Earnings Transcript for FATE - Q3 Fiscal Year 2023

Operator: Welcome to the Fate Therapeutics Third Quarter 2023 Financial Results Conference Call. At this time, all participants are mode. The call is being webcast live on the Investors section of Fate's website at fatetherapeutics.com. As a reminder, today's call is being recorded. I would now like to introduce Scott Wolchko, Present and CEO of Fate Therapeutics.

Scott Wolchko: Thank you. Good afternoon and thanks everyone for joining us for the Fate Therapeutics third quarter 2023 financial results call. Shortly after 4

Ed Dulac: Thank you, Scott, and good afternoon. Fate Therapeutics is in a solid financial position to advance our pipeline, our cash, cash equivalents and investments at the end of the third quarter for approximately $350 million. In the third quarter of this year, our revenue declined to $1.9 million compared to $15 million for the same period last year. As indicated last quarter, our revenue is now derived exclusively from our collaboration with ONO Pharmaceutical, and specifically reflects research funding associated with the development of a second product candidate against an undisclosed target in solid tumors. As a reminder, after opting into a U.S. and European co-development and co-commercialization arrangement with ONO for FT825 in the fourth quarter of last year, we now account for that program's reimbursable expenses as an offset within our research and development costs. We recognized $2.1 million of contra R&D expense in the quarter. Research and development expenses for the quarter decreased by 57% to $34.3 million. The decrease in our R&D expenses was attributable primarily to a decrease in salaries and benefits, including share-based compensation expense following the company's restructuring in the first quarter, and from lower clinical trial costs and lower demand for R&D materials and equipment. General and administrative expenses for the third quarter decreased by 12% to $18.9 million. The decline in our G&A expenses was attributable primarily to a decrease in salaries and benefits, including share-based compensation expense. Total operating expenses for the third quarter declined 47% to $53.2 million, which includes $10.1 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 assess the fair value of these contingent milestone payments currently valued at $700,000 on a quarterly basis. In the third quarter, we recorded a non-cash $1 million non-operating benefit associated with the change in fair value. Our net loss for the quarter was $45.2 million or $0.46 per share. Finally, we reiterate guidance for full year GAAP operating expenses to be in a range of $265 million to $285 million, and that our year-end cash and investments will exceed $300 million. I would now like to open the call for questions.

Operator: Thank you. [Operator Instructions]. Our first question comes from Yigal Nochomovitz with Citi. Your line is open.

Ashiq Mubarack: Hi, guys. This is Ashiq Mubarack on for your Yigal. Thanks for taking the questions. I just have a couple. For FT522 in the Phase 1, I am just curious if you think if there is a certain threshold in drop off and engraftment or maybe activity that you believe would be acceptable between patients who receive preconditioning versus those that don't? Or does there really need to be no drop-off for you to utilize that preconditioning free regimen in future studies? Thanks.

Scott Wolchko: Yes, I don't I think when we look at the data, I think the data is really going to be driven by the end of the day, patient outcomes and responses, we are definitely interested in understanding the PK profile of FT522 with and without conditioning. And I think that would be help of guide dose escalation. But ultimately, I think it's about patient benefit and driving patient benefit, potentially with no conditioning, as that being the important element of 522 with respect to its unique profile.

Ashiq Mubarack: Okay. Understood. We will just have to see. I guess for, FT825, I know you have the cetuximab combo. But are you also planning to combine with trastuzumab or maybe trastuzumab direct you can, given different given the differences in binding dynamics you showed SITC. I am just curious if you think an ADC combo might be something that's actually viable from a safety standpoint, given your comments around the HER2 low opportunity? Thanks.

Scott Wolchko: Yes. Absolutely. We have started this study with combination with cetuximab, but we certainly think there's opportunity to broaden the clinical profile to include other monoclonal antibodies. There are several that we're looking at. One of those possibly is actually trastuzumab since there does not appear at least preclinically to be competition between the binding domains. And in fact, we've actually seen, and I believe we've presented this publicly, we've seen quite nice synergy in fact with FT25 and trastuzumab.

Operator: Our next question comes from Michael Yee with Jefferies.

Unidentified Analyst: This is Jenna from Mike. Thanks for taking our questions. We wanted to get your latest take on the landscape. The CD-19 CAR-T is moving into earlier lines and there are new players coming to the market CAR-T and going after post CD-19. So in the context of all of that, where do you see the next-gen CAR NK program, CD-19, ultimately fit into that landscape? And secondly, are you able to comment on how you're doing on enrollment? Have you enrolled any patients and how soon you think you may be able to start the no chemo arm?

Scott Wolchko: Sure. Not going to comment on enrollment other than to reiterate the comments we made on the call where the study open for enrollment was not announced. The first patient the first no conditioning patient, if you will, that patient has, could be as enrolled as early as patient four. We are required to clear the first dose level in the conditioning arm before opening the no conditioning arm. So first assuming no DLT, the first three patients would receive conditioning and then two events can occur simultaneously. Number one, you can dose escalate the conditioning arm as well as open the no conditioning arm. And so the fourth patient could be a no conditioning patient. In terms of the landscape, completely agree. It's a super competitive landscape and I think they're -- I think at the same time there are multiple opportunities that can exist from an off-the-shelf cell therapy. I've talked extensively in the past that I absolutely believe there will be a line of therapy that is of allogeneic or off-the-shelf that can exist and will exist post auto car t-cell therapy. I think there's significant need that exists, whether it lymphoma or myeloma in post auto car t-cell patients. In addition, I think one of the exciting elements of cell therapy, again, to be explored, determined is the potential, especially within NK cell, is to plug into standard immunotherapy regimens, for instance, like in R-CHOP or an earlier line regimen in myeloma. I think those opportunities exist. I think one of the challenges that exists with whether it be autologous or allogeneic cell therapy. And today, those regimens bring s flu along for the ride. So if you want to combine with an existing regimen and reach patients early, including in the community setting, one of the hurdles to overcome potentially is cy/flu. And that's one of the reasons we're very excited about 522 and ADR. And the potential to reduce, significantly reduce the dependency on conditioning and enable a more seamless combination with off, with standard regimens that are used earlier in care in the community.

Operator: Our next question comes from Tyler Van Buren with TD Cowen.

Tyler Van Buren: As we think about the next 6 to 12 months, what will the one or two major value creating events be in your view? And what should investors expect from them?

Scott Wolchko: Yes. I think, high -- the three that I think are worth just noting were on I highlighted with my comments. I think we have an opportunity to develop, to demonstrate proof-of-concept with FT522, including in a cy/flu regimen. I think that's, it can be a pretty game change -- there can be game changing cadet potential if you can deliver cell therapies without conditioning chemotherapy. And essentially for all intents and purposes, make a cell therapy look like a monoclonal antibody therapy in terms of how it can be delivered and reach patients. I think that's pretty game changing if we can demonstrate that with 522, it's ADR built in and no cy/flu. Also, very excited about FT825 as you are probably well aware, there's been a lot of challenges in the solid tumor setting with CAR T cells historically. I think there certainly have been toxicities of note, and I think the activity has been modest at least compared to hematological malignancies. 825 being a pointed edited cell therapy, and what I'll just sort of consider to be a fine-tuned binding domain against HER 2, I think early on in that study, given that we're starting at a 100 million cells, we do have the opportunity potentially to show responses and I think -- and safely show responses, and I think that would be a significant breakthrough with respect to the use off-the-shelf cell therapies in solid tumors. And then finally, I'll note, and I did note it in our call, moving into autoimmunity. I think, we are one of the first companies to pioneer an off-the-shelf strategy in autoimmunity. I realize we're all sort of beginning this journey at the same time, both autologous and allogeneic. And I think the potential to show, for instance, what's been shown with the autologous programs in a small number of patients that you can durably deplete an aberrant b-cell population, enable reconstitution of a healthy immune system and do that in a durable way, I think could be really powerful.

Operator: Thank you. Our next question comes from Daina Graybosch with Leerink Partners.

Daina Graybosch: I wonder if you could talk about for autoimmunity, why start with FT819 rather than going to FT522, and how you think about both of those products and their potential ultimately in autoimmunity.

Scott Wolchko: Yes, I think FT819 obviously, and we've sort of alluded to this, has human clinical experience. To date has a highly differentiated what we consider to be safety profile. It's readily available off-the-shelf and there's certainly strong proof-of-concept for autologous CAR t-cell therapy. And as we have shown anti-tumor activity, including complete responses with 819. So I think there is a very strong rationale for off-the-shelf cell therapy in autoimmunity, and at least in the cancer setting, we've seen all the sort of safety and activity hallmarks that we believe can have a differentiated profile in autoimmunity. We've talked about 522 and potentially the benefits of an NK-cell, which again, has an exquisite safety profile in oncology. I think with FT522, there is potentially a broader therapeutic appeal, including and especially if the ADR technology allows for reduction or elimination of conditioning chemotherapy, which I think is somewhat of a barrier, obviously, in autoimmunity is certainly more so than in oncology. And with FT522, as you know, we have the potential to combine with monoclonal antibody therapy. And I think with FT522, we are looking at, call it, sort of a broader array of potential autoimmune diseases that we could target giving the multiple mechanisms of action that will going to in FT522 beyond CD19 targeting. So whether that be, for instance, targeting CD20 with a monoclonal antibody, CD38 with a monoclonal antibody, or potentially be targeting auto reactive, 4-1BB expressing T-cells. So I think the FT522 profile has -- FT522 product candidate has potentially much broader reach than a CD19 targeted cell therapy.

Operator: Our next question comes from Mike Schmidt with Guggenheim.

Kelsey Goodwin : This is Kelsey on for Michael. Thanks for taking our question. I guess specifically for 825 in in HER2 solid tumors. I guess, what types of tumor should we expect in the Phase 1? And I guess, what kind of efficacy benchmark are you thinking about, as we kind of get those patients in? Thank you.

Scott Wolchko: I think the efficacy is going to be judged by the particular patients that were looked that, that we will ultimately enroll. There is a fairly broad enrollment or inclusion criteria in the study. It is not limited to, for instance, or to IHC 3. So we can certainly, enroll patients that are both high and low expressers of HER2 into that study.

Operator: Our next question comes from Peter Lawson with Barclays. Your line is open.

Peter Lawson: Great. Thanks for the update. Thanks for taking my questions. Just on the solid tumor program, so circling back on that. The learnings from your prior NK cells sales in solid tumor that kind of rolled over to the current program. So what were the learnings there? And then it is redirected T-cell. Where do you think that would fit in the treatment paradigm?

Scott Wolchko: Yes. I think, while we have shared some of the data that we have seen in NK cells with solid tumors, in the setting of solid tumors, including CAR NK cells, where with our most recent version of, in solid tumors with FT536, which was the CAR NK product candidate. We certainly saw activity, at a 100 million cells per dose. So I do think there is interesting activity that we have demonstrated in the past with off-the-shelf cell therapies. Think it would be premature for me to say, comment on, what do you know with respect to an NK cell versus T-cell. I think they are just very different sort of cellular vehicles, if you will. So I don't necessarily think you can extrapolate what we have seen in a small number of patients with NK cells to the sort of the T-cell vehicle, if you will. So, we don't really do that sort of cross comparison between NK cells versus T-cell, especially in a solid tumor setting. And knowing quite honestly, all the incremental innovation that's building A25.

Peter Lawson: And then I guess the follow-up question was just on, where you think this her two directed T-cell would be positioned in…

Scott Wolchko: Yes, I think it's too early to comment on that. I think, as we look at the HER-2 landscape obviously, what's being demonstrated with the ADCCs are pretty remarkable. But I think what we're excited about at the same time is that, again, solid tumor settings, patients are relapsing for significant unmet need. And I think what we're excited about as well is, there seems to be activity in HER-2 expressing tumors that cover a breadth of different types of solid tumors. So I think that we're now seeing HER-2 starting to become validated, especially if you're able to target her two low not in what you would think of just the traditional setting, for instance, of breast cancer. So, I think, the opportunity for safely targeting HER-2 in the solid tumor space is significantly expanding.

Operator: Our next question comes from Andrea Tan with Goldman Sachs.

Unidentified Analyst: This is Tani on for Andrea. Thank you for taking our questions. Firstly for FT819, would you mind just sharing a bit more about the rationale for choosing lupus as the initial autoimmune indication? And then secondly, if you could provide a bit more details around the clinical trial design for the Phase 1 study.

Scott Wolchko: Yes, I think, the rationale for starting lupus is there's strong clinical precedent for CD-19 targeted therapy, and there's significant enthusiasm from the lupus community in treating patients with cell therapy. So I think it's a terrific place to start. The trial design, I alluded to on the call, it's a pretty standard design with respect to a cell therapy that we're seeing that others are exploring. It is a dose escalation study. We can treat at multiple escalating doses, stepping up at three times the previously cleared dose level, each dose level, each and every dose level that clears DLT is able to expand and enroll 10 patients in expansion. So you can explore multiple different dose levels and multiple different expansions assuming that, that dose level has clear DLT. We are able to enroll patients with lupus nephritis as well as patients with other organ involvement.

Operator: Our next question comes from Yanan Zhu with Wells Fargo.

Yanan Zhu: First on the lupus study for FT819, I was wondering -- I think you mentioned that lympho depletion regimen is standard. I'm wondering, how does it compare with the German group's lympho depletion regimen and also if…

Scott Wolchko: It's exactly the same regimen.

Yanan Zhu: And another question on FT522, and for the non-lympho depletion regimen, I was wondering 300 million times three, that dose regimen at the starting dose, what's your expectation in terms of how much T cells can that dose remove? Do you think it's -- it could be possible that that's enough to remove all the T-cells or you might need to dose escalate simply on the basis of clearing more T cells as opposed to optimizing for anti-tumor activity?

Scott Wolchko: Difficult for me to answer that question today. We're certainly going to prioritize translational data in understanding differences between the doses. Keep in mind that, this is not all about, at the end of the day, it's not really about lympho conditioning through ADR, it's about the ADR technology, potentiating the NK cell. And so, the mechanism of action is not necessarily here to condition and remove all T-cell. Not all T-cells express 4-1BB in fact only, for instance, the alloreactive T-cell compartment is the primary expressor of 4-1BB. So this is not really a lympho conditioning approach. It's meant to defend the cell from potential forces of rejection. It's also a receptor. It is a CAR against 4-1BB, so it potentiates the NK cell and provides additional activating signal. And at least in preclinical models, we've seen synergistic activity between NK cells and T-cells and increased anti-tumor activity.

Yanan Zhu: Got it. That's very helpful. And then lastly, in terms of your consideration for FT522 for autoimmune disorders, I was wondering what might be the catalyst that prompt that decision? Would it be the observation in this cancer study, and see how the non-lympho depletion regimen is doing? Or is it something else? Thank you.

Scott Wolchko: Yes, I think the 522 study in oncology certainly can inform how we design the study in autoimmunity or study in autoimmunity with 522. I think, quite honestly, at least as I sit here today, I could imagine a study with 522 in autoimmunity that actually would test something very similar to what we're doing in oncology plus or minus cy/flu.

Operator: Our next question comes from Etzer Darout with BMO Capital Markets.

Etzer Darout: Just a question here on the systemic lupus program. Are you -- the preclinical data that I'm assuming you've generated, when could we see the data there if you are indeed generating that type of data, and then ultimately just getting us trying to get a sense of how you think that the platform here with 819 compares to sort of some of the emerging data around other assets that are exploring sort of systemic lupus. Thank you.

Scott Wolchko: Sure. I mean, there is a slide in our presentation deck or investor deck. It's in vitro, but it does look at, and I'll let Bob talk to it a little bit. It does certainly look at, for instance, the b-cell depletion with both 522, and 819 compares them head-to-head against, for instance, a primary T-cell, if I'm not mistaken.

Bob Valamehr: So our initial study doesn't apply to that. It's taken samples from healthy patients or healthy donors, SLE patients and lymphoarthritis patients, and we can clearly see a very distinct and specific elimination of the B-cell compartment within those three populations. But I would also reference you back to Michel Sadelain, the collaboration publication that we have had about a year ago now in Nature Biomedical Engineering where there is a whole slew of in vitro and in vivo studies showing the durability of the activity of FT819 in targeting B-cell.

Scott Wolchko: And then the final thing that we talked -- the other thing that we talked to in the past, which we have not presented yet publicly, but are looking for an opportunity to do that. In terms of clinical proof-of-concept, we have looked at cohorts of patients in both the 819 oncology study as well as the prior 596 study in oncology, wherein some of those patients, we were able to detect T-cells cells in those patients at baseline. And we were able to go back and look at, for instance, the kinetics and depth of B-cell depletion in oncology receiving a 819 and/or receiving FT596.

Operator: Thank you. And our last question comes from Mara Goldstein with Mizuho. Your line is open.

Mara Goldstein: Great. Thanks. So I just wanted to go back to the autoimmune question and really maybe to understand not so much FT819 versus 522, but 819 versus the rest of the field of cars. And then the other question is, do you think of 819 as a bridge into looking at other constructs in autoimmune in the same way, you went through that us with NKs.

Scott Wolchko: I think it's a little too early to know. I mean, the field is very enthused by the potential of taking cell therapies into autoimmunity. And in a small number of patients, and I would potentially say in a carefully selected number of patients, into academic studies, we have seen some pretty remarkable results. I think it is really early for the field. And ultimately, what are the therapeutic requirements that best serve patients and induce long-term drug free remissions, which I think is the excitement in particular about cell therapies. I think we are all going to learn a lot about that, quite honestly, in the next three, six, 12, 18 months as we explore -- it is the first versions of autologous and allogeneic CD19 targeted CAR T-cell therapies.

Mara Goldstein: And just on the on the autoimmune study, how many sites are you going to start in the U.S?

Scott Wolchko: Yes. We are working through that. I can think one of the strategies, quite honestly, with respect that we have heard, in speaking with folks in the field is that, in these early days, they really do like to partner as much as they can with an oncologist that has significant experience in CAR T-cell therapy. And so for us, as you know, we are running the 819 study in oncology and I think, somewhere between 12 to 15 sites are open. And so as we think about, how to most effectively get 819 off the ground in autoimmunity, we are excited to partner with some of those sites as an example, who are very familiar with 819 are currently enrolling patients, and provide that sort of partnering opportunity with the oncologist and the rheumatologist to treat patients.

Operator: That concludes the question and answer session. I'd like to turn the call back over to Scott Wolchko for closing remarks.

Scott Wolchko: Thank you. And thank you all for participation in today's call. Hope all of you make it out here for ASH in San Diego and happy to sit down and spend some time with you. Thank you very much.

Operator: Thank you. This concludes the program. Thank you for your participation. You may now disconnect. Everyone, have a great day.