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spk09: Welcome to the FATE Therapeutics Second Quarter 2022 Financial Results Conference Call. At this time, all participants are in a listen-only mode. This call is being webcast live on the Investors section of the FATE's website at fatetherapeutics.com. As a reminder, today's call is being recorded. I would now like to introduce Scott Walshko, President and CEO of FATE Therapeutics.
spk08: Thank you. Good afternoon and thanks everyone for joining us for the faint therapeutic second quarter 2022 financial results call shortly after 4pm Eastern time today we issued a press release with these results, which can be found on the investor section of our website under press releases. In addition, our form 10 Q for the quarter ended June 30 2022 was filed shortly thereafter. and can be found on the investor section of our website under financial information. Before we begin, I'd like to remind everyone that except for statements of historical facts, the statements made by management and responses to questions on this conference call are forward-looking statements under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties, that can cause actual results to differ materially from those in such forward-looking statements. Please see the forward-looking statement disclaimer on the company's earnings press release issued after the close of market today, as well as the risk factors included in our Form 10-Q for the quarter ended June 30, 2022, that was filed with the SEC today. Undue reliance should not be placed on forward-looking statements which speak only as of the date they are made as the facts and circumstances underlying these forward-looking statements may change. Except as required by law, Faith Therapeutics disclaims any obligation to update these forward-looking statements to reflect future information, events, or circumstances. Joining me on today's call are Dr. Wayne Chu, our Chief Medical Officer, Ed Dulac, our Chief Financial Officer, and Dr. Bob Ballamer, our Chief Research and Development Officer. Today, we will highlight key objectives we are striving to achieve during the next six months with our off-the-shelf, iPSC-derived NK and T-cell programs for the treatment of cancer. Our top near-term focus remains our B-cell malignancy franchise, where we are seeking to advance into late-stage development for relapsed refractory aggressive lymphoma and to assess the feasibility of treating newly diagnosed patients in a community setting with FT596 plus ARDSHOP without PSY flu conditioning chemotherapy. We're also approaching key inflection points under our IPS-derived CAR-NK and CAR T-cell collaborations with Janssen and Ono, where multiple programs are poised to advance toward IND submission. And with numerous hurdles continuing to challenge the manufacture and development of patient and donor-derived engineered cell therapies, We continue to believe iPSC technology is the winning platform for mass production of off-the-shelf multiplex engineered cell products. We look forward to sharing first-in-human clinical data from our engineered NK and T cell cancer immunotherapy programs and to unveiling new multiplex engineered IND candidates that further incorporate novel synthetic functionality for the treatment of cancer during the next six months. In our pursuit of pivotal readiness with our IPS derived NK cell programs for relapse refractory aggressive B cell lymphoma, we continue to make great strides across our clinical, regulatory, and manufacturing operations. Under our phase one study of FT596 in combination with rituximab, we observed a favorable safety profile in our single dose and two-dose escalation cohorts at up to 900 million cells per dose. And we are continuing to further evaluate dose and schedule to maximize therapeutic index. To that end, we have initiated enrollment in a single dose and two-dose cohorts at 1.8 billion cells per dose. And upon clearance of dose-limiting toxicities, we are set to open a three dose cohort at 1.8 billion cells per dose to evaluate a further increase in cell load. Eligible patients are permitted to receive additional cycles of treatment and the clinical protocol allows for further dose escalation and for the initiation of multiple expansion cohorts at any cleared dose and schedule. On the regulatory front, Our FT516 RMAT type B multidisciplinary meeting with the FDA is scheduled for the third quarter. The agenda includes a discussion of multiple registrational pathways that may be available for our off-the-shelf IPS-derived NK cell programs for relapsed refractory aggressive B cell lymphoma, including in patients whose disease is refractory 2, or have relapsed following prior treatment with FDA-approved CD19-targeted CAR T-cell therapy. Importantly, no standard therapies are available for these patients, and real-world data continue to indicate that these patients have extremely poor treatment outcomes. With respect to manufacturing, our state-of-the-art, multi-drug product manufacturing facility located in Poway, California, has opened. and is poised for GMP production with aseptic process validation now successfully completed and engineering runs ongoing. The facility is designed to supply drug product for the conduct of pivotal studies and initial commercial launch and is located on the campus of the company's corporate headquarters, allowing for full operational integration among the technical operations, regulatory equality, research and development, and corporate teams. Across our clinical, regulatory, and manufacturing operations, we remain well positioned to optimize dose and schedule of FT-596, to chart a regulatory pathway toward approval with input from the FDA, and to mass produce drug product for pivotal study execution from our state-of-the-art GMP facility. We look forward to providing a comprehensive update for our IPS-derived NK cell programs in relapsed refractory B-cell lymphoma as we continue to progress these three key franchise pillars over the coming months. In addition to delivering transformative outcomes to heavily pretreated patients with relapsed refractory B-cell lymphoma, We are also seeking to reach patients in the community setting who might benefit from earlier treatment with cell-based cancer immunotherapy. We believe the use of intense conditioning chemotherapy that accompanies the administration of both autologous and allogeneic cell-based cancer immunotherapies is a significant barrier to broader patient access. and that the delivery of off-the-shelf cell therapies in the community setting as an add-on to frontline immunochemotherapy regimens without side flu condition and chemotherapy may hold significant therapeutic value for many patients. To that end, we have worked with key opinion leaders and investigators to finalize a clinical protocol that brings FT596 to newly diagnosed patients with aggressive lymphomas in the community setting in combination with RCHOP, the standard first-line treatment regimen. The clinical protocol assessing FT596 plus RCHOP in patients with newly diagnosed aggressive lymphoma has been submitted to the FT596 IND. The treatment schema allows for the administration of up to six doses of FT596 Without side flu condition and chemotherapy, each one dose of FT-596 administered with each of six standard cycles of RCHOP. Study startup activities are ongoing at multiple sites, and we expect to begin treating patients with FT-596 plus RCHOP in the second half of 2022. In addition, as part of our quest to substantially reduce or eliminate the requirement for conditioning chemotherapy in the field of cell-based cancer immunotherapy and reach patients earlier in care, we continue to research new synthetic functional elements for integration into our product cannabis that can harness a patient's intact immune system to potentiate the activity and persistence of adoptively transferred cells. At the American Association for Cancer Research in April, we unveiled our proprietary alloimmune defense receptor, or ADR, which selectively targets 401 expressing activated immune cells. In preclinical models, we showed that ADR-armed, iPSC-derived NK cells uniquely expand, persist, and maintain anti-tumor activity in vitro in the presence of alloreactive T cells. These preclinical data provide proof of concept that ADR arm cell therapies have the potential to persist and induce potent anti-tumor activity without requiring a patient to undergo conditioning chemotherapy. During the second half of 2022, We expect to present new preclinical data for our ADR technology and highlight its integration into a next generation NK cell product candidate. Turning to our collaborations with Janssen and Ono, we continue to show strong momentum in bringing multiplex engineered IPS-derived CAR-NK and CAR-T cell collaboration programs to patients for the treatment of hematologic malignancies and solid tumors. and we are reaching key inflection points where multiple candidates are poised to advance toward IND submission. Under our collaboration with Janssen, entered into in April 2020, Janssen designated and contributed novel binding domains targeting four tumor-associated antigen programs, two of which are directed to hematologic malignancies and two of which are directed to solid tumors. Janssen maintains the option subject to its payment of an option exercise fee prior to IND submission to initiate worldwide clinical development of and to commercialize collaboration products under each antigen program. We maintain an opt-in right to co-commercialize and share equally in profits and losses of collaboration products in the U.S. under each antigen program. In May, Janssen exercised its option on a first antigen program, triggering a $10 million payment to FAPE, and we have now advanced a second antigen program to the stage of option exercise decision. We are currently working with Janssen to prepare and submit two IND applications, one for each of these two antigen programs, for off-the-shelf IPS-derived CAR-NK cell collaboration products. Under our collaboration with Ono, entered into in September 2018, Ono has contributed novel binding domains targeting one solid tumor-associated antigen for development of off-the-shelf IPS-derived CAR-T cell therapy. Upon the achievement of a specified preclinical milestone, OwnOath retains the option, subject to its payment of an option exercise fee, to conduct worldwide clinical development and commercialization, and we maintain the right to co-develop and co-commercialize collaboration products in the U.S. and Europe. We have now initiated the generation of the master cell bank for a multiplexed engineered, IPSC-derived CAR-T cell collaboration candidate and are positioned to achieve the specified preclinical milestone and initiate IND-enabling activities later this year, at which time ONO has the right to exercise its option subject to its payment of the option exercise fee. Given the success we have achieved working together on a first solid tumor antigen program, we expanded our collaboration with ONO in the second quarter to add a second solid tumor antigen program and to include the development of both CAR-NK and CAR T cell collaboration candidates. We are very pleased with the success we've achieved with Janssen and Ono in developing multiplex engineered IPS derived CAR-NK and CAR T cell product candidates for both liquid and solid tumors. We are poised to achieve significant milestones in connection with option exercises by Janssen and Ono, and advance multiple collaboration products toward IND submission over the next six months. During the second half of 2022, we will take the opportunity to showcase our leadership in the development of iPS-derived NK and T-cell cancer immunotherapies, including for solid tumors at the Society for Immunotherapy of Cancer annual meeting in November. and for hematologic malignancies at the American Society of Hematology annual meeting in December. At CITC, we look forward to highlighting our clinical progress and innovation under our Solid Tumor Franchise, where we continue to invest in building a deep pipeline of multiplexed engineered IPS-derived CAR and KNT cell product cabinets, including through the development and incorporation of new synthetic elements designed to overcome critical barriers that limit the effectiveness of cell therapy, such as cell homing, tumor escape, and immunosuppressive tumor microenvironment. In the second quarter, I am pleased to announce that we treated the first patient in our multi-center phase one study of FT536, the company's first ever iPSC-derived CAR-NK cell program for solid tumors. FT536 incorporates a novel CAR targeting the major histocompatibility complex class 1 related proteins A and B. High expression of MgA and MgB proteins, which is induced by cellular stress damage or transformation, has been reported on many solid tumors. However, protolytic shedding of the alpha 1 and alpha 2 domains of these proteins is a common mechanism of tumor escape. FT536 uniquely targets the Alpha-3 domain of MycAmycB, which is resistant to shedding and therefore represents a promising strategy to overcome tumor escape. We believe the product candidates novel mechanism of action, including its ability to target other antigens in combination with monoclonal antibody therapy, IPS-derived CAR T-cell product candidates for solid tumors that are advancing toward IND-enabling studies, which include an IPS-derived CAR T-cell product candidate that incorporates seven synthetic modalities to overcome tumor heterogeneity, promote trafficking, and induce activation in response to repressive signaling in the tumor microenvironment. We believe we have one of the most novel, diverse, and sophisticated cell-based cancer immunotherapy pipelines for solid tumors, which is uniquely enabled by our proprietary IPFC product platform. At ASH, we are also excited to share clinical data across our hematologic malignancy franchises. In addition to our NK cell franchise in lymphoma, We continue to see investigator enthusiasm for off-the-shelf IPS-derived CAR T-cell program FT-819. On multiple fronts, FT-819 is truly a unique first-in-class product candidate. Not only is it the first-ever IPS-derived T-cell therapy to undergo clinical investigations, FT819 incorporates a biallelic insertion of an anti-CD19 CAR transgene into the T-cell receptor alpha constant locus with complete disruption of T-cell receptor expression. And its CAR construct is comprised of a novel 1XX co-stimulatory domain that is designed to balance T-cell activation and exhaustion. In the setting of relapsed refractory AML, we look forward to sharing clinical data with FT538, both as a monotherapy and in combination with daratumumab in the high-dose, multi-dose cohorts, where we are now treating the first patients in three-dose cohorts at 1.5 billion cells per dose. And finally, in setting of relapsed refractory multiple myeloma, While dose escalation with FT576 is ongoing in the low dose cohorts and with single dose treatment schedules, we look forward to seeing the initial activity profile of our novel BCMA binder and to assess the multiple potential benefits conferred in combining FT576 with DAR2MAP, including enabling multi-antigen targeting of BCMA and CD38 as well as reducing competition from endogenous immune cells for cytokines to further potentiate the functional persistence of FT576. I would now like to turn the call over to Ed to highlight our second quarter financial results.
spk06: Thank you, Scott, and good afternoon. Faith Therapeutics is in a strong financial position to advance our pipeline. Our cash, cash equivalents, and investments at the end of the second quarter of 2022 were approximately $581 million. In the second quarter of this year, our collaboration revenue derived from our partnerships with Janssen and Ono Pharmaceutical increased by $5.1 million to $18.5 million, compared to $13.4 million for the same period last year. Research and development expenses for the second quarter increased by $33.3 million to $81.3 million, compared to $48 million for the same period last year. The increase in our R&D expenses was attributable primarily to increases in employee headcount and compensation, including share-based compensation, investments made in equipment and materials, and in expenses associated with R&D fees and third-party consultants. General and administrative expenses for the second quarter increased by $8.2 million to $20.4 million, compared to $12.2 million for the same period last year. The increase in our G&A expenses was attributable primarily to an increase in employee headcount and compensation, including share-based compensation, and legal expenses. Total operating expenses for the second quarter are $101.7 million, which includes $20.5 million in non-cash share-based compensation expense. Please note that in connection with the development of our off-the-shelf IPSC-derived CAR T-cell product candidate FT819, we previously achieved the first clinical milestone set forth in our amended license agreement with Memorial Sloan Kettering Cancer Center, thereby triggering a first milestone payment to MSK in 2021. Up to two additional milestone payments may be owed to MSK based on subsequent trading values of the company's common stock, ranging from $100 to $150 per share. We assess the fair value of these contingent milestone payments currently valued at $9.9 million on a quarterly basis. In the second quarter, we recorded a non-cash $5.9 million non-operating benefit associated with the change in fair value. Our net loss for the second quarter of 2022 was $76.1 million, or 79 cents per share. Finally, our year-end cash guidance remains unchanged, and we expect to end this year with at least $400 million in cash, cash equivalents, and investments. This does not include potential success-based milestone payments from our collaborations with Janssen and Ono Pharmaceutical. I would now like to open the call to questions.
spk09: Thank you. Ladies and gentlemen, the floor is now open for questions. If you have any questions or comments, please press star 1 on your phone at this time. We ask that while posing your question, you please pick up your handset if listening on a speakerphone to provide optimum sound quality. Please hold whilst we poll for questions. Thank you. Your first question is coming from Tazeen Ahmed of Bank of America. Tazeen, please ask your question.
spk03: Hi. Good afternoon and thanks for taking my questions. Maybe a point of clarification for this RMAP meeting that you scheduled this quarter for 516. Can you just give us a little bit more visibility on what you'll be discussing at the meeting, and when should we expect to hear back how that meeting went? Thanks. I would have a follow-up after that.
spk08: Sure. I mean, so I'm not going to get into the details of the regulatory discussion, but suffice it to say, We are going to discuss multiple different registrational pathways for our IPS-derived cell product candidates. We think those registrational pathways are applicable to both FT-516 as well as FT-596. In particular, while we will focus on some development pathways that are more broadly applicable, Specifically, I think we will drill down on the patient population that is post-CART T-cell therapy, as we believe that is a potential fast-to-market strategy. And we would like to confirm specifically a study design with the FDA in that patient population.
spk03: Okay. Thanks for the color. And then... I'm sorry.
spk08: With respect to timing, usually you will receive minutes from the FDA documenting the conversation and the findings within about 30 days of it.
spk03: Okay. And then I guess you'll wait for the minutes to advise us of what's next.
spk08: Correct. I certainly don't want to jump the gun on an FDA discussion.
spk03: Yeah, sure, of course. Understood. And then as it relates to the 596 and rituximab study, you know, the $1.8 billion study cell dose cohort. When do you think we can start to see data from that? And, you know, what type of data should we expect to be good data based on what you're looking for? Sure.
spk08: I'll turn it over to Wayne to comment on it. With respect to, you know, a little bit in terms of what do we think would be good data, I think, again, feasibility that we can give FT596 in combination with RCHOP and with outside flu would be interesting. And, again, many of those validation sets of data will be based on translational. So for instance, we can continue to look at FT-596 and how it performs in the first cycle versus the sixth cycle of RCHOP, and certainly we can compare that to how FT-596 performs from a translational perspective versus side flu, given the number of patients we've treated. I'll let Wayne talk about the study a little bit.
spk05: Yeah, so with respect to the study, As was mentioned, the FT596 protocol allows for a lot of different options with respect to the dosing schedule, right? So currently we're initiating a dose cohort where we are administering FT596 at 1.8 billion cells per dose administered twice in a cycle. And once we clear that, then the plan will be to further go in different directions with respect to dose and schedule optimization, including the possibility of further dose escalation as well as giving more doses, i.e. three doses in a given treatment cycle. That's in the relapsed refractory setting. That's in the relapsed refractory setting, correct.
spk08: In the frontline setting.
spk05: In the frontline setting, it's a little bit different because we're giving a single dose of FT596 following a standard cycle of RCHOP. You know, as far as like data availability, it all depends on, you know, how quickly we can enroll just knowing the fact that, you know, getting initial responses will take some time just based on what we have for protocol. So as soon as we have that data, we will obviously be sharing that with you.
spk01: Okay. Thank you very much.
spk09: Thank you. Your next question is coming from Michael Schmidt of Guggenheim Securities. Michael, please ask your question.
spk16: Hey, this is Kelsey on for Michael. Thanks for taking our question. I guess first, how do you think about the evolving post-CAR-T landscape now that we're starting to see filings for the bispecific antibodies, which have shown pretty compelling post-CAR-T activity? And then maybe building upon that last question, I guess, as you continue evaluating the higher cell dose as well as multiple cycles for 596, I guess, what gives you confidence that you'll have enough data with enough follow-up by your end to determine if this is the go-forward asset? Thank you.
spk08: Yeah, absolutely. I think your first question, I think, is directly on point. Absolutely. I think whether it be lymphoma, post-card T cell, or more broadly, obviously, it's a dynamic landscape. And so when we've looked at the data that's certainly public around the T cell engagers, it's very encouraging, especially to what is out there today where there really is no standard of care and response rates are probably in the teens, progression-free survival is measured in a couple months. So I do think the T cell engagers are potentially absolutely a step forward there in that setting. And I think, you know, when we think about target product profile, we're certainly keeping the T cell engagers in mind, whether that be in late line patients or actually in earlier line patients where we also expect the T cell engagers to make inroads. I think given this patient population, to be clear, I think the durability of response given what is I don't want to say standard of care today, what is used today, as I mentioned, most patients you can measure progression-free survival in two to three months and overall survival in five to six months. So I don't necessarily think we need a tremendous amount of long-term durability data to understand whether we're having an impact with respect to durability of response in these late-line patients, post-card two.
spk01: Great, thanks. And then maybe the second one.
spk07: Sorry, what was your second question? I apologize.
spk16: Yeah, that's okay. I had a long question. I guess just kind of, you know, as 596 continues to progress and you're evaluating the higher cell dose and the multiple cycles, I guess what kind of gives you the confidence that you'll have enough data with enough follow-up by your end to kind of make that go-forward decision? with one or the other?
spk08: Yeah, so, I mean, I think we should continue to subscribe to the fact that, especially in aggressive lymphoma, that responses happen quickly. There's a lot of data sets, obviously, to document that in autologous CAR T cell land. We certainly have data from our investigators, and we have, obviously, our own data sets to suggest and continue to reinforce that response has happened quickly. So I think we don't necessarily have to have long-term durability to determine whether or not we think the assets are meeting the appropriate target product profile to ultimately be highly competitive.
spk16: Got it. Okay.
spk09: Thank you so much, Scott. Sure. Thank you. Your next question is coming from Tyler Van Buren of Cowan. Tyler, please ask your question.
spk11: Hey, guys. Good afternoon, and thanks very much for the update. As we think about the update at the year end with FD516 and 596, can you give us a sense of how many patients will have 12 months of follow-up by the ASH cutoff? And when we think about potential denominator for assessing 12-month CR rate, And what do you believe is the minimum bar to be competitive with autologous CAR T and by specifics? And do you think this will be a relatively definitive observation of long-term durability for your platform, which I guess you just answered to some extent?
spk08: Yeah, I mean, there's five questions in there. I mean, at some basic level, we do not necessarily expect that we're going to have long-term durability data on the high-dose cohorts. given that we're just initiating at 1.8 billion cells, whether that be one dose, two dose, or three doses. So relatively speaking, at the high dose cohorts, we think the data will still be emerging at those higher doses. How we compete with T cell engagers or CAR T cell therapy, I think it really depends on the setting. I don't think patient-derived CAR T cell therapy is a line of therapy post-CAR T. So I don't think that is something you're competing with post CAR T. T cell engagers, absolutely. I think T cell engagers will be used post CAR T. So I think that is a force of competition. In terms of earlier Lyme usage, I do not believe that autologous CAR T cell therapy or even cell therapies that significantly rely on CyFlu will be broadly utilized in early Lyme therapy in the community. Although, again, once again, I do think T cell engagers will be used there. So I think in the earlier line settings, I think T cell engagers are a competitive force. At Memorial Sloan Kettering's and MD Anderson's, absolutely, autologous scar T cell therapy is a bar. That said, I believe there still continues to be at, for instance, those specialized centers, a significant number of patients that do not receive autologous CAR T cell therapies for a number of reasons. And that, I do think, provides an opportunity, even at those specialized centers, for folks developing allogeneic and off-the-shelf solutions.
spk01: Okay, I think that might be Tyler's questions answered. Is that okay?
spk07: Yep, that question, please.
spk09: Brilliant, thank you. Your next question is coming from Yigal Nachobobitz from Citigroup. Nigal, over to you.
spk04: Hi, Kim. This is Ashok Mubarak. I'm for Yigal. Thanks for taking my questions. I guess maybe thinking about this from a slightly broader perspective, with Brianzi and Escarta now moving into the second line in BCL, given the success of the Transform and Zuma trials. Does that change your thinking in terms of the commercial strategy? Of course, we know you're starting with the post-CV19 CAR-T setting, but as you're thinking about the frontline setting, do you maybe think at some point as the CAR-Ts move higher that you'll have to do some type of head-to-head study with the CAR-Ts with either 516 or 596?
spk08: I think longer term, certainly that's a possibility. So I do think, quite honestly... While there was a study certainly run in a second line setting, I continue to believe that post-card T cell therapy will have substantial challenges moving into the second line in the community setting. And so as we think about the landscape, we tend to think about it in three buckets. We tend to think about the community setting, we tend to think about the specialized centers, and we tend to think about patients that are very late line post-card T cell therapy. I think, you know, as I sort of just discussed, I think post-CD19 CAR T cell therapy, I think the landscape, you know, patient outcomes are fairly dismal, although, again, I think we've just recently seen T cell engagers show some promising responses post-CAR T. I think in the early line settings, I continue to believe that the Standard chemo immunotherapy regimens that are used and have been used over the course of years will continue to be the backbone in treating patients early in the community setting. And our strategy is to simply add a cell therapy without CyFlu onto those regimens. And we believe that that is a winning strategy compared to CyFlu plus CAR-T.
spk04: Okay. Got it. And then maybe, maybe one follow up. I know you'll be speaking with the FDA later this quarter, but, but is your sense that you still, um, is your sense that you'll still need to just conduct a single arm study in, uh, the cell lymphoma, uh, for proceeding 19 CAR T setting, or do you think that, uh, that is still really open to debate?
spk08: Uh, well, we'll certainly know that with more, uh, more definitive view, um, in the next couple months, I believe if I look at the landscape generally, of late-line cancer salvage setting, I do believe that the FDA will be open, albeit it may be an accelerated approval, I do believe the FDA will be open to a single-arm study.
spk00: Okay, got it.
spk01: Thank you very much. Sure.
spk09: Thank you. Your next question is coming from Michael Yee of Jefferies. Michael, please ask your question.
spk13: Hey, thanks. Good afternoon. Hey, Scott. I guess pivoting away from lymphoma for a moment, can you just remind us, since it sounds like you will give an update on solid tumors around CITC, whether that would be mostly 538 with the ongoing three antibodies and how to put that into context? And it feels like 536, MYC-AB is just early, so I presume nothing there. So maybe just talk a little bit about 538 or what we would get there. And then with myeloma, you could understand that huge market and certainly similar to post-CAR-CD19, you know, there's a post-BCMA market. So with 538 and 576 ongoing, how do you think about what's needed there given that BCMA is a bar but maybe also just post-BCMA? And would we have data there to give us some picture at the end of the year? Thanks.
spk08: Sure. Yeah, I think I'll take your last question first. I think the multiple myeloma market and our strategy will be very similar to what has played out so far in lymphoma. So with both 538 and 576, I mean, certainly we are getting patients that have been previously treated with BCMA-targeted therapies. And I do believe there will be an opportunity to rapidly advance a product candidate You know, towards or in a registrational pathway where you are treating patients that, for instance, are post CAR T cell therapy, DCMA targeted therapy. Very similar to, for instance, the strategy in lymphoma post CD19 for T cell therapy. So I think that opportunity will exist. Again, I do think, you know, our strategy, again, will be very similar. We will look to take, for instance, FT576. Given that it can combine, it's designed to combine with daratumab, which is used early and often, we do believe there are some foundational synergies with daratumab that we will be able to move this product candidate into early-line therapy and treat patients in the community. Where CAR-T cell therapy, understanding there's been studies run, certainly may have difficult, in actuality, reaching large numbers of patients. So I think the multiple myeloma strategy will play out very similarly to lymphoma, just in terms of how we're seeing the landscape today. In terms of CITC, I think we are going to take the opportunity to showcase the solid tumor franchise broadly. That will certainly include clinical data with 538, albeit early. We're still at, you know, earlier in dose escalation. with FT536 to the extent, you know, we have early clinical data. I'm actually happy to talk about early clinical data with FT536. It's a very novel product, novel targeting strategy. And we will certainly take the opportunity to discuss innovation as well as collaboration product candidates that are emerging. So I expect us at CICI to give a sort of a full update on our solid chamber franchises, which will include clinical as well as preclinical. as well as collaboration candidates that are emerging.
spk13: Perfect. And just to clarify your comment on myeloma, BCMA does set a high bar in the later line. So if you do have patients post-BCMA, similar to what we're talking about in lymphoma, if you see CRs there or PRs, that would be compelling to you?
spk08: Yeah, absolutely. And this is why I think FT576, like FT596, is differentiated, right? At some basic level, we have built products in lymphoma and myeloma that are designed to synergize with monoclonal antibody therapy. And they're designed to enable multi-antigen targeting. And with respect to 20 in lymphoma and certainly CD38 in myeloma, they tend to be more durably expressed targets as well.
spk09: Thanks. Thank you very much. Your next question is coming from Peter Lawson of Barclays. Peter, please ask your question.
spk02: Hi, this is Cheyenne from Peter. Thanks for taking the question. Ahead of the ASH update that you've mentioned, should we still be thinking that there's an update around the summertime, such as August for 516 and 596? And would you be including an update on the outcomes for the RMAT meeting at this time, or would it be too soon? And I just have a quick follow-up after that.
spk08: It would be very difficult for us to provide an RMAT discussion in August. The meeting, I think, is scheduled for the third quarter. We will certainly wait for minutes to come back from the FDA before having and fully digesting the update of that regulatory discussion. I think our plans are to provide, at this point, is to provide a comprehensive update on our development strategy in lymphoma with respect to our NK cells. And to provide a comprehensive update, we certainly would like the regulatory feedback. We're expecting to get, obviously, data at higher dose levels in three-dose cohorts and on the manufacturing pillar being in a position to have launched production of a pivotal product. So I think, you know, we're looking to do a comprehensive update. We won't do it in August. But certainly looking to do that within the next six months.
spk02: Okay, understood. Some more comprehensive picture maybe around ASH update timeframe. And then given that the on that meeting is N3Q, how should we be thinking of whether the pivotal study and post CAR T patients potentially could start by year end? Or should we be thinking that's more likely a first half event? And is 596 still on the table along with 516?
spk08: Yeah, so I think, you know, we're going to continue. We'll have the discussion with the FDA with respect to the franchise. We'll continue to generate more data with 516 and 596. We'll obviously be able to be in a position to make a decision on a product candidate. I suspect the product candidate we will be advancing will be a multi-antigen targeted product candidate, i.e. FT596, as we think that has broad applicability throughout the lines of care in lymphoma.
spk02: Okay, great. That's helpful, Tyler. Thank you. And so I imagine there's PAN dialogue with the FDA around 596 beyond this RMAT meeting for 596.
spk08: To be fair, most of the conversation agenda discussion points are agnostic to product content.
spk02: Okay, that's fair.
spk09: Thank you. I appreciate it.
spk00: Sure.
spk09: Thank you. Your next question is coming from Nick Abbott of Wells Fargo. Nick, please ask your question.
spk05: Hey, guys. This is James. Just two quick ones from our end. Will there be an update for 538 AML program on top of the solar treatment program by the end of this year? And then, number two, I'm not sure how much you can say about the shoreline lawsuit, but is there any idea when this could be resolved or when we could hear an update?
spk08: The last question is easy. I'm not going to comment on... intellectual property litigation, other than to say we believe we have foundational intellectual property related to iPS cell technology that can be broadly applied in the field and more specifically to NK cell and T cell cancer immunotherapy. With respect to FT538 and AML, We are dosing at the highest dose level. It is currently allowed under the protocol at 1.5 billion cells, multiple doses, three doses in a cycle. And yes, we believe we will be in a position to provide an update on FT538 in relapsed refractory AML ash.
spk01: Thank you, guys. Sure.
spk09: Thank you. Your next question is coming from Matt Begler from Oppenheimer. Matt, please ask your question.
spk12: Hey Scott, thanks for the color. Just a question on the CAR T failure treatment setting. It sounds like you're defining it as both relapse and or refractory. I know we've seen really good remissions induced in the relapse setting, but can you just kind of remind us where we're at with refractory? Have we seen any efficacy there? Thanks.
spk08: So, I think the data that we've reported to date in the patients that are more refractory, we have seen less success than the patients that, for instance, have previously responded. I think it's still relatively speaking smaller data sets where we would make a clear distinction between relapse versus refractory. Obviously, most of our data sets to date that we've disclosed publicly have been at lower doses and using only a single-dose regimen. Obviously, we're now getting to the point where we're at higher doses, multi-dose regimens, and significantly increasing the cell load during the first two weeks.
spk12: Got it.
spk08: So it asks probably... I think it would be premature today for us to, for instance, solely select patients that are relapsed.
spk12: Gotcha. Okay. Makes sense. Thanks.
spk09: Thank you. Your next question is coming from Dana Graybosh from SVB Securities. Dana, please ask your question.
spk15: Hi. Thank you for the questions. First one, two questions. One on R-CHOP. I wonder if you can talk about the unique biological impact of CHOP chemotherapy versus CyFlu and why you think it could be a good conditioning regimen for FT-596 in particular versus other cell therapies? And the second question on that is why go with one dose of FT-596 with R-CHOP before you get all the data for the multiple doses in the relapsed refractory setting?
spk08: Okay. So I'll let Wayne chime in when I miss some stuff, which I will. So the last question, let me just clear up any confusion. So as you know, a CHOP cycle, is 21 days, right? And so we are giving a single dose within each cycle. And so, you know, for instance, CHOP is delivered over typically the first five days in a cycle. And then we will add on FT-596 probably three or four days after that. So think about day eight to day 10. We are moving into frontline patients. And in all seriousness, I think it is prudent for us in these frontline patients to start with a single dose for each cycle. That does not mean that we can't increase cellular load either through dose escalation or multiple doses in ARCHA. But given the frontline patients and given the history of these patients, I think starting out with a single dose in a cycle does make sense. And keep in mind, we have historically seen to date even at lower doses, single dose, a persistence profile of FT596 of approximately 14 days, which fits very nicely, so a single dose would fit very nicely into a 21-day cycle as an example. With respect to our CHOP, you know, I think this is the interesting thing about this. We don't know. Cell therapy has historically relied on side flu as a conditioning regimen. The biological sort of mechanism of action in CyFlu, I think, is probably multifactorial. I tend to think it has to do with a cytokine spike that potentiates cells and reduces the competitive forces that come from the patient's immune cells for those cytokines. With respect to R-CHOP, I think the question is going to be, is that cytokine spike with R-CHOP comparable to PSYFLU. And I think we'll be able to get a very good sense of that very early on with respect to the translational data. Keep in mind, one benefit and unique benefit of FT-596 compared to any other cell therapies that have potentially tried to do this in the past, and I can't think of one off the top of my head, FT-596 has the benefit of twofold. Number one, It has IL-15 receptor fusion, so it has its own fueling mechanism such that it is less dependent on side flow. And number two, it's designed to synergize with rituximab, which obviously will act as a potentiating signal as well.
spk07: Wayne, do you have any comments on RCHOP versus?
spk05: No, other than, you know, I think it's an important question to address. which is why we feel it's an important study to conduct. And even with flu Cy, I would just point out that there's a lot of heterogeneity with respect to the doses of flu and Cy, even in the multiply relapsed through factory setting. So I think the main question we want to address is, are other chemotherapy regimens such as CHOP sufficient to support INK function and persistence? And that's what we aim to do in this study.
spk08: And I think, you know, there is not necessarily with R-CHOP do I think it's been demonstrated, but I think with, for instance, bendamustine, I think it's been clearly demonstrated that you can replace, for instance, CyFlu with bendamustine in lymphoma. There's a lot of data out there, and there's data that I'm aware of that I don't believe is published yet, but is going to reinforce that, for instance, bendamustine can be used very effectively instead of CyFlu.
spk15: Great, thank you.
spk08: I think the potential to plug in to standard immunochemotherapy regimens in early line in the community setting, I think is where the field of cell therapy needs to drive.
spk01: Thank you.
spk09: Your next question is coming from Robin Karmouskas from Truist Securities. Robin, please ask your question.
spk10: Hi. Hi, Scott. Thanks for taking my question. I just have a few, and these are really simple clarifications. So just regarding data readout, you said you want to have a comprehensive data readout in the next six months. But I think you also said we'll have data at ASH. Can you just give more clarity? Are we for sure going to have data, I think, on 596 at least at higher doses, like 900 million, maybe not the top dose at ASH? Or are you thinking that potentially plus some data and then a more comprehensive readout a little bit later. I'm just trying to understand the cadence of data.
spk08: It's really easy. Our goal is to provide a comprehensive update, whether that takes place at ASH as part of the formal ASH conference, whether that takes place at an investor event at ASH, or whether that takes place, for instance, in January. We want to provide a comprehensive update across the program. And that one includes both the regulatory, manufacturing, and clinical pillars.
spk10: Great.
spk08: And then my second question is... I believe that will happen in the next six months.
spk10: Okay. And then you are having your RMAP meeting this quarter. Would you still be on track for starting a trial by the end of the year, or could that be pushed out to early next year?
spk08: Certainly going to depend on an RMAC discussion. Okay. And then the last question is... And what kind of feedback we get from the FDA with respect to our proposed design of a study. But I do think, at least from a manufacturing perspective, we'll be well positioned to produce pithol material. The regulatory strategy will come into clarity within the next couple months. And obviously the clinical data will be further elucidated in the next couple months.
spk10: Got it. That's really helpful. And then the last question is more broad. So you showed the preclinical data, ACR and ADR. With the trend toward delivering a more potent burst of cell therapy to get around and getting around flu-sci, is ADR enough or do you have to do more things to create that super first dose, high dose trend? or high response rate on first dose with cell therapy. So I guess the bigger question, is ADR enough, or what else do you think we need to see or do to actually get your cells at that high potency?
spk08: Yeah, well, to be clear, I mean, we're investing in innovation. So as an example, we just had a discussion around FT596 plus ARCSHOP. Again, we have to run the experiment. ARCSHOP may be sufficient in potentiating FT596. We have to run that experiment. That said, we want to continue investing in innovation. I do think with an NK cell, the trick with NK cells or the mission with NK cells is to continue to focus on the potentiation signals that essentially induce activity on these cells. I also think as we've been having a conversation obviously, continuing to reduce or eliminate the dependency on psy flu is going to be absolutely critical to broad patient utilization whether that's lymphoma myeloma and solid tumors and so i think you know as we think about continuing to innovate a technology for instance or an approach like adr where we think that cells can be absolutely potentiated by leveraging an intact immune system is highly differentiating, very unique, and that technology, if successful, would allow cell therapies to be used early and often in treating patients, whether that be lymphoma, myeloma, or cell retention.
spk15: Great. Thanks, Scott.
spk01: Sure.
spk09: Thank you. Your next question is coming from Mara Goldstein from Mizzou. Mara, please ask your question.
spk14: Hi, this is support for Mara. I have a question on Ahmed, on the Ahmed meeting. Will you also discuss the CMC aspect of the products in addition to the clinical discussion? And also, obviously, depending on the outcome of the meeting and the possibility of the trial start, do you anticipate a change to the thoughts about cash for 2023? and have a follow-up?
spk08: So the RMAT discussion that we're having in the third quarter will include some CMC topics, but one of the benefits of RMAT is that you can frequently engage the FDA. So we may be in a position where we would like to have a rapid follow-on meeting with the FDA, to, for instance, delve more deeply into, for instance, some of the CMC questions. I would say generally speaking, yes, there are absolutely some CMC questions that we want to delve into. So, for instance, potency assay is something that frequently comes up in the world of cell therapies. That said, Keep in mind, we've been working with the FDA over the past three years on CMC manufacturer of IPS-derived cell therapy. And so over the course of the past three years, we've had lots of interaction, quite frankly, with the FDA on CMC. And we actually believe we're in a pretty good position with respect to CMC for IPS-derived NK and T cell product candidates, given the interaction over the past three years and the multiple INDs that we have cleared during and over that period of time. With respect to burn, our current burn and projections obviously do assume we're advancing into pivotal studies.
spk14: Got it. My second question is on the multiple myeloma study, and it was touched on a little bit earlier, but I'm just curious for the study of 576, particularly the combo with Dara, what studies or what agents should be used as a benchmark? Should we think of it in terms of comparing it to the bispecific, for example? Can you add some clarity on that?
spk07: Yeah, again, I say this a lot.
spk08: I think the comparator depends on the setting. So I think that's what matters at the end of the day. It's what line of therapy you're in, What setting of intervention? Are you in an academic center? Are you in a patient, in a community setting? Are you down line of a therapy that has failed? I think all of that matters. We're early in dose escalation. We're looking for activity in synergy with daratumumab. Activity of the CAR in synergy with daratumumab.
spk14: And lastly, At Ashley CA, do you anticipate to have some kind of in-person COVID meeting, or is it just purely at the conference?
spk07: That's TBD.
spk14: TBD, okay, got it. Thank you so much.
spk09: Okay, we don't appear to have any further questions in the queue. I will now hum back for any closing remarks.
spk08: Perfect. Thank you, everyone, for your participation today. Appreciate all the great questions. Be following up very soon.
spk07: Be well.
spk09: Thank you, ladies and gentlemen. This does conclude today's conference call. You may disconnect your phone lines at this time and have a wonderful day. Thank you for your participation.
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