Fate Therapeutics Q3 2023 Earnings Call Transcript

Quartr
Provided by Quartr
November 8, 2023

There are 8 speakers on the call.

Operator

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

Speaker 1

Thank you. Good afternoon, and thanks, everyone, for joining us for the Fate Therapeutics' Q3 2023 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 Web In addition, our Form 10 Q for the quarter ended September 30, 2023, This filed shortly thereafter and can be found on the Investors section of our website under Financial Information.

Speaker 1

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 statements on the company's earnings press release issued after the close of market today as well as the risk factors included in our Form 10 Q for the quarter ended September 30, 2023, 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, Fate Therapeutics disclaims any obligation to update these forward looking statements to reflect future information, events or circumstances.

Speaker 1

Joining me on today's call are Ed Dulach, our Chief Financial Officer and Doctor. Bob Valimer, our Chief Research and Development Officer. During today's discussion, we will cover several key milestones That we recently achieved for our iPSC product platform, including expanding the clinical reach of our iPSC derived CAR T cell platform to solid tumors as well as beyond oncology and A2 autoimmunity. In reaching these milestones, we are now well positioned to achieve important clinical readouts in oncology and autoimmunity across multiple programs in 2024. We will also discuss our continued focus on controlling costs That has resulted in a significant decrease in cash utilization, which we believe enables us to extend our operating runway into the second half of twenty twenty five.

Speaker 1

Beginning with FT-five twenty two, our off the shelf CD19 targeted CAR NK cell program. I am pleased to announce that our Phase 1 study is open for enrollment In patients with relapsedrefractory B cell lymphoma, where we intend to assess FT-five twenty two with and without conditioning chemotherapy. FT-five twenty two is the company's 1st product candidate To incorporate our proprietary alloimmune defense receptor or ADR technology, Which is comprised of a synthetic engineered receptor designed to target 4 1BB expressed on allo reactive immune cells and induce NK cell proliferation. In preclinical studies, we have shown that the engagement of ADR armed CAR NK cells With alloreactive immune cells, mitigated rejection, promoted NK cell proliferation and increased antitumor activity. These preclinical data suggest that 5/22 Has the potential to drive clinical responses without administration of intense conditioning chemotherapy to patients.

Speaker 1

The Phase 1 study includes 2 regimens. Regimen A or the conditioning arm, which consists of 3 days of standard conditioning chemotherapy, one dose of rituximab and 3 doses of FT-five twenty two. And regimen B or the no conditioning arm, which consists of one dose of rituximab and 3 doses of FT-five twenty two without conditioning chemotherapy. Enrollment into regimen A or the conditioning arm has now been opened at the first dose level of 300,000,000 cells per dose and upon clearance of dose limiting toxicities at this first dose level, Enrollment into regimen B or the no conditioning arm will commence at its first dose level of 300,000,000 cells per dose. Each regimen may proceed with dose escalation independently.

Speaker 1

Today, Conditioning patients with intense chemotherapy is a necessary component of the treatment course for cell based cancer immunotherapy, including for both autologous and allogeneic cell therapies. Conditioning chemotherapy induces toxicities, limits patient access and prevents combination with standard of care immunotherapies widely used in the community based setting. We believe we have the opportunity to establish clinical proof of concept for our ADR technology and for FT-five twenty two Program without conditioning chemotherapy early in dose escalation. Turning now to our T cell programs. We believe our multiplex engineered iPSC derived CAR T cell product platform is uniquely suited to bring a Constellation of antitumor mechanisms to the fight against solid tumors.

Speaker 1

I'm pleased to announce that we have established a new landmark In the field of cell based cancer immunotherapy, our IND application was cleared by the FDA to initiate clinical investigation of FT-eight twenty five in patients with solid tumors. The multiplex engineered iPSC derived CAR T cell program, which is being co developed Under our collaboration with Ono Pharmaceutical incorporates 7 novel synthetic controls of cell function that are designed to harness the potential of both innate and adaptive immunity and to overcome the unique challenges in treating solid tumors. These novel synthetic controls include a CXCR2 receptor to promote cell trafficking, a chimeric TGF beta receptor to redirect immunosuppressive signals in the tumor microenvironment and a high affinity non cleavable CD16 receptor to promote antibody dependent cellular cytotoxicity. At the 2023 Society For Immunotherapy of Cancer Annual Meeting, We unveiled that FT-eight twenty five incorporates a novel cancer specific antigen binding domain targeting HER2, Which was contributed by Ono to our collaboration. Preclinical studies presented at the meeting demonstrated that the binding profile of the Cancer specific CAR construct is unique and differentiated from that of Trustee's exhibiting similar potency with greater specificity toward HER2 expressing malignant cells.

Speaker 1

In subcutaneous xenograft models, FTA-two fifty five demonstrated robust antitumor efficacy against HER2 high as well as HER2 low expressing tumor cells. Additionally, FT825 resisted TGF beta mediated maintaining robust cytolytic activity across multiple rounds of tumor challenge and suppressive levels of TGF data exposure and showed potent migration to CXCR2 ligands, which are often expressed in solid tumors. With the clearance of our IND by the FDA, Phase 1 study start up activities are now ongoing at multiple sites. The dose escalation schema for the Phase 1 study includes 2 treatment regimens. Regimen A or the monotherapy arm Consists of a standard 3 day preconditioning regimen and a single dose of FTA-two fifty five as monotherapy.

Speaker 1

Enrollment is the monotherapy arm will commence at the first dose level of 100,000,000 cells. Eligibility includes patients with advanced HER2 expressing solid tumors. Regimen B or the combination arm Consists of a standard 3 day preconditioning regimen and a single dose of FT825 in combination with cetuximab, Where we seek to additionally exploit innate immunity by leveraging the product candidates high affinity non cleavable CD16 receptor to target eGFR expressed on solid tumor cells. Enrollment into regimen B will commence at the 1st dose level of 100,000,000 cells upon clearance of dose limiting toxicities at the first dose level of regimen Eligibility includes patients with advanced eGFR expressing solid tumors. While we have made great strides in advancing our most innovative and differentiated clinical programs in oncology, We also remain committed to pursuing new therapeutic opportunities beyond oncology, where cell based immunotherapies can have a Profound clinical benefit for patients.

Speaker 1

Our initial clinical data are now emerging, Indicating that CD19 targeted CAR T cell therapy has the potential to durably deplete a patient's pathogenic immune cells, Drive immune reset and meaningfully improve quality of life across a wide spectrum of autoimmune diseases. We believe there is a very strong value proposition for off the shelf cell therapy in autoimmunity, where a relatively short lived cell Can deeply eradicate an aberrant B cell population and enable rapid reconstitution of a healthy immune system and where patient safety, convenience, accessibility as well as cost and scale will be a differentiating factor. To this end, I'm pleased to announce the clinical expansion of our iPSC product platform into AutoMUNITY. In July, The FDA cleared our IND application for clinical investigation of FT819, Our off the shelf CD19 targeted CAR T cell program in patients with SLE, including for patients with active lupus nephritis or active SLE without renal cell involvement. We have now initiated Phase 1 study start up activities at multiple sites.

Speaker 1

The Phase 1 study in SLE is designed to evaluate the safety, pharmacokinetics, anti B cell activity of a single dose of FT819 administered following a standard conditioning regimen consisting of either CyFlu or bendamustine. Dose escalation will commence at the first dose level of 360,000,000 cells. Importantly, we have previously presented clinical data of a single dose of FT819 At doses up to 360,000,000 cells in the setting of relapsedrefractory B cell lymphoma, where we reported safety and clinical activity. Of the first eleven patients treated with a single dose of the FT819 At up to 360,000,000 cells, we observed a favorable safety profile with no immune effector cell associated neurotoxicity and mild cytokine release syndrome. We observed antitumor activity in heavily pretreated patients, including 3 complete responses.

Speaker 1

And we observed CAR T cell expansion that peaked In the peripheral blood between days 811. The Phase 1 study of FT819 SLE allows for assessment of Higher dose levels, each up to 3 times the highest cleared dose level as well as for the opening of multiple dose expansion cohorts, each of which may be enrolled in parallel. We are pleased to receive a favorable review of our FT819 clinical protocol And the clinical experts of the protocol design committee of Lupus Therapeutics, an affiliate of the Lupus Research Alliance. We also continue to watch with keen interest the emergence of additional clinical data in Autoimmunity, And we are currently evaluating additional clinical expansion opportunities for FT819 as well as for FT-five twenty two, Where we think the potential to reduce conditioning chemotherapy and to target and deplete B cells, plasma cells and auto reactive T cells With an off the shelf ADR arm CD19 targeted CAR NK cell offers a highly differentiated therapeutic profile. We have remained resilient during these challenging times and focused our attention on building a fully integrated operation that leads in the research, Development and manufacture of multiplex engineered iPSC derived cellular immunotherapies.

Speaker 1

As we look towards 2024, we are well positioned to achieve important clinical readouts in oncology and autoimmunity across multiple programs. Clinical activities are now ongoing for our 2 most innovative oncology programs, FT-five twenty two in B cell lymphoma and FTA-two fifty in solid tumors as well as for our 1st autoimmunity program, FTA-nineteen and SLE. We also continue to advance our Phase 1 study of FT819 in B cell malignancies, Where we are enrolling patients in single dose treatment cohorts at 540,000,000 cells in BCL and at 360,000,000 cells in CLO as well as our Phase 1 study of FT596 in multiple myeloma, Well, we are enrolling patients in 3 dose treatment cohorts at 1,000,000,000 cells per dose as monotherapy and in combination with CD38 targeted monoclonal antibody therapy. Finally, our investment in innovation continues, including under our solid tumor collaboration with Ono, as we continue to advance new multiplex engineered Heart T cell programs toward clinical development. We remain confident in our belief that our proprietary iPSC product platform is uniquely suited to create highly differentiated product candidates with the potential to deliver multiple mechanisms of action and therapeutic benefits patients with cancer and autoimmune diseases.

Speaker 1

I'd now like to turn the call over to Ed to review our financial results 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 Q3 were approximately $350,000,000 In the Q3 of this year, our revenue declined to $1,900,000 compared to $15,000,000 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.

Speaker 1

S. And European co development and co commercialization arrangement With Ono for FT825 in the Q4 of last year, we now account for that program's reimbursable expenses as an offset within our research and development costs. We recognized $2,100,000 of contra R and D expense in the quarter. Research and development expenses for the quarter decreased by 57% to $34,300,000 The decrease in our R and D expenses was attributable primarily to a decrease in salaries and benefits, including share based compensation expense following the company's restructuring in the Q1 and from lower clinical trial costs and lower demand for R and D Materials and Equipment. General and administrative expenses for the 3rd quarter decreased by 12% to $18,900,000 The decline in our G and A expenses was attributable primarily to a decrease in salaries and benefits, including share based compensation expense.

Speaker 1

Total operating expenses for the 3rd quarter declined 47% to $53,200,000 which includes $10,100,000 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 1st milestone payment to MSK in 2021. Up to 2 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 Q3, we recorded a non cash $1,000,000 non operating benefit associated with the change in fair value.

Speaker 1

Our net loss for the quarter was $45,200,000 or $0.46 per share. Finally, we reiterate guidance for full year GAAP operating expenses to be in the range of 2.65 to $285,000,000 and that our year end cash and investments will exceed $300,000,000 I would now like to open the call for questions.

Operator

Thank If your question has been answered and you'd like to remove yourself in the queue. Our first question comes from Yigal Nochomovitz with Citi.

Speaker 2

Hi, guys. This is Ashraf Mubarik on for your call. Thanks for taking the questions. I just have a couple. For FT-five twenty two in the Phase 1, I'm just curious if you think if there's 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?

Speaker 2

Or does there really need to be no drop off for you to utilize a preconditioning For your regimen in future studies? Thanks.

Speaker 1

Yes. I don't I think when we look at the data, I think the data is really going Driven by, at the end of the day, patient outcomes and responses, we're definitely interested in understanding the PK profile of F-two thousand five hundred and twenty two with and without Conditioning, and I think that will be help guide dose escalation. But ultimately, I think it's about patient benefit and driving patient benefit Potentially with node conditioning, as that being the important element of 5/22 with respect to its unique profile.

Speaker 2

Okay. Understood. We'll 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 trastuzumabdurastucan given the differences in binding dynamics you showed with Titsi? I'm 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?

Speaker 2

Thanks.

Speaker 1

Yes, absolutely. We've 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 pre clinically 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 FTA-two fifty five and trastuzumab.

Speaker 2

Okay, great. Thanks very much.

Operator

Thank you. Our next question comes from Michael Yee with Jefferies. Your line is open.

Speaker 3

Hi, this is Jenna on for Mike. Thanks for taking our questions. We wanted to get your latest take on the landscape. The CD19 CAR T is moving into earlier lines and there are new players coming to the market, CAR T and going after post CD19. So in the context of all of that, where do you see the next gen CAR NK program CD19 ultimately fit into that landscape.

Speaker 3

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? Thank you.

Speaker 1

Sure. Not going to comment on enrollment other than to reiterate the comments we made on the call where the study is open for enrollment. We've not announced the first patient. The first low conditioning patient, if you will, That patient has could be enrolled as early as patient 4. We are required to clear the first dose level In the conditioning arm before opening the no conditioning arm.

Speaker 1

So first, assuming no DLT, the first three patients would receive conditioning And then 2 events can occur simultaneously. Number 1, you can dose escalate the conditioning arm as well as open the no conditioning arm. And so the 4th patient could be a no conditioning patient. In terms of the landscape, completely agree. It's a super competitive landscape.

Speaker 1

And I think there are I think at the same time, there are multiple opportunities that Can exist for 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 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 be 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 Cells, to plug into standard immunotherapy regimens, for instance, Like in our R CHOP or an earlier line regimen in myeloma, I think those opportunities exist. I think one of the challenges that exist Yes, whether it be autologous or allogeneic cell therapy, is today those regimens bring CyFlu along for the ride.

Speaker 1

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 A side flew. And that's one of the reasons we're very excited about 5/22 and ADR and the potential to reduce significantly reduce the dependency on conditioning and enable a more seamless combination with Standard regimens that are used earlier in care in the community.

Speaker 3

Thank you very much.

Operator

Thank you. Our next question comes from Tyler Van Buren with TD Cowen. Your line is open.

Speaker 2

Hey, guys. As we think about the next 6 to 12 months, what will the 1 or 2 major value creating events be in your view? And What should investors expect from them?

Speaker 1

Yes. I think the 3 that I think are worth Just noting, we're on I highlighted with my comments, I think we have an opportunity to develop to demonstrate proof of concept with FT-five twenty two, including in the no CyFlu regimen. I think that's it can be a pretty game changing If you can deliver cell therapies without conditioning chemotherapy, and essentially for all intents and purposes make A cell therapy looks 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 5/22, it's ADR built in and no side flow. Also very excited about FT-825.

Speaker 1

FTA-two fifty 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 hematologic malignancies. 825 being an 8 pointed edited cell therapy and what I'll just sort of consider to be a fine tuned binding domain against HER2. I think Early on in that study, given that we're starting at 100,000,000 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 of off the shelf cell therapies in solid tumors.

Speaker 1

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 Dana Graybosch with Leerink Partners. Your line is open.

Speaker 3

Yes. I wonder if you could

Operator

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?

Speaker 1

Yes. I think FT819 obviously, and alluded to this, has human clinical experience. I 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.

Speaker 1

And as you know, 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 FT-five twenty two, there is potentially A broader therapeutic appeal, including and especially if the ADR technology allows for reduction or elimination of condition gene chemotherapy, which I think is somewhat of a barrier, obviously, in autoimmunity, certainly more so than in oncology.

Speaker 1

And with FT-five twenty two, as you know, we have the potential to combine with monoclonal antibody therapy. And I think with FT-five twenty two, we're looking at, let's Call it to sort of a broader array of potential autoimmune diseases that we could target given the multiple mechanisms of action That are BIL-eight thousand two hundred and twenty two beyond CD19 targeting. So whether that be, for instance, targeting CD20 with a monoclonal antibody, CD38 with a monoclonal antibody, or potentially even targeting auto reactive 401BB expressing T cells. So I think the FT-five twenty two profile has the FT-five twenty two product candidate has potentially much broader reach than a CD19 targeted cell therapy.

Operator

Great. Thank you. Thank you. Our next question comes from Michael Schmidt with Guggenheim. Your line is open.

Operator

Hey,

Speaker 3

this is Kelsey on for Michael. Thanks for taking our question. I guess Typically for 825 in HER2 solid tumors, I guess, what types of tumors should we 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.

Speaker 1

Yes. I think the efficacy is going to be judged by the particular patients that we will ultimately enroll. There is a fairly broad enrollment Our inclusion criteria in the study, it's not limited to, for instance, HER2, IHC3. So

Operator

Thank you. Our next question comes from Peter Lawson with Barclays. Your line is open.

Speaker 4

Great. Thank you. Scott, thanks for the update. Thanks for taking my questions. Just on your SOVATE tumor programs, circling back on that.

Speaker 4

The learnings from your prior NK cells in solid tumor that kind of rolled over to The current program, what would be learnings there? And then for your HER2 directed T cell, where do you think that would fit in the treatment paradigm?

Speaker 1

Yes. And so I think while we've shared some of the data that we've Seeing in NK cells with solid tumors in the setting of solid tumors, including PAR NK cells, Where with our most recent version of in solid tumors with FT596, which was the clarmic AMITV Product candidate, we certainly saw activity at 100,000,000 cells per dose. So I do think there is Interesting activity that we've demonstrated in the past with off the shelf cell therapies. I think it It would be premature for me to say comment on, gosh, what do we know with respect to an NK cell versus a T cell. I think they're just very different sort of Cellular vehicles, if you will.

Speaker 1

So I don't necessarily think you can extrapolate what we've 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 cells, Especially in the solid tumor setting, and knowing quite honestly all the incremental innovation that's building to 825.

Speaker 4

Got you. And then I guess the follow-up question was just on where you think this HER2 directed T cell would be positioned

Speaker 1

Yes, I think it's too early to comment on that. I think as we look at the HER2 landscape, obviously, What's being demonstrated with the ABCs are pretty remarkable. But I think what we're excited about at the same time is that, again, It is solid tumor settings. Patients are relapsing. There's significant unmet need.

Speaker 1

And I think what we're Excited about as well is there seems to be activity in HER2 expressing tumors That cover a breadth of different types of solid tumors. So I think that we're now seeing HER2 starting to become validated, especially if you're able to target HER2 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 HER2 in the solid tumor space It's significantly expanding.

Speaker 4

Great. Thanks so much.

Operator

Thank you. Our next question comes from Andrea Tan with Goldman Sachs. Your line is open.

Speaker 3

Hello. This is Talani on for Andrea. Thank you for taking our questions. Firstly, for FT819, would you mind just sharing a bit more about the rationale And then secondly, if you could provide a bit more details around the clinical trial design for the Phase 1 study. Thank you.

Speaker 1

Yes. I think the rationale for starting Lupus is there's strong clinical precedent For CD19 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's a dose escalation study. We can treat at multiple escalating doses, Stepping up at 3 times the previously cleared dose level, each dose level each and every dose level that clears DLT We've able to expand and enroll 10 patients in expansion.

Speaker 1

So you can explore multiple different dose levels and multiple different expansions, assuming that that dose level has cleared DLT. We are able to enroll patients with lupus nephritis as well as patients with other organ involvement.

Operator

Thank you. Our next question comes from Yannan Xu with Wells Fargo. Your line is open.

Speaker 5

Great. Thanks for taking our questions. First on the lupus study for FT-eight nineteen, I was wondering, I think you mentioned lymphodepletion regimen is standard. I'm wondering, how does it compare With the German group's lymphodepletion regimen and also if you

Speaker 1

It's exactly the same regimen.

Speaker 5

Great. That's very helpful. Thank you. And another question on FT-five 22. For the no lymphodepletion regimen, I was wondering the 300,000,000 Times 3, that dose regimen as a starting dose, what's your expectation in terms of how much T cells, can that dose remove?

Speaker 5

Do you think 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

Speaker 1

Difficult for me to answer that question today. We're certainly going to prioritize translational data In understanding the differences between the doses, keep in mind that, this is not all about at the end of the day, it's not Really about lymphoconditioning 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 cells. Not all T cells express 4 1BB.

Speaker 1

In fact, only for instance, the allo reactive T cell compartment is the Primary expressor of 401BB. So this is not really a lymphoconditioning approach. It's meant to defend the cell from potential forces of rejection. It's also a receptor. It is a CAR against 41BB.

Speaker 1

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 antitumor activity.

Speaker 5

Got it. That's very helpful. And then lastly, in terms of your Consideration for FT-five twenty two for autoimmune disorders. I was wondering what might be The catalyst that prompt that decision, would it be the observation in this cancer And see how the non lymphodepletion regimen is doing or is it something else? Thank you.

Speaker 1

Yes. I think the 5/22 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 5:22 in autoimmunity that actually would test something very similar to what we're doing in oncology plus or minus side field.

Speaker 5

Got it. Thank you very much.

Operator

Thank you. Our next question comes from Esther Duarte with BMO Capital Markets. Your line is open.

Speaker 6

Great. Thanks for taking the 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 8/19 compares to sort of Some of the emerging data around, other assets that are exploring sort of systemic lupus. Thank you.

Speaker 1

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? Yes.

Speaker 1

So our initial study does attract to that. We've taken Samples from healthy patients or healthy donors, SLE patients and the nephro arthritis patients and we can clearly see Very distinct and specific elimination of the D cell compartment within those three populations. I would also reference you back to Michelle Sadelain, Collaboration publication that we've had about a year ago now in Nature Biomedical Engineering where there's a whole slew of in vitro and in vivo studies Showing the durability of the activity of FT819 in targeting B cell. And then the final thing that we talked The other thing that we've talked to in the past, which we've 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 8 19 oncology study As well as the prior 596 study in oncology, where in some of those patients, we were able to detect B cells In those patients at baseline.

Speaker 1

And we were able to go back and look at, for instance, the kinetics and depth of the cell depletion in patients in oncology receiving 819 and or receiving FT596.

Speaker 6

Thank you for the color.

Operator

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

Speaker 7

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. But and then the other question is, do you think of 819 as a bridge into looking at other Chuck's in autoimmune in the same way you went through that process with NKs.

Speaker 1

Yes. I think it's a little Too early to know. I mean, the field of op 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, in some academic studies, We've seen some pretty remarkable results. I think it's really early for the field.

Speaker 1

And ultimately, what are the Therapeutic requirements that best serve patients and induce long term drug 3 remissions, which I think is the excitement in particular about cell therapies. I think we're all going to learn a lot about that, Quite honestly, in the next 3, 6, 12, 18 months, as we explore at least the first versions of autologous

Speaker 7

And just on the autoimmune study, how many sites are you going to Start in the U. S. Yes.

Speaker 1

We're working through that. I can think one of the strategies quite honestly with respect to that we have heard In speaking with folks in the field is that they 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 8/19 study in oncology in I think somewhere between 12 to Sites are open. And so as we think about how to most effectively get 8 19 off the ground in autoimmunity, We're 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 oncologists and the rheumatologists to treat patients. All right.

Speaker 7

Thanks, Scott. I appreciate it.

Speaker 1

Sure.

Operator

Sure. Thank you. That concludes the question and answer session. I'd like to turn the call back over to Scott Washko

Speaker 1

Hope all of you make it out here for Ash in San Diego and happy to 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.

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Fate Therapeutics Q3 2023
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