Fate Therapeutics Inc. Q1 2023 Earnings Call
Speaker 1: Thank.
Speaker 2: Welcome to the Faith Therapy Rix First Quarter 2023 Financial Results Conference call. At this time, all participants are in a listen on the amount. This call is being webcast live on the Investors section of Faith website at FaithSerapeutics.com.
Speaker 2: As I reminder, today's call is being recorded. I would now like to introduce Scott Walshko, President and CEO of Faith TherapyRex.
Speaker 3: Thank you. Good afternoon and thanks everyone for joining us for the state therapeutics first quarter 2023 financial results call.
Speaker 3: 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.
Speaker 3: In addition, our form 102 for the quarter ended March 31, 2023 was filed shortly thereafter and can be found on the Investor section of our website under financial information.
Speaker 3: 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 public provision of the Private Security litigation reform Act of 1995.
Speaker 3: These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward looking statements.
Speaker 3: Please see the forward-looking statement disclaimer on the CREPIDI's earnings press release issued after the close of market today, as well as the risk factors included in our form 10Q for the quarter-ended March 31, 2023 that was filed with the SEC today.
Speaker 3: Under Reliance should not be placed on forward looking statements, which speak only as their date they are made as the faxing circumstances underlying these forward looking statements may change. Except as required by law, they therapeutic to explain any obligation to update these forward looking statements to reflect future information, events, or circumstances. Joining me on today's call are Dr. Lane Chu, our Chief Medical Officer.
Speaker 3: Ed D'Lac, our Chief Financial Officer, and Dr. Bob Balliner, our Chief Research and Development Officer.
Speaker 3: We will focus today's discussion on the impact of our strategic pipeline prioritization and corporate restructuring.
Speaker 3: including the unwinding of our collaboration with Chanson.
Speaker 3: In addition, we will highlight our sharp and clinical focus for FT576 BCMA targeted car and K cell program in multiple myeloma and our FT18 and CD19 targeted car T cell program in B cell malignancies. Finally, we will share a progress in advancing our T2023 program initiatives for off-the-shelf IPF-C derived car and K and car T cell product pipeline.
Speaker 3: including under our collaboration with Ono Pharmaceutical. The first quarter of 2023 was a challenging period of transition for the company. The quarter was marked by the termination of our collaboration with Janssen, where we completed an orderly wind down of all collaboration activities.
Speaker 3: This included discontinuing all research and pre-clinical development of collaboration timidates, helping on going GNP manufacturing campaigns, and support clinical development.
Speaker 3: and withdrawn in IMD applications that had been allowed by the FDA for first collaboration product.
Speaker 3: As of the first quarter's end, we were no longer incurring any costs, reconnection with the Janssen collaboration, and all amounts owed by Janssen to fate have now been fully paid.
Speaker 3: We also completed a strategic review of our IPFC derived NKSL and TSL programs. Electing to focus operations on our most innovative and differentiated car and KSL and Cortiso product candidates.
Speaker 3: with the potential to address large, undimect clinical needs. As a result, we decided to discontinue further development of our FTPI-16, FTPI-096, FTPI-38, and FTPI-36 in case I'll program.
Speaker 3: While we are committed to minimizing all operating costs across the disk engineering programs.
Speaker 3: As a consequence of the termination of our JANs in collaboration and our strategic pipeline prioritization, we significantly reduced our workforce. In early January , we reduced our head count by over 60% to approximately 220 employees.
Speaker 3: which we expect to remain flat at least through the remainder of 2023.
Speaker 3: In addition, we substantially curtailed our support of investigator initiated clinical studies and sharpen the scope of our sponsor to research agreements.
Speaker 3: Finally, we are working to reduce our overhead costs and consolidate our operations at our corporate headquarters.
Speaker 3: With the implementation of this re-structuring, we are well positioned to achieve sea milestones across our programs.
Speaker 3: with a cash runway that extends into the second half of 2025.
Speaker 3: Before we review our progress in advancing our Q2023 program initiatives.
Speaker 3: I would like to turn the call over to Ed to elaborate on our financial results for the first quarter of 2022.
Speaker 3: turn the call over to Ed to elaborate on our financial results for the first quarter of 2023. Thank you Scott and good afternoon.
Speaker 3: Kate Therapeutics is in a strong financial position to achieve key inflection points across its pipeline. Our cash, cash equivalents, and investments at the end of the first quarter were approximately $413 million.
Speaker 3: This amount did not include an additional $14 million in collaboration receivables.
Speaker 3: of which we received $12.5 million from Janssen in the second quarter. In the first quarter of this year, our revenue increased significantly to $59 million.
Speaker 3: compared to $18.4 million for the same period last year. Most of our revenue in the quarter, or $58.6 million, was derived from three non-recurring sources. $41.2 million in deferred revenue recognition related to our firm-former collaboration with Janssen.
Speaker 3: $11.1 million associated with chance in wind-down activities.
Speaker 3: and $6.2 million of R&D expense reimbursement under our ongoing collaboration with ONO related to the completion of pre-clinical activities for FTE-825.
Speaker 3: Research and development expenses for the quarter decreased by $6.5 million to $65.6 million. The decrease in our R&D expenses was attributable primarily to the termination of the Janssen collaboration.
Speaker 3: It decreased in share-based compensation expense and from lower demand for R&D supplies and materials. General and administrative expenses for the first quarter increased by $1.2 million to $21.9 million.
Speaker 3: as well as $11 million in non-cash share-based compensation expense. Note that in connection with the development of our off-the-shelf, IPFC derived CAR-T cell product candidate F-T-819. 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.
Speaker 3: Up to two additional milestone payments may be owed to MSK based on subsequent trading values for the company's common stock, ranging from $100 to $150 per share.
Speaker 3: We assess the fair value of these contingent milestone payments.
Speaker 3: currently valued at $2.1 million on a quarterly basis. In the first quarter, we recorded a non-cash $1.7 million non-operating benefit associated with the change in fair value. Our net loss for the first quarter was $18.9 million or 19 cents per share. As we consider the remainder of this year, I want to highlight a few important factors that change the profile of the company's TNL. First, the company's revenue will be derived almost exclusively from our collaboration with ONO.
Speaker 3: and specifically for research funding in connection with the development of a second product candidate against an undisclosed target in solid tumors.
Speaker 3: We expect this amount to total about $800,000 per quarter through the third quarter of 2024. Second, as a result of our decision in the fourth quarter of last year to opt into a co-development and co-commercialization arrangement with ONO for FTA25 in the US and Europe .
Speaker 3: O'Known's portion of the program's expenses to be reimbursed to fate, which were previously captured as revenue, will now be recognized as an offset to our research and development expense.
Speaker 3: Third, while the company did implement its restructuring in the first quarter, we expect the cost reductions and additional operating leverage to begin to materialize in the second quarter.
Speaker 3: with additional benefits to accrue throughout the year as we complete the wind down of our discontinued programs.
Speaker 3: Finally, we expect our Gap operating expenses for the full year to be between $265 and $285 million.
Speaker 3: and that we will end the year with more than $300 million in cash and investments. I would now like to turn the call back over to Scott to discuss our key 2023 program initiatives. Thanks Ed. After staring down some significant challenges in the first quarter of 2023, we have emerged with a renewed sense of energy, commitment and drive.
Speaker 3: controls of cell function, deliver multiple mechanisms of action to maximize clinical efficacy, and maintain a safety profile that permits broad accessibility to patients, including in a community-based setting. In the first few months of this year, we have made great strides.
Speaker 3: and position the company to reach key inflection points across our programs.
Speaker 3: The treatment landscape for multiple myeloma remains highly fragmented, with the vast majority of patients receiving multiple lines of combination regimens in community-based settings throughout the course of treatment.
Speaker 3: FT576 is our off-the-shelf, GCMA-targeted, CARi-K cell program from hoploma myeloma that is uniquely designed to be administered with CD38-targeted monoclonal antibody therapy, which is widely used in combination regimens across lines of therapy.
Speaker 3: These are the off-the-shelf combination of F-T576 and CV-38 targeted monoclonal antibody therapy. They offer an attractive and differentiated therapeutic proposition.
Speaker 3: by enabling antibody-dependent cellular cytotoxicity, multi-antigen targeting with myeloma cells, and patient-reached inter-community base settings.
Speaker 3: We have previously reported internally phase one clinical data of the combination from the first single-bose treatment cohort at 100 million cells, which showed a favorable safety profile and clinical activity.
Speaker 3: Additionally, translational data from the cohort indicated rapid and selective depletion of activated C38-positive hosted immune cells through the first month of therapy, suggesting that the combination may create a favourable immune reconstitution profile.
Speaker 3: to extend F-T-576 functional persistence. As we continue to accruate patients in the dose escalation stage of our phase one study, we have prioritized enrollment of F-T-576 in combination with CD-38 targeted monoclonal antibody therapy. We are currently enrolling a two-dose treatment cohort.
Speaker 3: at 300 million cells per dose. And upon clearance, we expect to open and assess a three-dose treatment cohort at one billion cells per dose.
Speaker 3: In the area of B-cell lymphoma, where autologous CAR T-cell therapy has shown remarkable efficacy.
Speaker 3: The vast majority of patients do not receive a polygous car teeth self-arbitant for numerous reasons. Whether due to logistical barriers, disease aggressiveness requiring immediate intervention, or inability to combine with standard of care and miscellaneous therapies that are commonly administered in community-based settings. The vast majority of patients are not received, or inability to combine with standard of care and miscellaneous therapies that are commonly administered in community-based settings.
Speaker 3: FT522 is our office shelf CD19 targeted Coring Case Health Program for B. Solem FOMA that incorporates five novel synthetic controls of cell function.
Speaker 3: designed to increase NK cell potency, enhance functional persistence, and reduce or eliminate the need to administer intense conditioning chemotherapy to patients.
Speaker 3: Notably, FT-522 is the first product candidate to incorporate our proprietary alloimmune defense receptor or ADR technology which is designed to target 4,1-BB expressing post-immune cells and induce NK cell activation. We have previously presented preclinical data.
Speaker 3: demonstrating that ADR-armed IPS-derived CAR and K cells exhibit potent anti-tumor activity in the presence of alloreactive T cells.
Speaker 3: And we believe there is a significant opportunity for FQ-522 to be seamlessly combined with standard of care immunotherapies widely used in community-based settings.
Speaker 4: including for the treatment patients with newly diagnosed disease.
Speaker 4: I am pleased to announce that we have recently submitted an investigational new drug application to the FDA to initiate clinical investigation of FT-522.
Speaker 4: The proposed clinical schema is designed to assess a three-dose treatment schedule.
Speaker 4: In combination with CD-targeted monoclonal antibody therapy, including without administration of intensive conditioning chemotherapy to patients.
Speaker 4: We believe we are well positioned to initiate patient enrollment at a therapeutically relevant dose and dose schedule in the second half of 2023.
Speaker 4: We also continue to accrue patients into our landmark phase 1 study of FT819.
Speaker 4: are off the shelf, ITSC derived CD19 targeted car TSO product candidate for decelmal marath??? Finally SBU Live
Speaker 4: FT819 incorporates several first-of-kind features, including the integration of a novel 1xx bar construct into the track locus.
Speaker 4: which is intended to promote uniform car expression, balance, keep cell activation and exhaustion, and prevent graphose hosting.
Speaker 4: We have previously reported interim phase 1 clinical data.
Speaker 4: which showed a favorable safety profile and demonstrated responses in heavily pretreated patients.
Speaker 4: including in patients who are not eligible for or who have previously failed autologous CD19 targeted CAR T cell therapy.
Speaker 4: The phase one study is currently involving patients in a single dose treatment cohort at 540 million cells in B-cell lymphoma.
Speaker 4: And we plan to initiate a dose expansion cohort in the middle of 2022.
Speaker 4: We also continue to enroll patients in a single dose treatment cohort at 180 million cells in chronic lymphocytic leukemia, a disease that remains in terrible and for which utilization of opalides, parts, and self-therapy is limited due to the inherent dysfunction within the patient's immune system.
Speaker 4: We're excited to expand our IPSC-derived CAR T-cell product platform to solid tumors, where effective therapeutic solutions may need to address cell trafficking, the immunosuppressive tumor microenvironment, and tumor heterogeneity.
Speaker 4: We believe our multiplex for IPS derived Carti Cell product platform is designed specifically overcome these challenges.
Speaker 4: and enable the safe and effective treatment of solid tumors. Under our collaboration with ONO, we are currently conducting an I&B enabling activities for FTA-825-ONO-8250.
Speaker 4: A multi-flexed engineer, IPFC-derived, CAR-2 cell product candidate, targeting human at the Bureau of Growth, Factor 2, or HER2, expressed in solid tumors. The product candidate equates seven novel synthetic controls.
Speaker 4: designs to enhance effector cell function, including by promoting cell trafficking to the tumor site, redirecting immunosuppressive signals in the tumor microenvironment, and supporting T cell activation without eliciting exhaustion.
Speaker 4: In addition, we are currently engaged with the Ono Clinical Development Team and are jointly developing our clinical strategy for FQ825 Ono 8250.
Speaker 4: We remain on track to submit an IND application for FTA-25008250 in the second half of 2020 degrees.
Speaker 4: Finally, I'm excited to report that we have engaged multiple key opinion leaders and investigators who have expressed seen interest in utilizing off-the-shelf self-therapy for the treatment of severe autoimmune disorders.
Speaker 4: where there is a significant need for therapeutic solutions that can effectively reset patients' immune system and meaningfully improve patients' quality of life.
Speaker 4: In preclinical models, we are currently assessing the potential of FT819 to selectively target the
Speaker 4: as well as for the potential of F-Q522 as monotherapy and in combination with CD-20 and CD-38 to thresholded and mon Mädly
Speaker 4: to selectively target and durably deplete pathogenic B-cells, plasma cells, and autoreactive T-cells.
Speaker 4: We believe the value proposition for an off-the-shelf cell therapy in autoimmune disease is compelling.
Speaker 4: Unlike autologous CAR T cell therapies, off-the-shelf cell therapies avoid the need to taper a patient's immunosuppressive therapy.
Speaker 4: prior to the harvest of T cells from any fracture.
Speaker 4: Additionally, as many autoimmune diseases are marked by moderate to severe disease flares, which require timely intervention.
Speaker 4: The potential to treat on demand with an off-the-shelf cell therapy is a significant therapeutic advantage.
Speaker 4: We are currently working to extend our IPSC product platform into auto immunity in 2023.
Speaker 4: And we look forward to sharing our development plans and strategy as we generate additional preclinical data and further advance our first off-the-shelf product candidate toward clinical development.
Speaker 4: Before we close, I would like to sincerely thank our employees whose patience and perseverance have allowed us to emerge through this transition period with a strong foundation, a sharpened clinical focus, and multiple pathways for value creation over the next 12 months.
Speaker 4: I would now like to open up the call to any questions.
Speaker 2: Thank you. And as a reminder, to ask a question, simply press star 11 on your telephone and wait for your name to be announced. To withdraw the question, simply press star 11 again. Please stand by while we compile the Q&A roster.
Speaker 2: In our first question, come from Tyler Bamburin with Collin. Please go ahead. Hi guys, this is Tara on for Tyler today. So congrats on the progress so far. It's great to see you guys doing well these days. And...
Speaker 5: So, I guess my question is around the trial that could be starting in the second half. So, I was hoping you could tell us more about your agreed-upon study design and potentially what's left to do prior to initiation. And then, you know, regarding the study design, what cohorts do you plan to pursue?
Speaker 6: Yes, that one, yes.
Speaker 4: Sorry. Okay, thank you. Thank you. So, happy to go through this and I'll let Wayne walk through this. Keep in mind this is a draft clinical schema.
Speaker 4: And so we'll discuss it in proposed format.
Speaker 3: Yeah, so that's a good question. And you know, next is the study design scheme for FTP 5-2 reflects your past experience with other NK self therapies. And we're leveraging that experience.
Speaker 4: you know to propose a schema whereby we administer multiple doses of FT-522 in combination, you know with rituximab on a dosing schedule, you know, whereby you're following around a condition in chemotherapy, we give up to three doses of FT-522, you know on a fairly compressed schedule.
Speaker 4: And as Scott mentioned, we intend to look at the administration of 522 with and without conditioning chemotherapy. So our phase 1 dose escalation scheme reflects parallel assessments of both of those regimens in patients with relapsing fracture and inflammation.
Speaker 2: Okay, thank you so much. Look forward to seeing that. Thank you. For our next question, please.
Speaker 2: And it comes from the line of Jegal Nokumovitz with Citi. Please go ahead. Let me go over here a little bit.
Speaker 4: Hi, team. This is Ashraf Mubarak on Fregal. Thanks for taking my questions. Just building on the last one, it sounds like your plan for FT-522 is to combine with Rituximab in earlier line or maybe in front line BCLs.
Speaker 3: I guess, can you give us a little clarity on why you think you can sort of move straight into an early line setting with this combo? Maybe why are you getting away without having to go into later lines first and without having to show some monotherapy activity? That'd be very helpful. Thanks. Yeah, just to be clear, we are not starting with frontline patients. We do think that the potential regimen in the combination of 5, 2, 2...
Speaker 4: and re-protection have.
Speaker 4: can seamlessly plug into regimens that are used in the frontline, for instance, like Archop. And with 596 historically, we've explored the potential to combine with, for instance, standard care regimens like Archop in frontline or early line patients. However, we expect to start in patients.
that have at least have to rest on it, at least one line of therapy, and specifically, or a talks about regimen. Sorry, that's very helpful. I could ask one on FT576.
We've talked quite a bit about the sort of combinability with the anti-C38 antibody. So I'm just thinking a couple steps ahead towards maybe future.
or registration development, do you think it's necessary to have to show contribution of parts for the combo?
And how are you thinking about the contribution of their tumor lab, especially within the context of patients that may have already cycled through the CD38 antibody? Thanks.
I think I can talk about this from at least some experience with FDA interaction that we had with 596 and we're talking about it in the past.
So long as we think that we're down line of a regimen, for instance, where rituximab is used in the patient, for instance, in that setting previously had experience with CD20 monoclonal antibody therapy, we don't necessarily think you have to show contribution of the parts through a clinical study.
associated with retoxamab. Keep in mind that for instance in the lymphoma setting we are not giving retoxamab on a standard dose or dose schedule. We're not giving retoxamab that it needs to start in combination with a standard retoxamab regimen. So we are a bit of field from what we would consider sort of a standard retoxamab load appellars, you have al? recommend
at least in our initial clinical experience as well as potentially in some of the areas that we would look to develop registration studies. I do think there is so long as there is clinical data that is out in the field that you can benchmark to with respect to what monotherapy activity.
might look like with those monoclonal antibodies in specific lines of patients. Like I said, I don't think you would necessarily have to run a study where you saw, you would show discrete contribution of parts. I mean, quite frankly, the FDA even gave us feedback in the cell lymphoma that, you know, arguably, keep in mind that prior protocol, we combined with a single dose of rituximab.
We have to acknowledge that some level will be unethical to give the patients a little bit of support for toxin. Very helpful. Thanks very much. Thank you. One moment for our next question, please.
Any comments from the line of Kazin-Admoud with Bank of America please proceed.
Hi. Good afternoon, guys, and thank you for taking my question. Just maybe a couple points of clarification, if I could, Scott. For either FP576 or for 819, should we be expecting any updates at some of the appropriate medical conferences, for example, ASH this year?
And then 4, 5, 7, 6 again, do you have any sense of how many more dosing cohorts you'd want to complete before progressing into the Phase 2?
So for the clinical programs 576 and 819 not committing to provide a clinical update at ASH this year, I do think both programs are well positioned where we can provide a clinical update within the next 12 months, but not necessarily this year at ASH. So I wouldn't, I'm not prepared to commit to an update at ASH.
provide what we, at least our preclinical models, would suggest significant clinical activity. And I think that dose cohort, if you will, that we plan to enroll in the beginning of the middle of this year, second half of this year, will provide us a really good guide as to where we think we are with that program and the go-forward strategy.
where we, at least our preclinical models, would suggest significant clinical activity. And I think that dose cohort, if you will, that we plan to enroll beginning in the middle of this year, second half of this year, will provide us a really good guide as to where we think we are with that program and the go-forward strategy. Okay, thank you.
Oh great, thanks so much for taking the questions. Just on 522 in autoimmune disease, what, as you think about the clinical program, I'm curious around what you're thinking would be appropriate sort of translational markers to really understand the therapeutic window there. And then I just had a question on cash and just the difference between
quarter was obviously really heavy in contributing to the annual guidance, but I'll let Ed go through that in some detail. Go ahead and then I'll come back to you. Great, thank you so much.
Hi Mara. As I try to indicate in my prepared marks, there are a number of one-time items, particularly in the first quarter, that impact sort of cap in cash somewhat differently. So clearly the determination of the Janssen collaboration required us to record a lot of deferred revenue, both in the form of the upfront...
after this quarter and you'll see a more predictable run rate beginning in the second quarter and through the rest of this year. On a cash basis we have received almost all cash, or paid out all cash associated with termination. We received early in the second quarter the amounts associated with the wind down of the Janssen collaboration, so that was received in the second quarter.
And then, with respect to F-152, I mean, obviously there's been some really exciting clinical data with Autologist CD19 targeted therapy in certain auto-subioral auto-need diseases. We're certainly, you know, looked at that in KLO and the best data we've talked to, we certainly looked at that data with the entry. We have obviously been able to run certain pre-clinical models work, for instance, we have swarced peripheral blood.
from disease patients. And we've looked at, for instance, the activity of 819, 522, plus or minus monoclonal antibody, and compare that to autologous, you know, sorry, what in this case would be healthy CAR 2 cell therapy, donor-derived healthy CAR 2 cell therapy in those models with respect to clearance, for instance, durable clearance, for instance, of B cell populations. We also have some translational data from some of our studies and some of our studies from our research on the effects of COVID-19 on patients. So, thank you for your attention. Thank you. Thank you, Dr. Fauci. And I'm going to stop here. I'm going to stop here. I'm going to stop here. I'm going to stop here. I'm going to stop here. I'm going to stop here. I'm going to stop here.
with 596, where some of those patients actually did have, you know, functional B-cell compartments at outset, and we've seen durable depletion of that compartment. Thank you. One moment for our next question.
And it comes from Mike Ault with Morgan Stanley . Please proceed. Yep. Hey guys, thanks for taking the question. We just one on 522.
You mentioned, Scott, being able to start at a sort of clinically relevant dose. That's just your plan, but just curious if you could see FDA pushing back on that and maybe having to start at a lower dose than planned.
about ADR because we think it allows the cell to function in the background of a competitive and allo-competitive environment. But we also recognize that ADR is a potentiating signal and fundamentally does activate the cell to provide increased NK cell potency.
different than what we have had to go through with 596, but we are proposing starting with a three-dose schedule, and we are proposing starting at a dose level that is of 300 million cells per dose. And clearly with 516 and 596, we saw activity at 300 million cells per dose, including single dose.
So we think three times 300 is a reasonable place to start from a proposal perspective with the FDA.
from the line of Peter Lawson with Barclays. Please proceed.
Hi, this is Shay Feeney on for Peter Lawson. Thanks for taking our question. And maybe just to start a quick clarification around 819 and 576. you mentioned maybe data in the next 12 months, but not likely ash. Should we be thinking this might be an investor update around year end 2023 or more likely you'd want to save it for a medical meeting.
in 2024? And then secondly, how should we be thinking about balancing development efforts for CAR-T versus CAR-NK and if there's any...
how that might evolve over the coming a year or so, whether there may be more increasing interest in CAR T. Thank you. Sure. Now, I'm not prepared today to commit to when our clinical updates will be around 8-19 or 5-7-6. I mean, obviously we'll continue to enroll patients and as we generate what I consider to be a new
meaningful and complete data sets that guide our path forward in a more definitive way, having shared the data at that time. I think we will be able to provide that guidance within the next 12 months, whatever we are able to do that by the end of this year to be the, I think, its own work with, but certainly within the next 12 months. With respect to the balance of NK cells and T cells a much.
I don't think we necessarily think of our portfolio that way, whether in competing NK versus T. I think we evaluate each of our programs on an individual basis and that the value that they can bring to patients and create for the company. We absolutely are strong believers in NK cells. We think NK cells provide.
wonderful activity in combination and synergized with monoclonal antibody therapy. They've obviously proven very safe and effective where the combinability seems to be unmatched and we do think an MK cell can reach into compute community-based settings in combination with standard care immuno- chemotherapy regimens.
With prospective T cells, you know, our first T cell program is a solid tumor, is obviously a hematologic malignancy and solid tumor. We've done a lot of work with NK cells and T cells in solid tumors. I think as we continue to build out our solid tumor pipeline, we will likely continue to develop and advance.
T-cell programs in solitude? Share this, I'll answer your question.
Yes, thank you so much. Thank you. Thank you. Thank you.
Any comments from the line of Michael Yee with Jefferies, please proceed.
with respect to their ability to functionally persist, increase activity in the background of our next models. I'm involved in even talk to it, but I'm happy to send you the post. There's an entire presentation at Ash on the EDI technology.
Maybe you can follow up after the post picture.
And does that mean you could potentially read those patients if you don't give them chemo? Yeah, we already read those patients with NK cells. Thank you. Thank you. One moment for our next question, please. And it comes from the line of Dinah Gray-Bosk with SBB. Your securities, please proceed. Great. Thank you for the question. I wonder if you could speak to the path, both steps and timing to bring FT-522.
as we generate more preclinical data both with 819 and 522. I will say, I do think, for instance, 819 as an example, we have clinical experience. We have safety data with 819, and it does have, to date, a pretty favorable safety profile. So I think one of the pathways forward, as you can imagine with 819, is given there's clinical data, there's a safety package, there's a history there. I do think it could be a fairly straight line with respect to expanding the 819 into autoimmunity. With respect to 522, to be fair, we don't have clinical experience yet. And so it may, a pathway into autoimmunity with 522,
may require some, and we may require for our own benefit, some initial safety data before we would be willing to pull the trigger on advancing 522 into patients. We do think we can generate that initial safety data as we start, as we mentioned, begin dosing patients with 522 in the second half of this year.
Thank you. One moment for our next question.
And it comes from the line of Andrea 10 with Goldman Sachs. Please proceed.
Hi, everyone. Thank you for taking my question. Scott or maybe Wayne, just curious if you're thinking on the approach with FT576 has changed at all given the strength of the Cartitude 4 data. And then can you also remind us how your novel binder differs from that in the CARV-VIC-D construct? And maybe just based on the early data from ASH, how de-risked do you think that is? Sure, I guess.
I think the obviously the data that we've seen with Janssen Apollo-Vescartes cell product has been quite remarkable. I'm sure we will all be wowed at EHOP with the data set. I think at the end of the day the reality is in my lawn where there will be continued to be multiple lines of therapy that patients will experience.
throughout their care. I think that will continue to mark myeloma. It's fragmented, it's complex. Most patients are treated in community-based settings as part of monoclonal antibody-based regimens in many cases. And I don't really expect that to change.
I don't think the vast majority of patients will be cured with autologous car teeth cell therapy. There will continue to be lots of patients treated, pre and post autologous car teeth cell therapy. With respect to your outbinding domain, maybe I'll turn it over to Bob and you can talk a little bit about our binding domain.
Sure. Similar to the veterans binder, our binder for BCMA has a very good specific activity in terms of high affinity in targeting the antigen BCMA. In the 2018 molecular therapy paper, it was shown that we can target cells that have the order of 100 antigen per cell as opposed to most.
Great, thanks so much.
Great, thanks so much. Thank you. One moment for our next question.
This is Carolina Ivanez-Dentoso for Ben Burnett. Thank you for taking our question. I was wondering as well if you could provide more color on your comment that combination regiment along the functional persistence of FD576 and if you also could quantify the obsess extension there.
Sure, I mean, I'll actually let Bob talk to that.
It obviously comes from translational data in the study, but I'll let Bob speak to that with respect to the impact that DARA has with respect to their patient's immunoconstitution profile and how that potentially creates a favorable environment for extension of persistence. Sounds like Scott already answered it, but...
But by adding the additional factor of daratumumab, you're able to suppress the reconstitution of CD38 positive cells. So this is majority of the NK cells and a subset of the T cells, and the activated, most likely the alveolar active T cells. So inherently, the favorable condition that Scott is talking about is associated with maintaining space and cytokine availability during that 30-day period.
above and beyond what sites will on its own brink. So now you have a cell therapy that's in a more favorable space or environment which leads to enhanced persistence. Okay, very interesting. Probably I've missed this, but have you called out any of the immune diseases that you think will be suitable for your cell therapies?
We've not done that yet, no. Okay. Thank you. Much appreciated. Sorry. We've not done that publicly. Right. Yeah. Okay. Thank you. Understood. Thank you very much.
We've not done that yet. Okay. Thank you. We've not done that publicly. Right. Yeah. Okay. Thank you. I'm the food. Thank you. One moment for our next question.
It comes from the line of Yanan Xu with Wells Fargo. Please proceed.
Thanks for taking our questions. A few questions on FG522. The IND has been submitted. I'm just wondering, have you been accepted? And if not, yet, do you anticipate any potential?
questions from the agency. And the other question is on the study design, because there seems like there are a few moving parts with or without nofas depletion. And I'm not sure whether, you know, with or without CD20 is also a perimeter.
With all that said, would this have more like a sequential design with lympho-depletion first and then evaluate no lympho-depletion, or would it be more like a parallel design? I have a couple of follow-ups on this program as well.
Thanks. Okay. So, again, I'll speak in terms of it's a proposed clinical schema. The proposed clinical schema starts at multi-dose, and then it's at multi-dose.
and at multidose at 300 million cells per dose. That's the proposed clinical schema.
The initial patient cohort would be with Cy-Flu. The clearance of that cohort, that initial patient cohort, would allow for two things. Number one, continued dose escalation with Cy-Flu, as well as number two, the
the opening of a second arm where that second arm would not have side flu conditioning and that second arm could then independently operate and dose escalate. That's the proposed scheme.
Very helpful. And then I'm wondering, a key question or a question of interest is how could this inform whether the ADR worked as intended? Could you... I grew up in dirt so a lot of it's funny. You were a big distrust you didn't die one day. roadway. OK.
share some potential biomarkers that you might be looking at to vet that. And also when might we see the data on that? I'm assuming it's probably before we have the data for the clinical efficacy.
So yeah, I saw that. Thank you. So certainly not going to commit to data discorders on F-T-5-2-2, given the stage of where we are with that program at this point in time. I think Bob can talk about sort of...
biomarkers associated with that, but obviously we are comparing in this study in some respects head-to-head plus or minus 522 plus rituximab plus or minus side flu. So I think there's a whole host of translational data that we will be able that will help us elucidate the impact of the ADR construct.
I don't know if you want to make any specific comments. Some of the obvious biomarkers will be up in PK. With site flu and without site flu, this is a very interesting study. I'm very excited about the data that will be coming in.
For example, with Cy-flu, you will get the constitution around the second week. This will have ADR in place. So we will be looking for a boost in activity over the course of the 30-day treatment cycle, something that wouldn't be possible without ADR as it constitutes.
on the other side, without cycling, first of all, we're looking for response, of course. But we'll also be looking for persistence in a very saturated system filled with patients and needs. So a lot of exciting things to look for, a lot of markers associated with 4-MVB, expressions to be 38, expressions to be 20, expression, and just tracking the cells.
basically persistence over the multiple dosing application over the course of the first two weeks and thereafter. Only thing I would add is that, you know, from a clinical endpoint perspective, clearly the most definitive evidence that the ADR is working is demonstration of an objective response in patients who are treated with FT-532 plus rituximab without conditioning chemotherapy.
I think we're all aware that sometimes data interpretation may be difficult because fluid therapy and cyclophosphate impart some degree of antitumor activity. If you are able to see objective responses without that, that's pretty clear evidence that the ADR is working at these in terms of facilitating antitumor activity with EFT-522.
Got it. Very helpful. If I may have a quick final question. I'm just a little curious. By using 4-MBB as a CAR target, you probably also limit the 4-MBB expression on the NK cells.
themselves on the current T cells themselves. Would that impair NK function in any way?
cells, on the current T cells themselves. Would that impair NK function in any way? Yeah, it's a good question. We looked at it.
Obviously, we're not confident. There is no impairment.
We're confident there is no impairment, but we're not going to discuss it beyond that.
Thank you for taking all the questions. Thank you. One moment for our next question. This question comes from Matthew from Oppenheimer. Please proceed.
Great, thanks guys. So this is Matt Hagen on format. Thanks for squeezing us in. Just curious if you could speak to or expand on maybe why you think...
The ADR technology could be a superior approach versus some of the other approaches out there for me and cloaking like HLA knockouts, for example, things like that. Thanks. I'll turn that over to Bob, and I'll start by asking Bob to limit his response to it most two minutes because he's going on for an hour.
It might be strong, it's very biased, so take everything from that perspective. You know, as we've talked about it in previous calls, we obviously appreciate how other folks are trying to move forward with their stealth technologies, but all the other technologies in our opinion are interior because...
While they avoid one situation, they embark on another situation. For example, class 1 deletion results in obviously missing cells and a target on the back of the cells for NK cell recognition and elimination. We also have seen that missing cells also impede effector function. So a lot of negative things come when we knock out HLA class 1. But when you do so, you also have to think about missing cells. As I mentioned, you expressed things such as HLA-E.
That's not a very broad approach because a lot of the NK cells have NKG2C, which is an activating receptor upon engagement with HLAE. So you're actually provoking a stronger attack. Things like CD47 in our hands do not overcome the challenge of looking self because self alpha is not expressed on NK cells.
So for us ADR is the most comprehensive approach to replace 5-flu. There are other strategies that come up short in trying to get rid of all the parameters that 5-flu brings to the table. ADR in our opinion is the only one that can truly replace 5-flu.
I think the other thing that I would add is obviously a lot of these knockout strategies, if you will, or overexpression strategies are, I would call them sort of single mechanistic with respect to intent. They're intended to hide the self, which again, may add value. I'm not suggesting that. They're the ones that have the ability of Despite the places of intent, right?
But the ADR technology, importantly, is intended to also activate the cell. It is a potentiation signal, as you mentioned. It is a core construct. And we do think, in the field of allogeneic cell therapy, continuing to be able to potentiate these cells.
It is an important ingredient to being able to boost efficacy. Got it. Very cool. Thanks, guys. Sure. Thank you. One moment for our next question. It comes from the line of Jack Allen with Baird. Please go ahead. Okay.
conditions that you would be considering for development beyond BCL. We're aware of a CD19 CAR-T investigator-led study for treating lupus and wondering if you had any thoughts on other studies that could provide proof of concept for a similar approach using NK cells. Thanks. We appreciate it.
Yeah, we do. We have quite a bit of feedback from KOLs and some investigators with respect to multiple different severe autoimmune diseases. We are not going to comment on this call at this time.
As I mentioned in our prepared remarks, we're happy to provide at the appropriate time as we solidify our plans and advance towards clinical development or specificity.
Great. Thank you all for your participation in today's call. Appreciate all the good questions. Look forward to speaking to all of you soon. Be well.
And thank you. And this concludes today's conference call. Thank you for participating and you may now disconnect.