This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk09: Welcome to the FATE Therapeutics first quarter 2022 financial results conference call. At this time, all participants are in listen-only mode. This call is being webcasted live on the investor's section of FATE's website at fatetherapeutics.com. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. As a reminder, today's call is being recorded. I would now like to introduce Scott Walshco, President and CEO of Fate Therapeutics.
spk02: Scott Walshco Thank you. Good afternoon, and thanks, everyone, for joining us for the Fate Therapeutics First Quarter 2022 Financial Results Call. Shortly after 4 p.m. Eastern Time today, we issued a press release with these results, which can be found on the Investors section of our website under Press Releases. In addition, Our Form 10-Q for the quarter ended March 31, 2022 was filed shortly thereafter and can be found on the investor section of our website under financial information. Before we begin, I would 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 the market today, as well as the risk factors included in our Form 10-Q for the quarter ended March 31, 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, state 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 Chiu, our Chief Medical Officer, Ed Dulock, our Chief Financial Officer, and Dr. Bob Valimer, our Chief Research and Development Officer. Today, we will highlight the clinical progress we have made during the first few months of 2022 with our off-the-shelf iPSC-derived NK and T-cell programs for the treatment of cancer. as well as note several key milestones that we are striving to achieve over the next several months across our four disease franchises. In addition, we continue to advance our collaborations with Janssen and Ohno with strong momentum, and we will discuss the upcoming milestones that we have the potential to achieve during 2022 under these collaborations. And finally, we will touch on our continued leadership in innovation, and highlight certain preclinical programs and data that we featured at the American Association for Cancer Research in April and that we plan to unveil at the American Society of Gene and Cell Therapy in May. I would like to begin today by highlighting our recent progress in advancing our off-the-shelf iPSC-derived NK and T cell programs for patients with hematologic malignancies and solid tumors. In the setting of B-cell lymphoma, we continue to enroll patients with relapsed refractory disease in our FT516 and FT596 Phase I studies. With respect to our FT516 program in combination with rituximab, multiple disease-specific expansion cohorts are currently ongoing as we continue to assess a multi-dose, multi-cycle treatment schedule of three once-weekly doses at 900 million cells per dose. With respect to our FT596 program in combination with rituximab, based on the favorable safety profile we have observed in the single-dose multi-cycle cohort, I am pleased to announce that we have now dose escalated this single-dose multi-cycle cohort to 1.8 billion cells. In addition, we continue to enroll a two-dose multi-cycle cohort at 900 million cells per dose, with FT596 administered on days 1 and 15, and intend to dose escalate this two-dose multi-cycle cohort to 1.8 billion cells per dose. In addition, we are seeing investigator enthusiasm for our FT819 program, the first ever T-cell therapy manufactured from a clonal iPSC line to undergo clinical investigation. The clonal master iPSC line for FT819 is created from a single iPSC that has a novel CD19-targeted 1XX CAR construct integrated into the T-cell receptor alpha constant locus, ensuring complete biallelic disruption of T-cell receptor expression and promoting uniform CAR expression. We are pleased to announce that we have now dose escalated the single-dose cohort to 180 million cells from 90 million cells. We are continuing to backfill this single-dose cohort at 90 million cells, which cleared with no dose-limiting toxicities, and no FT819-related grade three or greater adverse events. In addition to the single-dose cohort, we are also enrolling a multi-dose cohort with FT819 administered on days one, three, and five, and the first patients have been treated in this multi-dose cohort at 30 million cells per dose. As we consider registrational pathways in relapsed refractory B-cell lymphoma, we continue to believe a critical unmet need exists for patients who have progressed on multiple lines of therapy, especially CD19-targeted CAR T-cell therapy. While autologous CD19-targeted CAR T-cell therapy has led to remarkable improvements in outcomes for relapsed refractory patients, it is important to remember that about 30% of patients are primary refractory to CAR T-cell therapy, and the majority of responding patients will ultimately experience disease progression. Under our FT516 RMAT designation, we plan to engage the FDA in the coming weeks and hold a multidisciplinary meeting to discuss our proposed pivotal study design in patients who have progressed or relapsed following prior treatment with FDA-approved CD19-targeted CAR T-cell therapy. Importantly, no standard therapies are available for these patients, and recent retrospective analyses of real-world data presented at the 2021 Annual Meeting of the American Society of Hematology demonstrate extremely poor treatment outcomes. with complete response rates of administered therapies ranging from 5 to 25 percent, and overall survival ranging from 5 to 7 months. Under our FT516 RMAC designation, we also plan to discuss with the FDA key CMC topics applicable to our first-of-kind IPSC product platforms. With the operational launch of our second GMP manufacturing facility scheduled for mid-2022, we believe we are well equipped with the in-house expertise and capabilities to fulfill CMC requirements that are necessary for pivotal trial conduct, BLA submission, and initial commercial launch. We continue to believe that the post-CAR T cell setting represents a potential fast market development pathway based on the critical unmet need, and we are working to launch a pivotal study, whether that be with FT516 or FT596, by the end of 2022 for patients with aggressive lymphomas previously treated with autologous CD19-targeted CAR T cell therapies. 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 delivery of off-the-shelf cell therapies in the community setting without side flu chemotherapy conditionings as an add-on to frontline immunochemotherapy regimens, has the potential to transform outcomes for many patients with cancer. To that end, over the past several months, we have worked with investigators and key opinion leaders on a clinical protocol that brings FT596 into the community setting as an add-on to ARCHA, the standard first-line immunochemotherapy for patients with aggressive lymphomas. The proposed treatment schema in patients with newly diagnosed aggressive lymphomas includes administering up to six doses of FT596 without CyFlu chemotherapy conditioning, with one dose of FT596 administered twice. with each of six standard cycles of ARCHA. In the second quarter of 2022, we plan to submit the FT596 plus ARCHA protocol to the FT596 IND and expect to begin treating patients in the second half of 2022, subject to its allowance by the FDA. In the setting of multiple myeloma, We continue to enroll patients with relapsed refractory disease in the dose escalation stage of our FT538 and FT576 Phase 1 studies. With respect to our FT538 program in combination with daratumab, the multi-dose treatment schedule of three once-weekly doses at 100 million cells per dose, cleared with no dose-limiting toxicities, And enrollment is now ongoing at 300 million cells per dose. In addition, with respect to our FT576 program, the single-dose cohort as monotherapy at 100 million cells cleared with no dose left. And we have now treated the first patients in the single-dose cohort in combination with DAR2MAD at 100 million cells cleared. We are preparing to initiate multi-dose escalation cohorts with FT576 administered on days one and 15 as monotherapy and in combination with daratumum. In the setting of AML, the company's phase one study of FT538, which is designed to assess three once weekly doses of FT538 as monotherapy, in relapsed refractory patients is currently enrolling patients at one billion cells per dose. In addition, an investigator-initiated study of FT538 in combination with the CD38-targeted monoclonal antibody daratumab, which is designed to assess the therapeutic potential of targeting CD38-positive leukemic blasts, is also enrolling patients at one billion cells per dose. Both studies include the potential for further dose escalation. In the setting of solid tumors, I'm pleased to announce that we are poised to initiate a multicenter phase one clinical trial of FT536, the company's first iPSC-derived CAR and K-cell program for solid tumors. FT536 incorporates the company's high-affinity, non-cleavable CD16FC receptor to maximize antibody-dependent cellular cytotoxicity, as well as a CAR targeting the major histocompatibility complex class I-related proteins, MICA and MICB. High expression of MICA and MICB proteins, which is induced by cellular stress, damage, or transformation, has been reported on many solid tumors, although the protolytic shedding of the alpha-1 and alpha-2 domains of these proteins is recognized as a common tumor escape mechanism. The clonal master iPSC bank for FT536 was created from a single iPSC engineered with four functional elements, including the novel CAR, which uniquely targets the alpha-3 domain of MCA-MCB, and is designed to overcome tumor escape mechanisms mediated by loss of MHC Class I expression and protolytic shedding. We believe the product candidate's novel mechanisms of attack and ability to synergize with monoclonal antibody therapy can drive significantly improved outcomes for patients with solid tumors. We have successfully completed manufacture and are conducting final release testing of FT536. And we are working with the study's first clinical sites to initiate first patient enrollment by the end of May. The six-arm clinical study is designed to assess a multi-dose, multi-cycle treatment schedule of FT536 as monotherapy and in combination with monoclonal antibody therapy for advanced solid tumors. We look forward to providing clinical updates for our multiplexed engineered IPSC-derived NK and T-cell product candidates across our disease franchises in the second half of 2022. Turning to our collaborations with Janssen and Ono, we continue to show strong momentum in bringing multiplexed engineered IPS-derived CAR-NK and CAR T-cell product candidates to patients for the treatment of hematologic malignancies and solid tumors. Under our collaboration with Janssen, we have now initiated IND-enabling activities for two IPS-derived CAR and K-cell collaboration candidates. And we are actively working together with Janssen to prepare and submit IND applications for both of these candidates. For each of these collaboration candidates, Janssen maintains the option subject to its payment of an option fee prior to IND submission to initiate worldwide clinical development. We maintain the right in the U.S., alongside Janssen, to co-commercialize and share equally in profits and losses of each collaboration candidate. As a reminder, under our collaboration, Janssen has the right to designate and contribute novel binding domains targeting up to four tumor-associated antigens. Janssen has now designated and contributed novel binding domains targeting three antigens, and we have now successfully achieved preclinical milestones for collaboration candidates targeting all three antigens. Under our collaboration with Ono, Ono has contributed a novel binding domain targeting a solid tumor-associated antigen, and we have now initiated the generation of the master cell bank for a multiplexed engineered IPS-derived CAR-T cell collaboration candidate targeting the solid tumor-associated antigen. We are poised to initiate IND-enabling activities for this solid tumor CAR T-cell collaboration candidate during the third quarter of 2022, at which time ONO has the option, subject to its payment of an option fee, to exercise its rights for worldwide clinical development and commercialization, while we maintain the right to co-develop and co-commercialize the CAR T-cell collaboration candidate in the U.S. and Europe alongside Ono. We are very pleased with the success we have 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, and we are now poised to achieve significant milestones in connection with option exercise by Janssen and Ono over the course of the next three to six months. Turning to our continued leadership and innovation, we continue to invest in building a first-in-class pipeline of multiplexed engineered product candidates for solid tumors, including through the development and incorporation of new functional elements designed to overcome critical barriers that limit cell therapy, such as the requirement for patient lymphoconditioning, tumor antigen escape, and the immunosuppressive tumor microenvironment. At the American Association for Cancer Research in April, we presented our synthetic alloimmune defense receptor, or ADR, which targets 401BB upregulated on host alloreactive immune cells and is designed to eliminate the need for patient conditioning in administering off-the-shelf cell-based cancer immunotherapy. In preclinical models, we showed that ADR-armed, IPS-derived NK cells demonstrate enhanced functional persistence in vitro in the presence of alloreactive NK and T cells and exhibit durable antitumor activity in vivo in the presence of alloreactive T cells. These preclinical data provide proof of concept that ADR-armed cell therapies have the potential to persist and induce potent anti-tumor activity without requiring a patient to undergo chemotherapy conditioning to deplete the host immune system. In addition, we showcased our novel chimeric CD3 fusion receptor, or CD3FR. which is designed to enable off-the-shelf cell-based cancer immunotherapies to combine and synergize with CD3 bispecific engagers. In developing off-the-shelf CAR T-cell therapies, TCR expression must be eliminated to prevent graft-first host disease. However, the absence of TCR expression leads to loss of surface CD3 expression. Similarly, NK cells naturally lack TCR expression and have no surface CD3 expression. In preclinical models, we showed that CD3FR-armed IPS-derived CAR T cells, in combination with a bispecific engager, demonstrate target-specific cytotoxicity in vitro through CD3FR engagement, and enable dual antigen targeting. These preclinical data provide proof of concept that, much like our HNCD16FC receptor that enables synergy with monoclonal antibody therapy, our CD3FR enables armed IPS-derived CAR and K and CAR T cells to effectively combine and synergize with CD3 bispecific engagers for a multi-pronged attack on heterogeneous solid tumors. Later this month, at the American Society of Gene and Cell Therapy, we plan to present nine abstracts covering our proprietary IPSC product platform, including the unveiling of our most sophisticated multiplexed engineered IPS-derived cell product to date. we are currently developing an off-the-shelf IPS-derived CAR T-cell product candidate for solid tumors. That incorporates seven functional modalities, including three modes of tumor targeting to overcome tumor heterogeneity, as well as a novel synthetic CXCR2 homing receptor to promote trafficking to solid tumors, and a novel synthetic TGF-beta redirector receptor to promote activation in response to repressive signaling in the tumor microenvironment. While we will not yet disclose the CAR construct solid tumor target, preclinical data will show that the novel binding domain exhibits unique antigen recognition and tumor selectivity, with the ability to discriminate between antigen expressed on tumor cells versus normal tissue. We look forward to advancing our first off-the-shelf IPS-derived CAR T-cell product candidate for solid tumors into IMD-enabling activities later this year. I would now like to turn the call over to Ed to highlight our first quarter financial results.
spk01: Thank you, Scott, and good afternoon. Faith Therapeutics is in a strong financial position to advance our platform and pipeline. Our cash, cash equivalents, and investments at the end of the first quarter of 2022 were approximately $642 million. In the first quarter of this year, our collaboration revenue derived from our partnerships with Janssen and Ono Pharmaceutical increased by $7.3 million to $18.4 million. compared to $11.1 million for the same period last year. Research and development expenses for the first quarter increased by $27.3 million to $72.1 million, compared to $44.9 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 professional consultants. General and administrative expenses for the first quarter of 2022 increased by $8.2 million to $20.7 million, compared to $12.5 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 talent acquisition and facility-related fees. Total operating expenses for the first quarter were $92.9 million, which includes $19.2 million of non-cash share-based compensation expense. Note that, in connection with the development of our off-the-shelf IPSC-derived CAR T-cell product candidate FT819, we previously achieved the clinical milestone set forth in our amended license agreement with Memorial Sloan Kettering Cancer Center, which triggered 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 assessed the fair value of these contingent milestone payments, currently valued at $15.8 million on a quarterly basis. In the first quarter, we recorded a non-cash $8.4 million non-operating benefit associated with the change in fair value. Our net loss for the first quarter of the year was $65.7 million, or 68 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 Pharmaceuticals. I would now like to open the call up to questions.
spk09: As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Tyler Van Buren with Cowen. Tyler, your line is now open.
spk13: Hi, guys. This is Tara on for Tyler. I was just wondering if we can get an update on when we might expect initial data from the AML, multiple myeloma, and potentially from the solid tumor clinical programs this year? Thanks.
spk02: Yeah, I think in our prepared remarks, we made a statement that we plan on providing clinical updates across our four disease franchises in the second half of 2022. Okay.
spk13: Well, can I actually ask one more? So one thing that you mentioned last quarter was that for FT516 you were doing this R-BENDA combination, and I didn't hear you mention it here. So I was wondering if that was still in the plan. And for the FT596 plus RCHOP, will those patients that are now being treated, will they be included potentially in the August update or at ASH?
spk02: So I mentioned with respect to the FT516 study, there are multiple dose expansion cohorts ongoing in the FT516 study, which would include Arvenda. With the FT596 study, We are preparing the clinical protocol for FT596 plus RCHOP to submit to the FDA. And I mentioned, I believe, that we plan on beginning, subject to its clearance, we plan on beginning treating patients in the second half of 2022 with respect to FT596 plus RCHOP. Okay, thanks.
spk09: Our next question comes from Michael Yee of Jefferies. Michael, your line is now open.
spk04: Hey, Scott. Thank you for the update. Two questions for us. I thought your comments around 819, iPSC CAR-T were pretty interesting, and I guess you've started dosing patients. So, maybe you could talk a little bit about how we should expect the bar for you, given other peers out there. I know you'll have, maybe have some data at the end of this year. How should we think about that data in comparison to others in the bar set there, considering you're probably at low doses? And then second question is similar. In myeloma as well, there's obviously a bar out there for some pretty compelling drugs, particularly with CAR-T. You have a drug, I think, obviously with CD38 and BCMA. So maybe just talk a little bit about how we would expect that efficacy bar and whether patients would or would not have loss in BCMA and would that still work? et cetera, et cetera. Thank you.
spk02: Sure. So let me start with the myeloma, and then I can move to 819. So with myeloma, I think, again, it's early, but I'm not going to be surprised. I think I've said this before. I'm not going to be surprised if the strategy plays out similarly to how we're pursuing lymphoma, meaning that with FT576, we think, obviously, with its dual antigen targeting potential, it could potentially be used down the line of patients with who have received, for instance, CAR-T targeted BCMA therapy. And in fact, in our studies, both with respect to 538 as well as 576, I believe we have treated patients that are, in fact, have previous experience with the approved CAR-BCMA cell therapies. So, you know, obviously I have to look at the data. We're earlier on in myeloma compared to lymphoma. But I do think there potentially in myeloma will be a similar fast-to-market strategy that may emerge initially down the line of the FDA-approved CARB-BCMA therapies. It does not mean that's the totality of our development path. Obviously, we've developed product candidates that we believe can synergize with daratumab, and daratumab is used early and often throughout multiple lines of therapy. but I do think there will potentially be a fast-market strategy that evolves in myeloma much like lymphoma. And we're excited about those opportunities as a first opportunity, as a first chance to put a stake in the ground for our product candidates and begin to develop around that. With respect to 819, look, this is our first experience with an IPS-derived CAR T cell therapy. I mean, this has been long in development over the past, I think we entered into the collaboration with Memorial Sloan Kettering, back in 2016 to develop the first ever IPS-derived CAR T-cell therapy. We're here. We're treating patients. Interestingly enough, we started at 90 million cells per dose. And I think if you look at the approved CAR T-cell therapies in DLBCL patients, aggressive lymphomas, The dose that is often given to those patients is probably in the 100 to 200 million cell range. So in starting at 90 million cells per dose, I'm not suggesting by any means it's the most efficacious dose, but we are starting at a dose that if we truly do make essentially alpha-beta T cells, You know, we may be starting at dose levels that have the potential to show activity. Thank you. Sure.
spk09: Our next call, our next question is from Egal Notomovic with Citigroup. Egal, your line is now open.
spk07: Yeah. Hi, Scott and team. Thanks for taking the questions. I'm just wondering, with regard to the RMAC meeting that's coming up, could you just clarify as to why FT596 does not appear to be part of that discussion? I would have thought that, you know, FT596 would also be, you know, a useful option in the post-CD19 CAR-T setting for B-cell lymphoma. Thanks.
spk02: Sure. So to be clear and clear up any confusion, I absolutely believe FT-596 is applicable down the line of CAR T cell therapy, without a doubt. The RMAT designation is very specific for FT-516. So the meeting that we're planning is specific to FT-516. The RMAT designation was granted to FT-516. That said, many of the topics we will be covering whether it relates to clinical study design, endpoints, CMC, are applicable to FT-596. And so, what we plan on discussing with respect to the RMAT discussion with the upcoming RMAT discussion really is more agnostic to product candidate. What is the clinical study design? What are endpoints? We have a proposed study design that we would like to review with the FDA. There are CMC issues that are unique to iPS-derived cell therapies that we also plan on discussing with the FDA. So while this meeting is specific for 516, we do believe the output of that meeting will be highly applicable to FT-596. And ultimately, as we progress into the second half of 2022, we will make a decision with respect to FT-516 or FT-596 for conduct of the pivotal study.
spk07: Got it. Okay. That's super helpful. And then I just had a question on FT-596 plus rituximab and the new dosing regimens that you're rolling out. So just curious, you know, based on everything you know about 596, NK cell biology, and NK cell persistence, Just wondering, asking you to speculate, you know, which do you think would be more effective, the single-dose 1.8 billion or the multi-dose 900 million given twice? Which do you believe is likely to be superior, or do you think they could just end up being very similar? Thanks.
spk02: So I think I've always been on record saying that I think the right schedule for for treating patients with NK cells very likely includes multiple doses. And I still believe that today. So I do believe when delivering an NK cell, given their relatively short persistence compared to a T cell, and given they are significantly less prone to expand and proliferate as compared to a T cell, I fundamentally believe a multi-dose schedule for an NK cell is going to be the most efficacious path. And to be clear, we are delivering multiple doses at 900 million cells per dose. We're also delivering a single dose at 1.8 billion. Both pathways provide... enable us, the clearance of those pathways enable us to get to 1.8 billion times two, day one and day 15, and that's where we're headed.
spk07: Gotcha. Okay. And then if I could just throw in one more on myeloma. Sure. So obviously you've done a lot of great work building a cell therapy that can function in combination with Darzalex given the CD38 knockout. Just wondering if How much consideration have you guys given to potential combinations with other standard of care agents in myeloma, for instance, IMIDs or proteasome inhibitors?
spk02: We've done some preclinical work in assessing other combinations, but you are correct. I mean, the driver with respect to the therapeutic design is, of both FT538 or 576 was really about creating a cell type that could uniquely synergize with daratumumab, given the concern with respect to fratricide. Obviously, activated NK cells, activated T cells, expressed CD38, and so there was the potential for fratricide. We always thought there would be significant opportunity to synergize with Darzalex. We'd certainly done doing preclinical experiment to understand how our product candidate could plug into existing regimens that include Darzalex, which, as you've alluded to, includes some of these IMIDs as an example. And so we don't think – we haven't seen anything to suggest that those other agents that are part of combination therapies would be detrimental to cells in any way.
spk07: Understood. Thanks, Scott.
spk02: Sure. Sure.
spk09: Our next question is from Dana Graybosh of SBB Securities. Dana, you have the floor.
spk11: Hi. Thank you for the questions. I think a couple for me. One, you know, we're talking so much about dose, you know, 900 million, 1.8 billion cells. I wonder whether you could help put that into context. You know, how many NK cells are circulating in an average patient or healthy human? And how does that compare to, let's say, 900 or 1.8 billion cells?
spk02: Sure. Bob or Wayne, do you want to address that question? We're not in the same room, but either one of you?
spk03: Sure. I could start. We typically have somewhere between 1 to 2 billion. So we're here with each dose at those high doses are reconstituting the NK compartment of a normal patient.
spk11: Okay, that's an easy answer. Thank you very much. The second one for multiple myeloma, I wonder if you could talk a bit more about your binder for BCMA. I think you've called it avidity-like, and I wonder if you could talk about what gives you confidence that your binder will give the same effect as avidity that's been used successfully in the BCMA CAR T's.
spk02: Sure. I think, again, either Bob or Wayne, Bob, do you want to address that question as I think you're most familiar with the unique characteristics of our particular binder? Sure.
spk03: So the binder was well characterized in a molecular therapy article back in 2018 by Arm and Rem. And so there he shows that the affinity of the binder allows the preclinical studies to target cells that had less than 1,000 BCMA per cell. So he was able to target BCMA per cell in the 100 range. So that gave us confidence that this binder is going to be unique. We've compared it to the competitors where we have access to the sequence, and it does outperform. So Armin's initial work and some of our preclinical work suggests that this binder is going to be of higher quality, higher avidity, and hopefully gives us better results and outcome.
spk11: Great. Thank you very much.
spk09: Our next question is from Nick Abbott with Wells Fargo. Nick, your line is now open.
spk05: Sure, Nick. Thank you very much for taking my questions. I do like the apologies if maybe you address this. But maybe starting off with 5.6 and all that, you know, that IND was approved several years ago, and notwithstanding the fact you've had several INDs approved since, things like FDA getting more focused on So do you think there could be any weaknesses in the manufacture of 516, and any weaknesses you think might be there? Can they be addressed without affecting the timeline?
spk02: Sure. So it's a great question, and your point's well taken. Yes, we did make the FT-516. The FT-516 IND was cleared, gosh, I think back in 2019, if I'm remembering correctly. Look, I think certainly while it is an early generation product candidate, I think as you probably will appreciate, our manufacturing process is agnostic to the master cell line. So the methods we're using, for instance, to create FT596, or FT576, are really the same exact methods that we used to create FT516. So the manufacturing processes that we use today in taking a master cell bank and creating large quantities of NK cells really transcends the product tendons. And that's, you know, back to Yigal's question, this is why I think, you know, certainly while we're having a discussion around FT-516 with respect to RMAT, I think many of the questions that we are intending to ask speak to the platform.
spk05: Great. Thanks, Scott. And then on 516, I'm looking at the press release. I'm trying to pass the terms progressed or elapsed following prior FDA-approved CAR TDS. They almost seem synonyms to me, but I'm sure you've pulled over this press release. What is the difference between someone who's progressed or elapsed following prior CAR-T?
spk02: I don't have the press release in front of me. I can go back and look at it. But the idea in patients, these are in patients that have been previously treated that have progressed and they may not have had a response. or have relapsed following a response. That's the patient population we're targeting down the line of CAR-T.
spk05: But not those who are, so does that include patients then who are primary refractory?
spk02: It could include patients that are primary refractory. That is correct.
spk05: Okay, okay, perfect. That's what I wanted. And then just in terms of the RCHOP combo, these patients are going to be treated in the communities. that's where they're being treated today. So is this a study that you can do in a sort of true community setting as opposed to a kind of outpatient setting of NGH, for example?
spk02: Yes, I think we're pretty confident in that. I mean, I'll turn it over to Wayne, and he can talk about this a little bit more because he's done a lot of work here, working with the investigators and the KOLs that helped us develop the protocol.
spk06: Sure. Yeah, we've spoken quite a lot to investigators and key opinion leaders around the concept of this, which, you know, at its most basic form, it's essentially standard dose and schedule of RCHOP and then administration of FT596, you know, a certain period of time after each cycle of RCHOP. And, you know, and we've demonstrated with our phase one data of FT596 that from a safety perspective, you know, FT-596 at the doses we've treated to date is quite safe in the sense that, you know, very little in the way of cytokine release syndrome, no ICANNs, no GVHD. And so when we developed the protocol with, you know, in partnership with investigators, they were quite comfortable with the idea that, one, from a safety perspective, there doesn't seem to be anything that would be disqualifying in terms of starting the study. And then secondly, there is quite a degree of comfort that not only would they be able to get patients to be treated with this, but also treat these patients in a way that's, you know, reasonably convenient, i.e., you know, administering FT-596 in an outpatient setting. So we're very confident that we will be able to have quite robust enrollment into this trial.
spk05: Sorry, if I can just follow up on that. I mean, I can envision a situation where the patient gets the R-CHOP in the community oncology office, but it sounds like then you might be sending the patient to the local CAR-2 treatment center.
spk02: No. That's not what's complicated here.
spk05: Okay.
spk02: Okay. That's not what's complicated. This is community setting outpatient treatment.
spk05: Perfect. Thank you very much.
spk09: Our next question is from Michael Schmidt with Guggenheim. Michael, your line is now open. Hey, this is Kelsey on for Michael.
spk10: Thanks for taking our question. For 596 plus rituximab, I guess up to how many dose cycles can be administered? And can you just remind us what patients are eligible to receive additional cycles now that the protocol amendment, I think, is in place? And then just a quick follow-up on that, I guess there was some competitor CAR and K-cell data last week, and I think for them at least, you know, the data suggested that three doses per cycle was better than two doses. I guess is this something that you guys would consider looking at in your treatment schedules, or are you pretty set on two doses per cycle for 596 at this time? Thank you.
spk02: Sure, I guess I'll address the last question first. Yeah, I mean, we are giving two doses of FT-596 on day one and day 15. In addition, 576 being delivered on day one and 15. The reality is we've seen responses from single doses, right? So I think, and we've looked at a lot of translational data and feel very comfortable with the functional persistence profile extending for about two weeks. So we feel pretty comfortable with the two-dose schedule given what we've seen on the translational side and given the fact that we've seen responses with a single dose. That said, our protocols have a tremendous amount of flexibility in them. And we certainly have the opportunity to backfill patients into a three-dose cohort if we chose to do that. So we have a lot of flexibility under the existing protocols. I would say similarly with respect to cycles, The protocols are set up essentially as a first cycle, a second cycle, and then I think under the existing protocols, and Wayne, you can correct me if I'm wrong, I believe under the existing protocols, patients do have the ability to go on to additional cycles. I don't know, Wayne, you want to comment on the cycles?
spk06: Yeah, that's absolutely correct. Right now, because of the FDA allowing us to proceed directly to a second cycle, we consider an initial treatment course with FT596 as consisting up to two cycles. And then in addition to that, specifically in patients who have an initial response and then subsequently progress, we have the option for re-treatment of those patients as well.
spk10: Got it. Okay. Thank you so much.
spk09: Our next question is from Mara Goldstein with Mizuho. Mara, your line is now open.
spk08: Great. Thanks so much for taking the questions. Scott, I want to be respectful, obviously, of of trade secrets and the like, but maybe you can talk a little bit about the CMC and, you know, what would be considered from your viewpoint a positive outcome from FDA with respect to the upcoming meeting, and really maybe if you could just give us something to think about in terms of what are the types of questions that you might be asking. And then I just had a question on the 516 trial, and curious if the protocol allows for the individual assessment of relapsed patients versus refractory patients.
spk02: So can you just clarify the second question first? What do you mean specifically? Do we treat refractory patients, refractory to LAS therapy as opposed to relapse to LAS therapy? Is that the question, LAS therapy?
spk08: Right, and if you are able to look at the outcomes, you know, within those buckets of, you know, within those different subgroups or it's just a global subgroup relapse refractory.
spk02: Currently, the cohorts are relapsed refractory in the same cohort, but that doesn't mean we can't segregate that on a go-forward basis if we chose to do so and treated them as unique populations. We would certainly be able to do that on a go-forward basis. But currently, the cohorts are relapsed to LAS therapy as well as refractory to LAS therapy. Okay. CMC, gosh. I guess, and thank you for making a comment about respectful trade secrets. I think, you know, one of the elements that has hung up cell therapy companies in the past, as I think you're well aware, is oftentimes potency assays. So you may suspect that one of the things that we certainly want to get ahead of in conversation with the FDA is are, for instance, some of the potency assays that we've developed. And now you could say, for instance, whether it be CAR-19 or CAR-BCMA, gosh, you know, there may not be a lot of trade secrets or a lot of innovation with respect to those potency assays. But CD16 is a powerful mechanism here, and so we are suspecting, don't know, but suspecting that we will require a potency assay for CD16. And so that's certainly something as an example that we would want to discuss with the FDA. given the prevalence of CD16, that feature, the high affinity non-clinical CD16 receptor that we're using throughout our product candidates. Again, sort of hearkening back to the comments that I made that many of the questions we're gonna ask here are not just relevant for 516, but are relevant for 596 as well as our platform. I think the other thing that we wanna have a conversation with Efti about is obviously not necessarily potency assay, but there are a whole host of other release specifications that are relevant for cell therapies. And beginning to reach agreement on release specifications for the conduct of a pivotal study, I think, again, can apply universally to our product candidates.
spk08: Okay. And if I could just ask a question. I mean, clearly you have a lot of resources. You'll end this year with $400 million. I understand not including any types of milestones or whatnot. But, you know, given the pipeline that you have and the plans to go into additional, you know, bigger and potentially more complex studies, I mean, how do you think about financing post, you know, 2022? Sure.
spk02: Look, I think we have two terrific collaborations with Ono and J&J that can provide meaningful streams. Do I think they're going to offset the entire burn of the company? No, I don't. But I do think the Ono and J&J collaborations, we have strong momentum. We're seeing success. It's publicly out there, maybe not exactly with respect to timelines and milestones at each stage, but it's publicly out there. what the milestones can represent with respect to each and every product candidate. And currently I alluded to the fact that we think we have three product candidates emerging from the two collaborations. And I do think there's the room for the company to do more collaborations. And I think we are actively in discussions to engage in more collaborations.
spk08: All right. Thanks. I appreciate it. Sure.
spk09: Our next question is from Robin from Truist Security.
spk12: Hi, guys. Thanks for taking my question, and I could spend the whole day on your new technology. But let me just ask a few. So on the dose, there's another question on the competitor data. That data used very high doses of 1 to 1.5 billion cells multiple times in AML and TLDCL. I was just curious your thoughts on the read here. to your whole program in dosing that high? Like, does the cell type matter, like IPC versus, you know, just either a donor-derived or another form of an NK cell? Or does this tell you that high doses really might work the best, and you may have to get up to that 1 to 1.5 billion dose? The second question is, how high per dose will you go? And then I had a follow-up on the RMAT trial.
spk02: So I guess a couple things, and I will say with respect to dose, again, there's a lot of literature and obviously clinical experience with NK cells versus T cells. And let's just stick in the lymphoma space because it's the easiest to compare and contrast. In the lymphoma space, right, obviously with CAR T cells, in the approved CAR T cells, we've seen doses that are fairly modest compared to an NK cell. I mean, we've seen doses in the 100 to 200 million range. Single dose, 100 to 200 million cells with Yescarta is the recommended dose, is the dose that's used today. I mean, that's exceptionally low compared to NK cell and the history of donor-derived NK cell. If you look at the history of donor-derived NK cell therapy and you go back and you look at the history, my gosh, people are giving you know, not 900 million cells. They're giving like five, six, seven, eight billion cells. So, you know, back to Dana's question, I mean, the history of donor-derived NK cell therapy, in order to try and drive even modest efficacy, folks have been delivering a multiple of the NK cell compartment that actually just exists within your body, which... Obviously now, and we've always said, and others in the industry will say the same thing, gosh, you know, if you really want to make an NK cell efficacious, you're going to have to engineer in functional elements. And I think with those engineering in functional elements, whether it be a CAR or a CD16 receptor or what have you, I do think you'll see dose levels of NK cells, lower dose levels of NK cells, be more efficacious. But clearly... they are going to be at dose levels, I think, that are higher than T cells. And I think that gets back to a little bit of the nature of a T versus an NK. When a T cell gets activated, it is quite capable of undergoing significant expansion and proliferation, and they do persist longer compared to an NK cell, which is not going to significantly expand as a T cell would, and it is not going to functionally persist as long as a T cell persists. So I think we've always believed, and I think it's playing out, that the NK cell doses and schedules will be different than what you have typically seen with T cells. The good news, I would say, with respect to the NK cell community, while it may require high doses, while it may require multiple doses, safety profile I still think is significantly differentiated compared to a T cell.
spk12: And since you don't know how durable those responses are yet, would you dose higher, you know, than where you're at right now?
spk02: Yeah, absolutely. I mean, yeah, I mean, I think that's the feedback that we got at ASH at some basic level from our investigators. We don't know what the durability is of an NK cell versus a T cell. No one knows. I mean, really, that question has not been answered in the community yet. What's the durability of an NK cell? And so given the safety profile, yes, we absolutely, and, you know, we're at 1.8 billion cells. So we will continue to dose escalate. We think we certainly have a platform that allows for the delivery of high doses, if that's necessary, and multiple doses.
spk12: And then a follow-up question on the RMAT 516 meeting. Do you have a sense of, for your clinical trial, how far out you might have to follow patients? There's been a lot of discussion, you know, versus the early CAR T studies that you kind of knew, like within six months, that there was durability or deep response. Do you give any sense of that? And then, I'm sorry, squeeze this one in. For your ADR, how close to market are you? And then no more questions. Thanks.
spk02: Okay. So let me discuss the clinical trial design, obviously, with the FDA and discuss potential endpoints. I think, you know, again, I think the one thing I would point out is, at least in the post-part T cell patient population, You know, I had some remarks with respect to the benchmarks that are out there with respect to, you know, therapies that are being at least trying to be deployed by physicians today. And I think, you know, we made a remark that, you know, complete response rates are somewhere between 5% to 25%, and overall survival, overall survival, you know, is around six months. So I think you're potentially... looking at a very difficult to treat patient populations where outcomes for better or for worse are determined very quickly. With respect to ADR, we have a lot of preclinical data with ADRs. We have not necessarily decided yet what product candidate to incorporate ADR technology into. That said, we think ADR technology and the idea of chemotherapy-free conditioning and delivery of cell therapy is the direction the field must go. We absolutely believe that CyFlu long-term is a barrier to cell therapy's ultimate potential, and technologies will need to be developed and utilized to reduce the dependency and requirement on CyFlu. And I do think we are targeting a 2023 time period for the integration of ADR technology.
spk12: Great. Thank you.
spk02: Sure.
spk09: And at this time, I would now like to turn the conference back to Scott Walshcomb.
spk02: Thank you very much. I appreciate everyone's time this afternoon. Thank you all for participating. Be well and look forward to catching up soon.
spk09: This concludes today's conference call. Thank you for participating. You may now disconnect.
Disclaimer