with another chemotherapy called an anthracycline. And this regimen is referred to as an induction regimen. In other words, it's intended to really rapidly reduce the amount of leukemia burden that they have and to allow the bone marrow to regain normal function. So when people present with acute myelogenous leukemia, oftentimes they can present with a low red blood cell count anemia, low cyclic count thrombocytopenia and a low white count called leukopenia. And therefore, they are susceptible to infections as well as complications of bleeding and all the complications of anemia with a low red blood cell count. So the goal with the initial therapy is to put people into what's called a complete remission in which when we look in their bone marrow, we don't see a lot of these leukemia cells and allow the bone marrow to restore its normal function. So when we give this induction therapy, if we don't get any further therapy after people achieve a remission with their induction therapy, typically the leukemia comes back within a few months. So clearly, just getting to a remission is not enough. Therefore, this induction therapy is often followed by what's called consolidation therapy. And again, in folks who are fit, who are able to tolerate a lot of chemotherapy, we typically give something called high doses of cytarabine, but not everyone can tolerate high doses of cytarabine, in which case we'll often have to use something else. And what's typically used are these drugs called hypomethylating agents as both a consolidation and a maintenance strategy. But we know that this treatment will not be curative. When we take a look at leukemia, we often risk stratify people based on the chromosomes of their cancer cell. And we stratify people into what's called favorable disease, intermediate disease and unfavorable disease. But even favorable disease appears to be sort of an oxymoron. Because even with favorable disease, when people receive chemotherapy, about half the people are going to relapse. And once leukemia reappears, patients are often treated with a different chemotherapy regimen. We call that salvage therapy or re induction therapy. And again, they have to receive something else because their leukemia grew through the initial therapy and the definition of insanity is doing the same thing, expecting different results. So there is no consensus on a standard of care of how to give salvage therapy or re induction therapy. But like I said, typically we give something different than they have received before. And then the hope is that they'll enter a second remission. But typically, the first remissions are the ones that last the longest and the second remissions tend to be much shorter. And after a second relapse, that's if we're fortunate enough to get a second remission, most patients will unfortunately pass away from their disease. A third remission is usually considered to be quite rare. So the end result is that the vast majority of patients would usually succumb to their disease by the 2nd anniversary of their initial diagnosis. So even though we think of acute myelogenous leukemia as a cancer that we try to cure, oftentimes we are unable to cure the patient. But the primary goal is still cure. So we treat with curative intent. And unless people have what we call favorable risk disease, then curative therapy often involves consolidation with an allogeneic bone marrow transplant, in other words, a transplant from another donor. So in AML with high risk features, chemotherapy alone is very unlikely to offer a durable response, I. E. Cure. So this is why we do consolidation with an allogeneic bone marrow transplant to greatly increase the likelihood of having this durable response or a cure. And in many cases, it's the only treatment that will actually lead to a lasting remission and a potential cure. But not everybody can get a transplant. So there are issues that can limit the ability of patients to receive a transplant. So in the past, people actually had to have either a complete match or a very close genetic match to their tissue type. If that wasn't the case, then they could develop something called graft versus host disease in which these transplanted cells from the donor not only attack their leukemia cells, but can also attack their normal cells. And these complete matches were not always available. Secondly, a transplant is also a very rigorous procedure and not all patients can tolerate this rigorous procedure. As we know, many cancers and leukemia is certainly no exception occur more often in people who are older as opposed to people who are younger. And these older folks may have some compromised organ function and other comorbidities that make it very difficult for them to tolerate. So because of this rigorous procedure, not all patients can tolerate it well and it's typically reserved for patients who are in good condition. We also usually have an upper age limit of about 75 for what we call mini or non myeloid of allogeneic transplants. And this is not because we want to deny any late therapy, it's just because we know we do more harm than good when people are older. So, we can give transplants to people who are older and by that I mean people between the ages of 6075, but oftentimes those patients are treated with much lower doses of therapy for conditioning. Now, if people can't tolerate a transplant, we can certainly give them some other treatments in lieu of a transplant, but clearly these are not curative therapies. We have made some advances in bone marrow transplantation over the past decade or so. So now we also have the ability to transplant partial match patients and almost everybody has at least a partial match. We're also able to use umbilical cord blood as a source for the transplanted cells. So, it certainly made finding a donor a lot easier than it was maybe a decade ago. But clearly, with these novel sources of cells for the transplant, there can be some additional complications and these are certainly amplified in older folks. So, there are still some folks that even with the availability of a donor may still not be able to undergo a transplant. But even if people can't undergo a transplant, they still have some treatment options. So, transplants, actually, let me even back up. So, for people who can't be transplanted, even if they have a match, there are many reasons for this that I forgot to disclose. So, there are some patients who can qualify for a transplant, but just decline a transplant. Whenever we consent people for transplant, we talk about everything that can potentially happen and there are certainly very real considerations for morbidity and mortality with the transplant. So some people when they hear about this decline of transplant. Some people also may not be able to get it due to the need for having a 20 fourseven caregiver as well as the need to locate themselves at least for the 1st month or 2 near a transplant center, which are usually housed in major metropolitan areas. And we know that not everybody has family member or a friend who can devote that 20 fourseven time to be a caregiver. So for patients that can't get a transplant, there are certainly new drugs that have been approved recently that have demonstrated some response rates and some benefit in patients who have relapsed and refractory acute myelogenous leukemia and can't get transplants. But unfortunately, these are also not curative therapies. And despite the fact that they have efficacy, the efficacy tends to be quite modest. So there has been new developments and improvements in AML, but unfortunately, they have not really demonstrated a very significant overall survival extension. So we were hoping with some of these newer therapies that for patients with AML, both newly diagnosed and relapsed, that we would see a significant extension of remissions and survival. But unfortunately, this disease has proven to be quite difficult. And what we saw over the last few years is these important new advances didn't entirely live up to our expectations. So even patients who undergo a transplant are still at very high risk for morbidity and mortality. It turns out that their median survival remains just a little bit above 2 years if they have any meaningful traits of remaining leukemia cells after induction. So we can actually get very sensitive assays looking for 1 cancer cell even in a million. And this is what we call measurable residual disease. And if people have measurable residual disease after their treatments, clearly they don't do as well as if we can't find any residual disease left. So as a result, there's a large subset of transplant patients and whom transplant is not working great. Actually, if you take a look at deaths after bone marrow transplantation, they're usually not due to complications of the treatment. They're not due to morbidity and mortality of the treatment, but they're frequently due to failure of these allogeneic cells, these cells from the donor to completely eradicate to leukemia. So as we mentioned before, there are patients who can't get a transplant for the various factors that we discussed. And while in a recent trial, the new best toxic therapy did bring response rates close to the level of response rates with intensive chemotherapy, the survival was not increased correspondingly among all these patients. So the average survival of these patients who are considered less fit and cannot get what we call these intensive inductions, tends to be a little bit more than 8 months. And in general, the patients who do achieve a complete remission after induction live an average of about a year and a half. So in patients treated with targeted therapies, survival was significantly extended when they were combined with this intensive heavy duty chemotherapy. However, many of those patients still relapse as well. So just to point out, all of these estimates refer to newly diagnosed patients and whom we're hoping to achieve first remission. And as we mentioned earlier on, survival is certainly much worse for patients who relapse and then achieve a second remission. Those patients survive an average of less than a year and typically it's much closer to half a year. And even with targeted agents, if they're administered in the second line setting, survival is usually measured at months. So, paradoxically, the improvements that we've achieved in acute myelogenous leukemia in general over the last few years may make treatment of relapse patients more challenging and not less challenging, because of their efficacy in leading to complete remissions and a relatively lower toxicity profile that allows them to be used for an extended period of time. These new drugs and treatment tend to be used immediately in the upfront setting. However, since these drugs are rarely curative and we know that transplant doesn't have great success if people still have residual disease, as measured by that measurable residual disease assay, then clearly these results are suboptimal. So what that means is those patients progress while they're already receiving new drugs and procedures and that limits our ability to offer these newer treatments in the second line setting because clearly this leukemia has progressed through those therapies already. So even the transplant is even allogeneic transplant is used much less than second line than it is in first line. So with transplant, we wanted to take our best shot upfront. And in the second line setting, it's much like all of the other therapies, it certainly tends to be less effective. So a patient who relapsed after a transplant stands much less of a chance to significantly benefit from another transplant given that the first transplant failed. At the same time, the cumulative risk of dying from the toxicity of the procedure also increase, if you were to consider a second line transplant. Therefore, this is not something that we utilize usually outside of a clinical trial setting. So there's still a very large unmet need, unmet medical need in acute myelogenous leukemia. And for those reasons, it's still an urgent unmet medical need to find a way to extend survival for relapsed acute myelogenous leukemia patients. So I'm very glad that GPS is actually targeting exactly that. So they're targeting extension of survival in patients who achieve the 2nd complete remission after suffering a disease relapse. And this Phase III VIVAL study will exclude transplant patients. So as I mentioned earlier, patients in their second remission on average live about a half a year. And what we've previously seen with GPS is that they've had an unprecedented 20 month 21 month median overall survival for those patients who receive GPS and best available therapy was right in line with what we had seen historically about 5.5 months. So the REGAL study is expected to have interim data available by around summer of next year and we're all very excited with the prospects of the study, especially for patients in need and for physicians to hopefully use this safe and effective immunotherapy to treat this disease with a high unmet need. But at the same time, as I pointed out, there are additional patient groups in the frontline setting that still need to have an extension of survival. So we discussed these MRD positive post transplant patients who live maybe 1 to 2 years after transplant on average. But what about those even MRD negative post transplant patients? So we can keep a cure in about half of those patients, but about half of them are not cured and will die within a few months to maybe even several years after. So even in these measurable residual disease positive patients in their first complete remission, GPS showed pretty impressive data of 67.6 months median overall survival from diagnosis or greater than 4 years from time of enrollment. And in patients 60 years or older, a median overall survival of 35 months or almost 3 years, which is way higher than anything we had seen with our other best available treatments. So there's clearly a potential for an expanded role of GPS in AML. So for all the reasons that I noted so far, a new therapy that specifically aims to extend survival rather than primarily increase the response rate is needed. Remember, we said in the way beginning that even if we achieve a remission, remission doesn't mean cure. And these remissions can often not last very long. So what I find particularly interesting is that the latest survival data after the first line transplant highlight the role of this measurable residual disease as potentially the most important predictor of survival even in a transplant setting. Think about that. If we are able to eradicate the disease effectively, people are clearly going to do better than if we don't. So it appears to be even more important than the quality of the response, which was traditionally considered the strongest predictor of survival to the point that a complete remission with incomplete hematologic recovery. In other words, we don't see any of these leukemia cells in the bone marrow, but the blood counts maybe did not come all the way back. But now we're getting stronger and stronger signal that even an incomplete response can lead to a lasting benefit if we don't see any evidence of this measurable residual disease. So the fact that the same principle appears to apply in both transplant and non transplant settings really opens up a new space for drug development, indicating drugs targeting minimal residual disease, specifically can play a major role in improving the outcomes of AML patients. And clearly, we've seen this in other acute leukemias, in which there has actually been a drug that's been FDA approved to treat that measurable residual disease positivity and has actually led to better outcomes. So our traditional approach has been to ensure that a drug can affect the complete response and then see whether or not it has an impact on survivor. But now that we have even stronger indications of what impacts survival most, which is this measurable residual disease status, we can start addressing it directly. And GPS might be on the forefront of this new trend. In other words, it can play a key role in a variety of settings, including the transplant setting. As we mentioned before, traditionally, we divided new AML drugs into those that help on the path towards a transplant and those that help patients who can't get a transplant. And right now, we're making big distinctions between 1st remission and second remission with good reason because the prognosis is vastly different. But all of these lines are starting to blur as we better understand the biology of the disease as well as the diagnostic and prognostic information that we are receiving. That's why I find GPS so interesting because of its potential to transcend the historical classifications of AML and target directly the major remaining unmet medical needs, including in many transplant patients. And that is to really try to eradicate all minimal traces of the disease. And I'm going to turn this over to Dragon, who's going to talk more about how GPS works as well as the scientific rationale for this. Thanks, Doctor. Levy. Thank you for your introduction. Okay. Starting the slide show. Okay. The targets for our lead clinical candidates, GPS, is the tumor 1 protein or WT1. The National Institute of Health considers it to be one of the best, not the best cancer targets due to its properties. And those properties are that WT1 is found in almost all human tissues during fetal development, but its expression abates and eventually ceases almost completely in adults. The only time W-two hundred appears in meaningful quantities is when the cells become cancerous. It is present in many cancers, most notably in the 3 indications that we are currently studying in clinical trials: acute myeloid leukemia, malignant bureausothelioma and ovarian cancer. In acute myeloid leukemia, WT1 expression is in fact considered a hallmark of the disease due to its near universal presence in acute leukemia stem cells, so the cells that actually fuel and propagate leukemia. Presence of W-twenty one in cancer cells and its virtual absence in normal cells provides an opportunity for targeting cancer cells without affecting normal cells, which is an approach that is a wholly grave of oncology drug development, because it could potentially allow killing of cancer cells without causing toxicities that limit the amount of the drug that can be administered. However, WH1 is a strictly intracellular protein, so it cannot be targeted by monoclonal antibodies as the whole protein never appears in the cell surface. Only small pieces of protein called peptides appear on the cell surface, and they're embedded in a natural carrier called MHC complex. The depiction of a WT1 peptide embedded in an MHC molecule is shown in the right bottom panel. At the same time, WT1 is not known to trigger an important physiologically active intracellular pathway. So it cannot be targeted by small molecules either. So that's why we are developing a peptide vaccine. Peptide vaccine allows us to generate T cells that can target and kill cancer cells, harboring WT1 inside them and displaying pieces of WT1 peptides that I mentioned before on the cancer cell surface. Next slide. GPS is very carefully designed and we believe much more sophisticated than most anticancer peptide vaccines. Firstly, in GPS, we are not using just a single peptide, but rather 4 of them. And you can see in the circle in the middle, there are these 4 peptides in boxes. Further, because of some overlap and combinatorial potential, we are targeting not one peptide and not 4 peptides, but actually 25 carefully selected and distinct different ones, which are called epitopes, thus greatly enhancing the probability of generating the T cell clone that will effectively recognize at least one peptide on any given cancer cell. Most other cancer vaccines recognize only one peptide molecule. Secondly, GPS is designed to work with multiple HLA types, thus enabling us to use the vaccine in almost any patient, not only patients with a certain type of cell markers. Another major obstacle that GPS is designed to overcome is immunotolerance. WT1, like almost all cancer markers, is recognized by the body as its normal path. So there is little immune response to it, and that's why cancer is such a big problem. We have, therefore, synthesized a peptide to be very similar to the native one, to the naturally occurring one, but deliberately introduced a small difference that makes the immune system recognize WT1 as a foreign marker. Thus, GPS consists of a mixture of 4 peptides, which are fragments derived from the WT1 O line protein. 2 of the 4 peptides have a by design single amino acid mutation embedded, which increases their immunogenicity and is helping to overcome tolerance. The so called heterocytic technology, which allows treatment over a potentially long period of time through administration of booster inoculations. Finally, the peptides in our vaccine are designed to cause an immune reaction from both the immune cells that kill cancer cells, so called CD8 cytotoxic cells and the immune cells that provide long term memory and help to cytotoxic cells, CD4 cells, which extends efficacy of GPS. Next slide. This is a brief overview of our previous study in the exact same patient population that we are addressing in our REGAL trial. So in our previous ML Phase II study, again, the exact same patient population is our Phase III trial, that is patients who achieved second remission or as we call them CR2 patients. We have this debilitating disease where patients typically relapse and die on average within 5 to 6 months. And we observed a striking clinically and significantly clinically statistically significant survival benefit in patients who receive GPS. You can see here an almost 16 month differential survival benefit, 21 months versus 5.4 months. And you can see that we also had 2 fold more than a 2 fold increase in disease free survival in leukemia free survival, which was statistically significant. Next slide. The key with our GPS therapies in AML is monotherapy. Indeed, it seems to be the fact that patients are in remission. As we saw in CR2 patients, similarly patients who achieved their first remission or CR1 had the survival benefit. This is another trial, which was conducted in CR1 patients, and we treated 32 patients in this study. And these patients had a very prolonged median overall survival. As you see here, their survival was 67.6 months from time of the enrollment, and it was observed across all ages with strong CD4 and CD8 immune responses. Now if we separate out the patients 60 years and older, who are most of the AML patients currently, the median overall survival was 32.2 months in Phase I and 35.3 months in the Phase II trial, which was much better than the best standard treatment for this patient population, which is typically about 12 to 15 months. Thus, across all our studies in CR1 and CR2, we have 2 to 3 fold survival benefit versus best available treatment. Next slide. Our most advanced study is our ongoing Phase III pivotal trial in AML patients who achieved second complete remission. That's the RIGO study. And as you've heard from Doctor. Levy, those are patients with a worse prognosis, typically expected to leave around 6 months. We plan to enroll 116 adult AML patients in second remission and randomized them into a study group and control group. In the study group, patients will receive only GPS over a 1 year period. During the 1st 10 weeks, patients will be receiving a GPS vaccination every 2 weeks, then once a month for 6 months and during the final vaccination period, once in a month and a half for the remainder of the year. Patients randomized to the control group will be treated per investigator's choice because there is no standard of care and there is a great variability in how these patients are treated in the clinic. I will touch upon that again later, but the very important point is that all approved available treatments cause sooner or later, as Doctor. Ray pointed out, significant levels of toxicity, primarily by suppressing production of immune cells and platelets, which is the same effect that leukemia has. So these patients really are between a rock and a hard place. GPS, on the other hand, does not cause suppression of the production of immune cells and blood Patients on the trial will be treated with GPS for up to a year and followed up closely for approximately 2 years altogether. The main outcome of the trial will be a comparison between the length of survival in the GPS treated patients and in the control group. Next slide? As Doctor. Haley pointed out, there are many treatment modalities for AML, and how the patient is treated depends on many factors, including whether the patient is newly diagnosed or relapsed, the patient's age, how healthy they are in general, the genetic makeup of their leukemia cells and more. Without getting into a long and complex review, I'd just like to point out that although there are many treatment options for both newly diagnosed and relapsed patients to put them into remission, there is a relative positive option that extend the survival after remission. In fact, you may notice that observation is a major option for patients in remission. As you will see, GPS is targeting that space where patients have the highest unmet medical need, post remission state to extend survival. Next slide. Now let me give you a high level overview of how GPS fits into the current treatment paradigm. As I said before, the renal trial patients are patients in the second remission. So they already have leukemia, they're treated, they then relapsed and then achieve the second remission. Therefore, we are here focusing only on relapsed AML patients in this slide. So basically, patients younger than 75, as Doctor. Levy pointed out and who are in good shape, meaning good overall condition without major comorbidities, will be put on a pathway to transplant. They will get high intensity chemotherapy with the goal of putting them into remission. Once they are in remission, they will be assessed again for feasibility of bone marrow transplant. Some patients will have a deteriorating condition due to the toxicities of the intensive therapy and will no longer qualify for transplant. Many of those patients will have already had a transplant in the 1st complete remission and most physicians like Doctor. Levy see no benefit in attempting the same very high risk procedure that has already failed once. For some patients, their insurance will require that patients meet very stringent medical requirements and will not cover the cost of their transplant. Some patients will not be able to go through with the transfer due to socioeconomic conditions that Doctor. Riebe described. And finally, some patients will decide not to go through with the transplant due to personal preferences. So as a result, fewer than around a quarter of the patients who qualify for a transplant in second remission will go through with it. All patients who can't proceed with the transplant are candidates for the renal trial. Now, if you look at the right hand side where we described patients older than 75 and those who are younger but have significant comorbidities, You will see that they are not considered for a transplant and they will receive less intensive therapies because of their general condition. Those less intensive therapies have less toxicities, so they can be treated repeatedly these patients. However, as Doctor. Will explained, less toxicities does not mean no toxicities. So with protracted use, toxicities accumulate and eventually most patients have to at least pause, if not completely stop those less intensive treatments. Those patients are candidates for the renal trial also. So altogether, as we can see, majority of CR2 patients are candidates for our pivotal Phase 3 trial. Next slide. Now this is something that we found very exciting and very interesting. We would like to share with you some insights from a major paper that has recently been published in the Journal of Bone Narrow Transplantation. As we said, almost all the patients who get bone marrow transplant, if at all possible, because that's the only potential recurrent procedure for MUNS for the AMR patients. For that reason, we designed our pivotal trial to not include patients who are slated for a transplant. However, this new study that included 4,280 AML patients treated in more than 450 blood and marrow specialized cell phone centers in the U. S. And around the world between 2,007,2015 provides some key insights. This analysis has demonstrated that the benefit of transplant does not accrue equally to all AML patients who receive it. When AML patients enter into remission, the quality of all remissions is not the same. Patients in remission do not have leukemia cells in their blood and bone marrow that can be observed under a microscope. But some patients have complete recovery of their normal blood elements and some don't. That's what Doctor. Healy talked about too. Those who have complete recovery of their normal blood cells are said to be in a complete remission or CR. And those who don't are said to be in a complete remission with a complete peripheral blood recovery. That's referred to as CRI. It has been long known that patients with CRI have a worse prognosis than patients in CRI. But beyond this, for those patients in remission, in more recent years, we developed technologies to identify the presence of small numbers of leukemia cells that can't be detected with a microscope, but they can be identified by their genetic materials presence in blood and other chemical characteristics, their specific metabolities. If those genetic and chemical elements are present in detectable amounts, patients are set to have minimal residual disease or as Doctor. Griri referred to, measurable residual disease. These are both the same terms and the acronym is MIB. Now we have learned from the retrospective analysis that transplants cure about half of the patients only if they have no MRD. In cases of both patients with CR and CRI, but only a bit more than 1 third of patients with MRD can be cured. Maybe even more important, the median survival for patients with MRD is just about 1 year. And if they did not have complete peripheral blood recovery after the treatment and adjusted more than 2 years if they had complete peripheral blood recovery. Now consider these results in the context of GPS results that we've shown a few slides before. GPS patients had complete responses and they were MRD positive, but were not even eligible for transplant. So even without a transplant, their median survival was 48.5 months, about 2x longer than for the same category of patients who actually received the transplant. Next slide. The results from the retrospective data analysis as you just described have very important implications for GPS clinical development in leukemia. They once again confirm that GPS is not that GPS not only has potential for CR2 patients, but it could be equally important in the CR1 patient population. The pool of addressable patients is further enhanced by the fact that we can now identify CR1 patients who actually undergo a transplant, thus who are less likely to benefit from it, and for whom GPS could potentially significantly extend survival. We are referring to MIB positive patients here. Yet another avenue of expansion is patients with CRI as opposed to patients with CR only, and we are already including patients with a modified CRI into the liver trial, allowing us to study the potential for GPS in the CRI patient population as well. All in all, we believe that GPS has potential for an AML patient population that is several fold larger than what we initially focused on in the REGAL trial, and we are beginning to explore those this further clinical development opportunities. Next slide. I will now briefly address our additional ongoing trials. We are conducting a trial in advanced ovarian cancer and another trial in molybdenum pleural mesothelioma. Both trials are in combination with checkpoint inhibitors. Expected potential synergy between GPS and checkpoint inhibitors is an important avenue of clinical research for us. T lymphocytes are known to perform immunosurveillance for cancer by patrolling the body and killing cancer cells when they recognize However, many cancer cells learn how to prevent T cells from killing them. They build molecular breaks that engage with molecular structures on T cells and they're already going to stop. Checkpoint inhibitors, drug called checkpoint inhibitors act by blocking those breaks. At the same time, as discussed earlier, GPS is specifically designed to teach T cells how to recognize cancer cells and very successfully so. Thus, the immune system needs to meet 2 requirements. T cells need to be able to recognize cancer cells, which is provided by GPS, and once they recognize them, to proceed to killing them, meaning that the brakes need to be blocked, which is what checkpoint inhibitors do. In some cancers, there are few molecular brakes. So the main issue is that T cells don't recognize cancer cells. That's the case with acute malignant leukemia, and that's why we don't need to combine GPS with checkpoint inhibitors for that disease. But in some, like ovarian cancer in mesothelioma, there are both problems. T cells recognize cancer cells poorly and cancer cells have molecular breaks. In dose cancers, GPS and checkpoint inhibitors will have limited efficacy on their own, but may work much better as a combination. Thus to summarize the scientific rationale here is the potential immunodirological and pharmacodynamic synergy between GPS and checkpoint inhibitors, whereby the negative influence of the tumor microenvironment is mitigated by checkpoint inhibitors and thus allows the patient's own immune cells specifically sensitized against WT1 by GPS to invade and destroy cancer cells. But to properly check that hypothesis, we first need to know that GPS and checkpoint inhibitors when combined are safe for patients. At this early stage of clinical development for the combination, our primary goal has been to ascertain whether GPS can be safely combined with the best known checkpoint inhibitors, tembrolizumab and nivolumab. And I'm happy to report that the answer so far has been a resounding yes. There appears to be no difference in toxicities between the patients who receive checkpoint inhibitors alone and those who receive checkpoint inhibitors in combination with GPS. At this point, we feel confident, barring some unexpected new development that GPS indeed can be safely combined with checkpoint inhibitors. But in addition to safety, which is our primary goal in this study, we have also seen early indications of efficacy. In the ovarian cancer trial, we have treated to date 11 patients, all of whom are resistant to the standard of care therapy and very much so. All patients were also resistant to second line treatments and 1 third of them to 3rd and 4th line treatments. So patients of that type unfortunately die within 9 to 12 months inherited. In our trial, they are already alive more than 9 months, and they are continuing with the trial. So we are looking forward to continuing to analyze them and keeping you updated. When treated with pembrolizumab alone, this type of patients typically rapidly progress within approximately 63 days. The addition of GPS has extended progression free survival to approximately 83 days so far and the trial continues. As I said before, the combination of safety and efficacy allows these patients to continue receiving both GPS and pembrolizumab longer, which hopefully translates into survival benefits, which we will see as the trial progresses. And we have also confirmed another major point in this study. GPS really does teach T cells how to recognize cancer cells. In fact, the number of T cells that recognize cancer cells increased by as much as 200% or more. So again, 2.54 dollars after GPS treatment. Next slide. We also have an ongoing trial of GPS in combination with nivolumab, another checkpoint inhibitor, which is an investigator sponsored trial at Memorial Sloan Kettering Cancer Center. This trial is in malignant blood pleural mesothelioma, a disease defined in part by its expression of WT1 targets. We have had 4 evaluable patients to date in this trial, so the data is most anecdotal at this point. But we can again say that the combination is safe and there are other indications of efficacy and immune response as shown in this slide. The median overall survival so far has been 8.3 months for the GTS treated patients. And interestingly, one of the 4 patients suffers from the worst subtype of mesothelioma, which is called sarcomatoid mesothelioma, and that patient is still alive after 25 months, which is several fold longer than expected. Next slide? In closing, Celesys' lead product, GPS, is a highly differentiated immunotherapeutic that has been given to over 150 patients with good tolerability and has shown real clinical benefit in extending the lives of AML patients in remission, which is a growing unmet medical need as well as in other indications. Our ongoing Phase III legal study has been progressing well, and we have a world class experts monitoring its progress, and we have full support from our prominent scientific advisory board. It is important to point out here that we that when it comes to the gold standard endpoint for oncology trials, which is overall survival, safety and efficacy go hand in hand. As we have discussed, currently there are many cancer drugs that have very rare applications in eliciting responses, meaning curing cancer cells. But unfortunately, patients don't live that much longer because those drugs and procedures result in toxicities that mandate early stopping of their use and the cancer then returns to interventions. Today, the main remaining challenge in oncology is to be able to keep the patients on treatment for an extended period of time, thus significantly expanding their survival. GPS has been up to that task so far, and we are looking forward to amassing even more confirmation, hopefully, the data outcome, which could lead to an eventual approval. The truly urgent time in AML has been confirmed once again by the largest data analysis of patients transplanted for their AML. The insights garnered from the publication underlines the additional opportunities for GPS. That's why we are performing a pivotal trial in acute malignant leukemia, but it's just our first foray. As we have seen, GPS has multiple more opportunities, and there is a serious need for it in several more AML settings in addition to the 1 in the current renal trial. We are following the AML trial with 2 additional solid tumor cancer trials, which although in early stages have already demonstrated that GPS generates surveillance T cell, that it can be safely combined with other key immunotherapeutics and that it shows early indications of expanding patient survival. We have also demonstrated our operational ability as a company to handle a large multinational trial, which is renal, across continents and to satisfy requirements of multiple international regulatory agencies. So with all of that, we are on a very good track. Thank you, Duragen. And we will now address the questions that have been submitted. In sake of time, I think I will answer a few of them and I'll ask Doctor. Riehme to also take some of the other questions. So one question is regarding the market size of CR1, CR2 and if the company intends to do a study in CR1 and post transplant. The annual incidence rate, as I mentioned, AML is roughly about 80,000 patients in the U. S, EU, Japan and China. And in the U. S, the total number of newly diagnosed patients with AML is roughly 21,500 patients. And we estimate that the number of adult patients of any age with AML in the U. S. Per year who successfully entered the CR2 setting conservatively is around 2,000 patients. So typically, somewhere in the 15th percentile of approximately close to 5,000 patients in the rest of the world outside of the United States. So we estimate the number of CR1 patients to be approximately 16,500 patients in the U. S. Alone. It's approximately 38,000 patients rest of the world. So as long as patients are really in remission after initial treatment, patients may potentially be candidates to get GPS. And as far as a study design of CR1 or post transplant, as I mentioned in my early remarks, we absolutely will expand in the CR1 setting. We're working internally with the Board Science Committee, which is led by Doctor. David Scheinberg of Memorial Sloan Kettering, whose lab discovered GPS on a life cycle plan for GPS. The recently published analysis of the data that Doctor. Levy and Dragon talked about for AML patients is very intriguing, and we believe that it indicates that there's an opportunity for GPS in the AML market landscape beyond the indication of the legal study, which we definitely intend to explore. So as I've been saying for some time now, it's my personal belief that there is significant opportunity for GPS to be the anti leukemic vaccine immunotherapy in various other settings in AML, as I mentioned, such as in maintenance, allogeneic stem cell transplant or in the CR1 setting. Obviously, we have done some pricing reimbursement work as well, so I cannot talk about the revenue potential as we have not provided any guidance on that. But rest assured, we have been doing everything to ensure that GPS will ultimately be a successful immunotherapy. The next question is around if you can provide some guidance and updates on the legal study enrollment and the confidence on the interim data. As I've mentioned in the past, we do not provide updates on enrollment and we've indicated that we expect to get the interim data by the end of the first half of next year, so by the summer of 'twenty two, subject to any delays due to the continuing COVID-nineteen pandemic. But we will provide meaningful updates when appropriate, and it's going to be done in concert with the data monitoring and steering committees. I've mentioned many times in the past that the independent data monitoring committee, in particular, has a lot of weight in the regional study. They will be able to independently and directly liaise with the FDA. So we will be very careful what we will announce to the public. We'll be very careful to seek information from the data monitoring committee because we want that body to be independent and provide guidance, and we do not want to jeopardize the integrity and the hopeful success of the RIDELL study by providing data and making announcements that could potentially harm the success of our RIDELL trial. And I really hope you can appreciate that. The other question is around the delta strain and as we're opening sites, obviously, COVID is still there. And so far, we've been very careful to mitigate risk, and that's why we have opened up additional sites. Initially, as you may recall, we plan to open 50 clinical sites. It was pre COVID time, but we've gone now to 100 sites to really mitigate exactly that and the potential time delay. So at this point, where I'm standing today, I can tell you that by summer of next year, we believe we will have interim data, which will hopefully allow us then to pursue the approval process for GPS in acute myeloid leukemia. One more question for me is around the 3 d Medicines agreement and the question where we stand there. We provided the most up to date information regarding milestones from the 3 d Medicines license agreement in our earnings release last week. As you know, to date, we have received a total of $9,500,000 and we expect to receive further milestone payments this year and thereafter. The total deal is $202,000,000 plus royalties. So we have received close to $10,000,000 $9,500,000 to be exact. And the relationship is very strong and I have to say very collaborative and I think they're a fantastic partner. I think I'll turn it over to some questions that are intended for Doctor. Levy. Doctor. Levy, one question that has come up is sort of if you want to talk a little bit about your confidence on the GPS data in AML, but also in the solid tumors to date and sort of your feeling around that? Yes, absolutely. So, I mean, obviously, I am not qualified to speak about solid tumors, I think, to the gene doctor. But I can tell you that the preliminary data that we see looks fantastic. So whenever you have 3 to 4 times, 3 to 4 times the expected survival, even in a non randomized manner in a uniformly deadly disease like acute myelogenous leukemia, you certainly take notice. Now clearly, there is need for confirmatory trials that document this in a prospective manner. And certainly in a randomized manner consider randomizing to best available therapy. But what we've seen so far is certainly nothing short of spectacular and hopefully that that data can be maintained. I would have a lot more confidence in something that has extended the expected survival by 3 to 4 times than I would something that led to a 50% improvement in survival. So here we're talking 300% to 400%. So I feel like that difference is more likely to be maintained. Even if it gets whittled down, it's still a very meaningful difference. And then, even the other two questions are, assuming that GPS does get approved for AML, would you administer the drug to all your AML patients to specific type? If you can just talk a little bit about Well, again, we have to see what the final data looks like and what that patient population looks like and then also what the FDA label would be. So there's a lot of things that actually go into that. But one of the things that I don't know how much this was stressed, but this is certainly a very important point to stress out is the tolerability profile of this treatment is spectacular. So the reason that oncology exists in its own field is because we use very toxic drugs in order to try to eradicate cancer. This is an extremely benign safety profile. And as I mentioned early, most cancers occur in people who are older as opposed to people who are younger and people who are older tend to have more comorbidities. So to have a side effect and tolerability profile as benign as this would certainly lend itself to be used in just about any patient. There wouldn't necessarily be a patient that has performance status or the ability to tolerate treatment that's not very good, they couldn't necessarily get this therapy. Great. Thank you, Doctor. Levy. I think maybe one more comment I would like to make is that the questions on this symposium today are around GPS. There was one question around NPS and the update on the licensing. I think the only comment I want to make there is that please stay tuned and we should be having news here very soon on the NPS front. But today's session is around GPS. I think those were the questions that we have received. And again, I think I would like to thank everyone for your questions and for tuning into our investor symposium. Before we end today's webinar, I'd really like to reiterate our belief that GPS has the potential to change the face of immunotherapy as we know it today. It has the potential not only to help cancer patients in remission, but really significantly live significantly longer, but to also provide patients with the opportunity for more tolerable continuous treatment. And as Doctor. Levy mentioned, the safety profile, tolerability profile is really favorable. In conclusion, the clinical data and immune response profiles from the Basket study of QPS in combination with pembrolizumab for treating WT1 positive advanced ovarian cancer as well as the Phase 1 open label investigator sponsored clinical trial of GPS in combination with Bristol Myers Squibb's anti PD-one therapy of devo in patients in MPM, molybdenumab are really encouraging and we're looking forward to continuing to analyze updated data from these studies. Furthermore, as you hopefully appreciated today, GPS is a market potential, not only in the AML CR2 setting, but also in the CR1 setting as well as post allogeneic stem cell transplant. And we have not addressed all the other WT1 expressing tumor types. As you may recall, there are around 20 of them. Finally, I would like to emphasize how grateful we are to all our shareholders for the continued support bestowed upon sellers. This is not a sprint, it's a marathon. And I know you have stood by us, and I really hope that you have seen over the past months years that we have really taken the ship, if you will, on a show that's really going towards success. Our team has worked diligently and extremely hard to get to where we are today, but still the entire car is still coming and hopefully that's going to be in the summer of next year. We ended the 2nd quarter with approximately $21,000,000 in cash on hand and recorded further revenue from the 3 d Medicines license agreement. We're a small but experienced team that is dedicated and committed to seeing our lead asset, our lead clinical candidate GPS through development, so that it may one day really make a difference in patients' lives. And that's going to be the day that's going to make us indeed very proud, and I'm sure it's going to make you very proud as well to be part of the CELUS shareholder base. With that, I really thank you very much for tuning in today.