Q4 2020 Fate Therapeutics Inc Earnings Call

Welcome to the C therapeutics fourth quarter, 'twenty and 'twenty play natural results conference call. At this time all participants are in a listen only mode and this call is being webcast live on the investors and media section on <unk> website at fate therapeutics.

Operator: Welcome to the Fate Therapeutics 4th Quarter 2020 Financial Results Conference Call. At this time, all participants are in a listen-only mode. This call is being webcast live on the Investors and Media section of Fate's website at www.fatetherapeutics.com. As a reminder, today's call is being recorded. I would now like to introduce Scott Walshko, President and CEO of Fate Therapeutics. The floor is yours

Dot Com as a reminder, today's call is being recorded.

I would now like to introduce Scott <unk>, President and CEO of <unk> therapeutics the floor is yours.

Scott Walshko: Thank you. Good afternoon, and thank you everyone for joining us for the Fate Therapeutics fourth quarter 2020 financial results call. Shortly after 4 p.m. Eastern Time today, we issued a press release with these results, which can be found on the investors section of our website under the press release section. In addition, our Form 10-K for the year ended December 31, 2020, was filed shortly thereafter and can be found on the Investors section of our website under Financial Information.

Thank you.

Good afternoon, and thanks, everyone for joining us for the fate Therapeutics fourth quarter 2020 financial results call. Shortly after four P. M. Eastern time today, we issued a press release with these results, which can be found on the investors section of our website under press releases. In addition, our form 10-K for the year.

Year ended December 31, and 2020 was filed shortly thereafter and can be found on the investors section of our website under financial information.

Scott Walshko: Before we begin, I would like to remind everyone that, except for statements of historical fact, 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.

<unk>, 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 $19 95. These statements involve risks and.

<unk> that can cause actual results to differ materially from those and such forward looking statements.

Scott Walshko: Please see the forward-looking statement disclaimer on the company's earnings press release issued after the close of market today, as well as the risk factors in the company's SEC filings included in our Form 10-K for the year ended December 31, 2020, that was filed with the, 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.

Please see the forward looking statement disclaimer on the company's earnings press release issued after the close of market today as well as the risk factors and the Companys SEC filings included in our form 10-K for the year ended December 31, and 2020 that was filed with the SEC today.

Undue reliance should not be placed on forward looking statements, which speak only as of the day. They are made as the facts and circumstances underlying these forward looking statements may change.

Sept as required by law fate therapeutics disclaims any obligation to update these forward looking statements to reflect future information events or circumstances.

Scott Walshko: Joining me on today's call are Dr. Wayne Hsu, our Senior Vice President of Clinical Development; Ed Dulac, our Chief Financial Officer; Dr. Dan Shumaker, our Chief Scientific Officer; and Dr. Bob Valamehr, our Chief Development Officer. Today, we will review some of the clinical data for our FT-516 and FT-596 programs that we shared at the ASH conference in December, highlight our clinical progress and plans for each of our disease franchises, and discuss our advancement toward clinical development of our next wave of multiplexed engineered IPS-derived cell product candidates for solid tumors.

Joining me on today's call our Doctor Wayne Chu, our senior Vice President of clinical development and do Lark, Our Chief Financial Officer, Dr. Dan Shoemaker, our Chief Scientific Officer and Dr. Bob <unk>, Our Chief Development Officer Today, We will review some of the clinical data for our Ft 516 and <unk>.

T $5 96 programs that we shared at the Ash conference in December.

Highlight our clinical progress and plans for each of our disease franchises and discuss our advancement toward clinical development of our next wave of multiplexed engineered Ips derived cell product candidates for solid tumors.

Scott Walshko: Over the past several years, Fate Therapeutics has pioneered an unprecedented vision for cell therapy, one where the significant limitations of patient and donor-derived cell therapies are overcome through induced pluripotent stem cell technology, clonal master-engineered iPSC lines, and off-the-shelf multiplex-engineered cell products.

Over the past several years fate therapeutics has pioneered and unprecedented vision for cell therapy.

One where the significant limitations of patient and donor derived cell therapies are overcome through induced pluripotent stem cell technology clonal master engineered Ips see lines and off the shelf multiplex engineered cell products.

Scott Walshko: Within the past several months, we have made great strides in delivering on this vision for the benefit of patients with cancer. We have demonstrated that iPSC-derived NK cells can be mass-produced, cryopreserved, and administered off-the-shelf to patients in the outpatient setting. We have demonstrated the clinical safety and the therapeutic activity of engineered iPSC-derived NK cells. We have shown that our off-the-shelf self-product candidates can drive patient responses, including complete responses, and patients with relapsed refractory disease.

Within the past several months, we have made great strides in delivering on this vision for the benefit of patients with cancer.

We have demonstrated that Ips derived NK cells can be mass produced cryo preserved and administer to off the shelf to patients in the outpatient setting.

We have demonstrated the clinical safety and the therapeutic activity of engineered Ips derived NK cells, having shown that are off the shelf cell product candidates can drive patient responses, including complete responses in patients with relapsed refractory disease.

Scott Walshko: We have demonstrated that treatment schedules consisting of multiple doses and multiple cycles of iPS-derived NK cells can be well tolerated without evidence of host rejection, and that patient responses can deepen through additional doses. We have demonstrated that our proprietary, high-affinity, non-cleavable CD16FC receptor, a core functional component used in our IPS-derived NK cell product platform, can effectively synergize with and enhance the mechanism of action of tumor-targeted antibodies.

We have demonstrated that treatment schedules, consisting of multiple doses and multiple cycles of Ips derived NK cells can be well tolerated without evidence of host rejection and that patient responses can deepen through additional dosing.

We have demonstrated that our proprietary high affinity non cleavable CD 16 FC receptor a poor functional component used in our Ips derived NK cell product platform can effectively synergize with and enhance the mechanism of action of tumor targeted antibodies.

Scott Walshko: And we have demonstrated that our IPS-derived NK cell product candidates can be engineered with multiple components of synthetic biology to attack cancer and that we can successfully work with the FDA to bring these first-of-kind multiplexed engineered cell products to patients. We are very encouraged by the clinical progress we have made across our disease areas, and we look forward to a promising year ahead in the disease area of B cell malignancy. We are encouraged by the interim data we reported in December from our Phase 1 study of FT5-16 in combination with rituximab for patients with relapsed refractory B-cell lymphoma.

And we have demonstrated that our Ips derived NK cell product candidates can be engineered with multiple components of synthetic biology to attack cancer.

And that we can successfully work with the FDA to bring these first of kind multiplexed engineered cell products to patients.

We are very encouraged by the clinical progress we have made across our disease areas and we look forward to a promising year ahead.

And the disease area of B cell malignancies, we are encouraged by the interim data we reported in December from our Phase one study of Ft 516 in combination with Rituximab for patients with relapsed refractory b cell lymphoma.

Scott Walshko: As of a November 16, 2020 data cutoff, three of four efficacy-evaluable patients in dose cohorts two and three achieved an objective response, with two patients achieving a complete response. We believe these clinical data are compelling on multiple... All four patients had been treated previously with at least two lines of rituximab-containing regimens, including one patient with diffuse large B-cell lymphoma, who was most recently refrac The outpatient treatment schedule, consisting of two cycles of three weekly doses of FT-5, was well tolerated, and there was clinical evidence to suggest that the second FT-516 treatment cycle conferred clinical benefit.

As of November 16, 2020 data cutoff, three or four efficacy evaluable patients in dose cohorts two and three achieved an objective response with two patients achieving a complete response, we believe these clinical data are compelling on multiple fronts.

All four patients had been treated previously with at least two lines of rituximab containing regimens, including one patient with diffuse large b cell lymphoma, who was most recently refractory to rituximab containing regimen and achieved a complete response following treatment with <unk>.

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The outpatient treatment schedule, consisting of two cycles of three weekly doses of Ft, 516 was well tolerated and there was clinical evidence to suggest that the second ft 516 treatment cycle conferred clinical benefit.

Scott Walshko: One patient who achieved a partial response on an interim assessment following the first FT5-16 treatment cycle achieved a complete response following the second FT5-16 treatment cycle. There were no events of any grade of CRS, neurotox, or GVHD, and there was no evidence of Tier B cell-mediated host rejection.

One patient who achieved a partial response on an interim assessment. Following the first ft 516 treatment cycle achieved a complete response following the second ft 516 treatment cycle.

There were no events of any grade of Crs neuro tox or gvhd and there were no evidence of tier b cell mediated host rejection.

Scott Walshko: Collectively, early clinical activity of FT516 suggests that the product candidate's high affinity non-cleavable CD16 receptor can effectively synergize with rituximab to drive complete responses in patients that have relapsed following or are refractory to rituximab-containing regimens. And the safety profile of FT516 suggests that multiple doses and multiple cycles can be administered in the outpatient setting Dose escalation with FT516 is currently ongoing at 900 million cells per dose, and we are preparing to initiate dose expansion in relapsed refractory B-cell lymphoma upon clearance of this dose.

Collectively early clinical activity of Ft, 516 suggests that the product candidates high affinity non cleavable CD 16 receptor can effectively synergize with rituximab to drive complete responses in patients that have relapsed following or are refractory to rituximab containing regimens.

Yeah.

And the safety profile of Ft, 516 suggests that multiple doses and multiple cycles can be administered and the outpatient setting.

Dose escalation with Ft 516 is currently ongoing at 900 million cells per dose and we are preparing to initiate dose expansion in relapsed refractory b cell lymphoma upon clearance of this dose cohort.

Scott Walshko: In addition, given the safety, activity, and mechanism of action of FT-516, we are currently considering earlier line opportunities for clinical investigation of FT-516 in B-cell lymphoma, where CD20-targeted monoclonal antibody therapy regimens are used as standard of care. At ASH, we are also pleased to share a clinical vignette of the second patient treated in our Phase I study of FT597. The case study described a heavily pre-treated patient with diffuse large B-cell lymphoma who had previously received seven prior treatment regimens and was most recently refractory to an experimental NK cell regimen consisting of CyFlu lymphoconditioning followed by ex vivo expanded donor-derived NK cells, IL-2, plus rituximab.

In addition, given the safety activity and mechanism of action of Ft. 516. We're currently considering earlier line opportunities for clinical investigation of Ft, 516, and B cell lymphoma, where CD 20 targeted monoclonal antibody therapy regimens are used as standard of care.

At Ash, we were also pleased to share our clinical and yet of the second patient treated in our phase one study of F. T 596. The case study described a heavily pretreated patient with diffuse large b cell lymphoma, who had previously received seven prior treatment regimens and was most recently refractory.

Free to and experimental NK cell regimen, consisting of Cy flew lymphoid conditioning, followed by ex vivo expanded donor derived NK cells IL two plus rituximab.

Scott Walshko: The patient was administered a single-dose cycle of 30 million cells of FT596's monotherapy and achieved a partial response at day 30 following administration. However, notably, upon review of the patient's clinical core. The FDA consented to the administration of a second single-dose cycle of FT-596, which was administered on day 47 and resulted in a deepening response as evidenced by further decreases in both tumor size and metabolic activity. No DLTs, no FT-596-related SAEs, and no events of any grade of CRS, ICANS, or GVHD were reported by the investigator.

And the patient was administered a single dose cycle of 30 million cells of ft, 596, as mono therapy and achieved a partial response at day 30 following administration, notably upon review of the patient's clinical course, the FDA consented to administration of a second single dose.

<unk> of <unk> 96, which was administered on day 47 and resulted in a deepening response as evidenced by further decreases in both tumor size and metabolic activity.

No Dlp's no FTE 596 related <unk> and no events of any grade of Crs I cans or gvhd were reported by the investigator.

Scott Walshko: We believe this patient case study is significant in a few... Since FT-596 was administered as a monotherapy, this provides a first clinical demonstration that our proprietary CAR construct optimized for NK cell biology, which contains an NKG2D transmembrane domain, a 2B4 co-stimulatory domain, and a CD3 zeta signaling domain, is active. Additionally, the patient achieved a partial response without any events of any grade of CRS, eye cancer, or GVHD, suggesting that CAR-NK cells may have a differentiated safety profile as compared to CAR-T cells.

We believe this patient case study is significant on a few fronts.

And as Ft, 596 was administered as a mono therapy. This.

This provides our first clinical demonstration that our proprietary car construct optimized for NK cell biology.

Which contains and NK G. Two day transmembrane domain or two before co stimulatory domain and a CD three <unk> signaling domain is active.

Additionally, the patient achieved a partial response without any events of any grade of Crs I cans or gvhd, suggesting that car NK cells may have a differentiated safety profile as compared to car T cells.

Scott Walshko: And the patient's response deepened with a second single-dose cycle of FT5-9, once again underscoring that follow-on doses and cycles of iPS-derived NK cells can be safely administered and confer clinical benefits. On this last point, we are encouraged by the patient's partial response at day 30.

And the patient's response deepened with a second single dose cycle of Ft 596, once again underscoring that follow on doses and cycles of Ips derived NK cells can be safely administered and confer a clinical benefit.

And this last point, we are encouraged by the patients partial response at day 30. However, we continue to believe that relapsed refractory patients with aggressive cancers will be best served by administration of multiple doses. During the first weeks of treatment. It is well documented that adaptively.

Scott Walshko: However, we continue to believe that relapsed refractory patients with aggressive cancers will be best served by the administration of multiple doses during the first weeks of treatment. It is well documented that adoptively transferred NK cells persist for a short duration, that adoptively transferred cells, including CAR T cells, can undergo significant changes in phenotype and function in the days and weeks following administration, and that the critical period for maximal anti-tumor activity is during the first days and weeks following administration. To this end, we plan to submit a protocol amendment to the FDA in the coming weeks to enable multiple dosing of FT596 within the first 30-day treatment cycle.

Transferred NK cells persist for short duration.

That adoptive Lee transferred cells, including car T cells can undergo significant changes and phenotype and function and the days and weeks following administration and that's a critical period for maximal anti tumor activity is during the first days and weeks following administration.

To this and we plan to submit a protocol amendment to the FDA and the coming weeks to enable multiple multi dosing of ft 596 within the first 30 day treatment cycle.

Under the current clinical protocol dose escalation with Ft 596 for the treatment of B cell lymphoma is ongoing in the second dose cohorts of 90 million cells as monotherapy and in combination with Rituximab for multi antigen targeting.

Scott Walshko: Under the current clinical protocol, dose escalation with FT596 for the treatment of B-cell lymphoma is ongoing in the second-dose cohorts of 90 million cells as monotherapy and in combination with rituximab for multi-antigen targeting. Additionally, the first patients with chronic lymphocytic leukemia have been treated in the first dose cohort of 30 million cells as monotherapy. And we plan to begin enrollment in combination with ibinituzumab for multi-antigen targeting upon clearance of the first monotherapy dose.

Additionally, the first patients with chronic lymphocytic leukemia have been treated and the first dose cohort of 30 million cells as monotherapy and we plan to begin enrollment and combination with have been a Tuesday mab from multi antigen targeting upon clearance of the first monotherapy dose cohort.

We also continue to make great progress and pioneering the clinical development of Ips derived car T cells for cancer.

Scott Walshko: We also continue to make great progress in pioneering the clinical development of IPS-derived CAR T-cells for cancer. Last year, we successfully worked with the FDA to clear the first ever IND application for an IPS-derived CAR T-cell product candidate, and we are now preparing to initiate a multi-center Phase I clinical trial for FT819 across three types of B-celled malignant cells. Chronic Lymphocytic Leukemia, Acute Lymphoblastic Leukemia, and B-cell lymphoma.

Last year, we successfully worked with the FDA to clear their first ever IND application for an Ips derived car T cell product candidate and we are now preparing to initiate a multi center phase one clinical trial for F. T 819 across three types of B cell malignancies, chronic lymphocytic leukemia.

Acute lymphoblastic leukemia, and B cell lymphoma.

Scott Walshko: Notably, each disease type will enroll independently, and each indication will evaluate three treatment regimens, single doses of FT-819, single doses of FT-819 plus IL-2 cytokine support, and three fractionated doses of FT-89. In preparation for study initiation, we have completed our first GMP manufacturing run and continue to conduct assay validation and product release testing for FT-819. We also continue to innovate and optimize our manufacturing process, including in our collaborations with Ono and Janssen, and we have initiated a second GMP manufacturing run of FT-819 to implement certain improvements.

Notably each disease type will enroll independently and.

And each indication will evaluate three treatment regimens single dose of eight FTE and 19 single dose of F. T 819, plus IL two cytokine support.

And three fractionated doses of F T 819.

And preparation for study initiation, we have completed our first GMP manufacturing run and continue to conduct assay validation and product release testing for FTA 19.

We also continue to innovate and optimize our manufacturing process, including under our collaborations with Ono and Janssen and we have initiated a second GMP manufacturing run of F. T 819 to implement certain improvements.

Scott Walshko: We expect to treat the first patients with FT-819 in the middle of 2021. AML is our second disease area of interest and one where there is strong clinical precedent for donor-derived NK cell therapy. Most clinical studies in the donor-derived NK cell field, however, have been conducted as single-site, investigator-initiated studies, as patient eligibility has been significantly limited by the requirement to use NK cells that are matched to the patient, that are manufactured solely for that patient, and that are delivered fresh as a single-dose therapy.

We expect to treat the first patients with F T eight and 19.

And the middle of 2021.

AML is our second disease area of interest and one where there is strong clinical precedent for donor derived NK cell therapy, most clinical studies and the donor derived NK cell field. However have been conducted a single site investigator initiated studies as patient eligibility has been.

<unk> eliminated by the requirement to use NK cells that are matched to the patient that are manufactured solely for that patient and.

And that are delivered fresh and as a single dose therapy we've.

Scott Walshko: We believe there is a significant therapeutic opportunity for off-the-shelf NK cell therapy for patients with relapsed refractory AML, one where multiple doses of a cryopreserved NK cell product can be thawed and infused, significantly reducing or eliminating the leukemic burden, enabling patients to qualify for the potentially curative procedure of allogeneic stem cell treatment. In 2020, we Dose escalation with three weekly doses of FT516 is currently ongoing at 900 million cells per dose.

We believe there is a significant therapeutic opportunity for off the shelf NK cell therapy for patients with relapsed refractory AML, one where multiple doses of our cryo preserved NK cell product can be thawed, and infused to significantly reduce or eliminate leukemic burden enabling P.

<unk> to qualify for the potentially curative procedure of allogeneic stem cell transplant.

In 2020, we made strong progress with our ft, 516, and ft $5 38 programs for the treatment of relapsed refractory AML dose escalation with three weekly doses of Ft. 516 is currently ongoing at 900 million cells per dose.

Scott Walshko: Additionally, we successfully worked with the FDA to clear our IND application for FT538, the first ever CRISPR-edited, iPS-derived cell product to advance the clinical investigation in the U.S. FT-538 is our third generation product candidate designed to promote innate immunity and is derived from a clonal master IPSC line uniformly engineered with three functional components, our high-affinity non-cleavable CD16FC receptor, an IL-15 receptor fusion that augments NK cell activity, and the deletion of the CD38 gene, which confers resistance to oxidative stress and prevents fractricide when combined with CD38-targeted monoclonal antibody therapy. Dose escalation with three weekly doses of FT-538 is currently ongoing at 100 million cells per dose for the treatment of relapsed refractory AM.

Additionally, we successfully worked with the FDA to clear our IND application for Ft 538, the first ever CRISPR edited Ips derived cell product to advance the clinical investigation in the U S.

<unk> hundred 38 is our third generation product candidate designed to permit and Nate immunity and is derived from a clonal Master Ips C line uniformly engineered with three functional components are high affinity non cleavable <unk> 16 FC receptor and IL 15 receptors.

Fusion that augments NK cell activity.

And the deletion of the CD, 38, gene, which confers resistance to oxidative stress and prevents fracture side when combined with CD 38 targeted monoclonal antibody therapy.

Dose escalation with three weekly doses of Ft. 538 is currently ongoing at 100 million cells per dose for the treatment of relapsed refractory AML.

At the European Hematology meeting in 2020.

Scott Walshko: At the European Hematology Meeting in 2020, a presentation caught our attention that highlighted the potential therapeutic role of CD38-targeted monoclonal antibody therapy in treating elderly patients with AML. An assessment of bone marrow samples from newly diagnosed elderly AML patients showed CD38 expression on leukemic blasts in 239 out of 241 samples tested, strongly indicating the potential of CD38 as a therapeutic target for AML.

Presentation caught our attention that highlighted the potential therapeutic role of CD 38 targeted monoclonal antibody therapy in treating elderly patients with AML.

And assessment of bone marrow samples from newly diagnosed elderly AML patients showed CD 38 expression on leukemic blasts in 239 out of 241 samples tested.

Strongly indicating the potential of CD 38, as a therapeutic target for AML.

Scott Walshko: To exploit this potential and to promote NK cell-mediated ADCC, we are assessing FT538 in combination with Dara2Met, an FDA-approved CD38-targeted monoclonal antibody therapy. The Phase I Clinical Trial, which is sponsored and managed by investigators from the Masonic Cancer Center, University of Minnesota, is designed to assess three weekly doses of FT538 in combination with daratumab in patients with relapse We expect this trial to start in mid-2021.

To exploit this potential and to promote NK cell mediated ADC, we are assessing ft $5 38 in combination with Dara two mab and FDA approved CD 38 targeted monoclonal antibody therapy. The phase one clinical trial, which is sponsored and managed by investigators from the.

Masonic Cancer Center University of Minnesota is designed to assess three weekly doses of <unk> $5 38 in combination with Dara, two mab and patients with relapsed refractory AML.

We expect this trial to initiate in mid 2021.

Our third disease area of interest as multiple myeloma and we are very excited about our potential to generate compelling clinical data over the next 12 months with both our FTE $5 38, and F T five seven and six programs.

Scott Walshko: Our third disease area of interest is multiple myeloma, and we are very excited about our potential to generate compelling clinical data over the next 12 months with both our FT538 and FT576 programs. In December, the FDA approved our IND application for FT576, the first ever cell therapy to incorporate four functional anti-tumor components, including a CAR-targeting B-cell maturation. Importantly, our BCMA binding domain is novel, and in preclinical studies, it has shown greater killing of target cells with low expression levels of BCMA in comparison to other BCMA binding domains.

In December and the FDA allowed our IND application for Ft, five seven and six the first ever cell therapy to incorporate for functional anti tumor components, including a car targeting b cell maturation antigen and importantly, our bcm a binding domain is novel and and <unk>.

Preclinical studies and has shown greater killing of target cells with low expression levels of <unk>.

In comparison to other be CMA binding domains, but.

Scott Walshko: The clinical protocol for our Phase I clinical trial of FT576 includes dose escalation, both as monotherapy and in combination with Daratumab, to enable dual antigen targeting of BCMA and CD38 on myeloma cells, an approach that we believe is highly differentiated and holds best in class.

The clinical protocol for our phase one clinical trial with Ft, five seven and six includes dose escalation, both as a monotherapy and in combination with Dara two mab.

To enable dual antigen targeting of the CMA and CD 38 on myeloma cells and approach that we believe is highly differentiated and holds best in class potential.

Scott Walshko: Additionally, the protocol includes assessment of both single-dose and multi-dose treatment regimens to maximize the therapeutic index during the first 30 days following injury. Similar to our approach in lymphoma, we are beginning clinical investigation of multiple myeloma by leveraging our high affinity non-cleavable CD16 receptor, and we are combining FT-538 with Daratumab to maximize ADC. While Daratumab effectively targets CD38 expressed on multiple myeloma cells and induces cell death, it also induces NK cell fracture, which may impair the effectiveness of ADC.

Additionally, the protocol includes incessant of both single dose and multi dose treatment regimens to maximize the therapeutic index. During the first 30 days following infusion.

Similar to our approach and lymphoma, we are beginning clinical investigation of multiple myeloma by leveraging our high affinity non cleavable CD 16 receptor.

And we are combining ft 538, with Dara two mab to maximize ADC.

While Dara two mab effectively targets CD 38 expressed on multiple myeloma cells and induces cell death. It also induces NK cell fratricide, which may impair the effectiveness of ADC.

Scott Walshko: In addition, NK cell function is often impaired in patients with multiple myeloma, further reducing the potential therapeutic activity of daratum. However, collectively, preclinical and clinical observations suggest a potential therapeutic benefit of maintaining NK cell numbers and function. In the second quarter, we expect to initiate enrollment of FT538 in combination with daratumab in the first dose cohort of three weekly doses of 100 million cells for patients with relapsed refractory multiple myeloma who have failed at least two lines of therapy. Over the next 12 months, we plan to substantially increase our clinical investigation in the area of solitude.

In addition, NK cell function is often impaired and patients with multiple myeloma further reducing the potential therapeutic activity of Dar to map.

And collectively preclinical and clinical observations suggest a potential therapeutic benefit of maintaining NK cell numbers and function and.

And the second quarter, we expect to initiate enrollment of ft, $5 38, and combination with Dara to Mam and the first dose cohort of three weekly doses of 100 million cells for patients with relapsed refractory multiple myeloma, who have failed at least two lines of therapy.

Over the next 12 months, we plan to substantially increase our clinical investigation and the area of solid tumors were certainly enthusiastic about the therapeutic potential of NK cells to address significant unmet needs across a wide range of solid tumors and we are pursuing multiple avenues of invest.

Scott Walshko: We're certainly enthusiastic about the therapeutic potential of NK cells to address significant unmet needs across a wide range of solid tumors, and we are pursuing multiple avenues of investigation for clinical benefit. Since NK cells have the innate ability to recognize and directly kill cancer cells that lack MHC class 1 antigen presentation, we believe NK cells may play a unique role in attacking tumors that have evaded T cells and are resistant to checkpoint inhibitor therapy.

Negation for clinical benefit.

Since NK cells have the innate ability to recognize and directly kill cancer cells that lack MHC class. One antigen presentation. We believe NK cells may play a unique role and attacking tumors that have a dated T cells and are resistant to checkpoint inhibitor therapy.

Scott Walshko: We are currently enrolling patients with non-small cell lung cancer or classical Hodgkin's lymphoma who are refractory to or who have relapsed on checkpoint inhibitor therapy. We intend to treat up to 15 patients, administering up to six doses of FT500 at 300 million cells per dose, each with IL-2 cytokine support in combination with the checkpoint inhibitor on which the patient failed or relapsed.

We are currently enrolling the dose expansion stage of the Ft 500 phase one clinical trial for patients with non small cell lung cancer or classical Hodgkin's lymphoma, who are refractory to or who have relapsed on checkpoint inhibitor therapy, we intend to treat up to 15 patients administering up to six.

<unk> doses of Ft, 500 at 300 million cells per dose each with IL two cytokine support in combination with the checkpoint inhibitor on which the patient failed or relapsed.

Scott Walshko: Additionally, we are leveraging our high-affinity non-cleavable CD16 receptor in combination with FDA-approved monoclonal antibodies to promote ADC for solid tissue. We are currently enrolling patients in the second dose cohort of our phase one study of FT-516 in combination with Velumax and ADCC-competent anti-PD-L1 checkpoint inhibitor therapy. We are also actively considering additional settings to exploit the broad potential of ADC, including with FT538 and other tumor-targeting antibodies in solid. Finally, we believe our IPSC product platform represents the ideal framework for designing and developing multiplexed engineered CAR and K-cell product canons.

Additionally, we are leveraging our highest bin and the <unk> CD 16 receptor and combination with FDA approved monoclonal antibodies to promote ADC for solid tumors.

We are currently enrolling patients in the second dose cohort of our phase one study of Ft, 516, and combination with the value Mab and ADC competent anti PDL one checkpoint inhibitor therapy. We are also actively considering additional settings to exploit the broad potential of ADC.

And <unk>, including with Ft, 538, and other tumor targeting antibodies and solid tumors.

And finally, we believe our Ips C product platform represents the ideal framework for designing and developing multiplexed engineered car NK cell product candidates and we currently have four novel Ips derived car NK cell programs for solid tumors undergoing.

Scott Walshko: And we currently have four novel IPS-derived CAR and K-cell programs for solid tumors undergoing preclinical development. These programs include three wholly owned programs and one program under our collaboration with Janssen. During 2021, we expect to submit an IND for FT536.

Preclinical development.

These programs include three wholly owned programs and one program under our collaboration with Janssen.

During 2021, we expect to submit an IND for Ft 536, our proprietary car NK cell program targeting the alpha three domain of the pan tumor associated stress antigens MC game Mcbee.

Scott Walshko: Our proprietary CAR and K-Cell program targeting the Alpha-3 domain of the pan-tumor-associated stress antigens MYC-A and MYC-B, as well as for FT562. Our first CAR and K-Cell program targeting an undisclosed antigen under our collaboration with, And finally, I want to take a moment to note that data on the primary and secondary endpoints in our randomized, controlled, and double-blinded Phase 2 PROTECT clinical trial of protamine are scheduled to be available in the second quarter of 2021.

As well as for F T 562.

Our first car NK cell program targeting and undisclosed antigen under our collaboration with Janssen.

And finally I want to take a moment to note that data on the primary and secondary endpoints and are randomized controlled and double blinded phase II protect clinical trial with protamine and are scheduled to be available in the second quarter of 2021.

Scott Walshko: Protoimmune is our investigational next-generation donor-derived cell graft for patients with hematologic malignancies undergoing allogeneic mobilized peripheral blood transplants. The primary efficacy endpoint of PROTECT is cumulative incidence of grades 2 through 4 acute GVHD by day 100, where clinical studies have shown that up to 60% of patients undergoing matched unrelated donor transplant experience grade 2 through 4 acute GVHD. The second efficacy endpoint of PROTECT is the proportion of subjects alive, without relapse, and without moderate or severe chronic GVHD or GRFS by day three, where clinical studies have shown that only about 20% of patients successfully achieved GVHD-free, relapse-free survival at one year. I would now like to turn the call over to Ed to highlight our fourth quarter financial results.

Protamine is our investigational next generation donor derived cell graft for patients with hematologic malignancies undergoing allogeneic mobilized peripheral blood transplant.

The primary efficacy endpoint of protect is cumulative incidents of grade two through four acute gvhd by day 100, where clinical studies have shown that up to 60% of patients undergoing matched unrelated donor transplant experienced grade two through four acute gvhd.

The second.

Efficacy endpoint and protect is the proportion of subjects alive.

Without relapse and without moderate or severe chronic gvhd or G. RFS by day, three 665, where clinical studies have shown that only about 20% of patients successfully achieve gvhd free relapse free survival at <unk>.

One year.

The statistical analysis plan is designed to independently assess both primary and secondary endpoints and.

I would now like to turn the call over to Ed to highlight our fourth quarter financial results.

Edward J. Dulac: Thank you, Scott. Turning to our financial results, revenue was $15.9 million for the fourth quarter of 2020, compared to $2.8 million for the same period last year. Revenue in the current quarter was derived from our collaborations with Janssen and Ono Pharmaceuticals. In December, we shared with Ono a preclinical data package for an IPSC-derived CAR-T cell product candidate, incorporating Ono's proprietary antigen binding domain, targeting a cancer-specific antigen expressed on certain solid tumors.

Thank you Scott.

Turning to our financial results revenue was $15 $9 million for the fourth quarter of 2020 compared to $2 $8 million for the same period last year.

Revenue and the current quarter was derived from our collaborations with Janssen and Ono pharmaceutical.

In December we shared with Ono, a preclinical data package for an Ips derived car T cell product candidate incorporating <unk> proprietary antigen binding domain and targeting a cancer specific antigen expressed on certain solid tumors.

Based on these data <unk> elected to continue preclinical development of the product candidate under the collaboration and we received a $10 million milestone fee from Ono.

Edward J. Dulac: Based on these data, Ono elected to continue preclinical development of the product candidate under the collaboration, and we received a $10 million milestone fee from Ono. As a reminder, ONO maintains an option to develop and commercialize the IPSC-derived CAR T-cell product candidate in all territories of the world, and we retain the right to co-develop and co-commercialize the product candidate in the United States and Europe under a joint arrangement where we are eligible to share at least 50% of the profits and losses.

As a reminder, Ono maintains an option to develop and commercialize the Ips derived car T cell product candidate and all territories of the world and we retain the right to co develop and co commercialize the product candidate and the United States and Europe under a joint arrangement, where we are eligible.

And to share at least 50% of our profits and losses.

Edward J. Dulac: In the fourth quarter, we recognized $6.1 million of the $10 million milestone payment received from ONO. Research and development expenses for the fourth quarter of 2020 were $39 million, compared to $25.2 million for the same period last year. The increase in R&D expenses was attributable primarily to an increase in employee headcount and compensation, including share-based compensation, and in expenses associated with the facility lease for our new corporate headquarters. General and administrative expenses for the fourth quarter of 2020 were $10.3 million, compared to $6.7 million for the same period last year. The increase in our G&A expenses was attributable primarily to an increase in headcount and employee compensation, including share-based compensation.

And the fourth quarter, we recognized $6 $1 million of the $10 million milestone payment received from Ono.

Research and development expenses for the fourth quarter of 2020 or $39 million compared to $25 $2 million for the same period last year.

The increase in R&D expenses was attributable primarily to an increase and employee head count and compensation, including share based compensation and and expenses associated with the facility lease for our new corporate headquarters.

General and administrative expenses for the fourth quarter of 2020 were $10 $3 million compared to $6 $7 million for the same period last year.

The increase and our G&A expenses was attributable primarily to an increase and head count and employee compensation, including share based compensation.

Edward J. Dulac: Total operating expenses for the fourth quarter of 2020 were $40.5 million, net of $8.8 million in non-cash, share-based compensation expense. In the fourth quarter, we recorded a non-cash, $20.1 million non-operating expense associated with the fair value of contingent milestone payments under our IPSC-derived CAR T-cell collaboration with Memorial Sloan Kettering. In the event that a certain clinical milestone is achieved with an IPSC-derived CAR T-cell product candidate, up to three milestone payments may be owed to MSK based on the subsequent trading values of the company's common stock, ranging from 50 to $150 per share.

Total operating expenses for the fourth quarter of 2020 or $45 million net of $8 $8 million and noncash share based compensation expense.

In the fourth quarter, we recorded a noncash $21 million non operating expense associated with the fair value of contingent milestone payments under our Ips derived car T cell collaboration with Memorial Sloan Kettering.

In the event a certain clinical milestone is achieved with an Ips derived car T cell product candidate and up to three milestone payments may be owed to M. S. K based on subsequent trading values of the company's common stock ranging from 50 to $150 per share.

These milestone payments and the aggregate total up to $75 million and no amounts have been paid or are currently owed to M. S. K.

Edward J. Dulac: These milestone payments, in the aggregate, total up to $75 million, and no amounts have been paid or are currently owed to MSK. We will re-measure this liability, currently valued in the aggregate at $47.7 million, on a quarterly basis, and changes in the fair value will be recorded in our earnings as a non-operating income or expense.

We will re measure of this liability currently valued in the aggregate at $47 $7 million on a quarterly basis and changes and the fair value will be recorded in our earnings as a non operating income or expense.

The company ended the fourth quarter of 2020 with $483 million of cash cash equivalents and investments.

Edward J. Dulac: The company ended the fourth quarter of 2020 with $483 million of cash, cash equivalents, and investments. This does not include the aggregate net proceeds of approximately $432 million received from our January 2021 public equity offering. Common Stock outstanding is 88 million shares, and preferred convertible stock outstanding is 2.8 million shares, each of which is convertible into five shares of common stock under certain conditions. The common stock balance does not include the 5.1 million common shares issued as part of our January 2021 public equity offering. I would now like to open the call to questions.

This does not include the aggregate net proceeds of approximately $432 million received from our January 2021 public equity offering.

Common stock outstanding was 88 million shares and preferred convertible stock outstanding was $2 8 million shares each of which is convertible into five shares of common stock under certain conditions.

The common stock balance does not include the $5 1 million common shares issued as part of our January 2021 public equity offering.

I would now like to open the call to questions.

As a reminder to ask a question and you will need to pass star one on your telephone.

Operator: As a reminder, to ask a question, you will need to press star 1 on your telephone. Your first question comes from the line of Robin Karnakoskas from Trout Securities.

Your first question comes from the line of Robyn kind of class guys from <unk> Securities. Your line is now open.

Krippon: Your line is now open. Hey guys, this is Krippon on behalf of Robin. Thank you so much for taking my call and congratulations on all the progress. One question I had was, in addition to your partnerships with Ono and Johnson, what is your strategy and bandwidth for any additional potential partnerships, and especially those that include your wholly owned product? And then for, sorry, go ahead.

Yeah.

Hey, guys. This is coupon for Robyn. Thank you so much for taking my call and congratulations and all the progress.

One question I had was in addition to your partnerships with <unk> and Janssen.

What is your strategy and bandwidth for any additional potential partnerships and.

And.

Firstly does that include.

Your wholly owned.

<unk> products.

And then share sorry go ahead.

Scott Walshko: Sure, happy to answer that. I think we absolutely have a platform that is amenable, and we have bandwidth to do additional partnerships as well as increase the existing partnerships if we choose to do so.

Sure happy to answer that I think we absolutely have a platform that is amenable and we have bandwidth to do additional partnerships as well as increase the existing partnerships. If we chose to do so.

Great.

Scott Walshko: And then you have, you plan to start, initiate an AML program with FT-538. Would you need to see data from the monotherapy trial before you initiate the combo, or can they be run in parallel? And also, it seems like you're continuing to enroll patients in the FT-516 trial for AML. Can you maybe talk about your overall strategy for AML?

And then you have your plan to initiate and AML program with Ft, 538, and would you need to see data from the monotherapy.

And trial before you initiate the combo or can they be run in parallel and also it seems like you're continuing to enroll patients in the ft 516 trial for and.

Can you maybe talk about your overall strategy and ammo.

Scott Walshko: Sure, I think long-term, so I'll start with long-term vision, long-term vision for AML. I think at the end of the day, we are very interested in targeted strategies for AML.

Sure I think long and so I'll start long term vision long term vision and AML I think at the end of the day, we are very interested and targeted strategies for AML certainly.

Scott Walshko: Certainly.

Scott Walshko: Historically, non-engineered, donor-derived NK cells have shown activity. I think in about 20 to 25 percent of patients, donor-derived NK cells, again, not engineered, not targeted in any express way, have been able to drive responses. But I do think there's significant room for improvement, just like we've seen in other hematologic malignancies, and so the long-term strategy for AML, I think, would be to absolutely have a targeted approach. It was one of the reasons we were really intrigued by the data that we saw at EHA with respect to CD38 expression on leukemic blasts and, potentially, which we're now doing, combining FT538 with daratumab in AML as a first means of looking at a targeted strategy.

Historically non engineered donor derived NK cells have shown activity I think and about 20% to 25% of patients donor derived NK cells again, not engineered not targeted and any expressway have been able to drive responses, but I do think there's significant room for improvement just like we have.

Scene, and other hematologic malignancies, and so the long term strategy and AML I think with two would be to absolutely have a targeted approach and it was one of the reasons. We were really intrigued by the data that we saw at <unk> with respect to CD 38 expression on leukemic blasts and potentially on which we're now doing.

Combining ft $5 38, with Dara two mab in AML as a first means of looking at a targeted strategy.

Great. Thank you so much.

Scott Walshko: Great. Thank you so much. Sure. Your next question comes from the line of Alethea Young from Kantor. Your line is now open.

Sure.

Your next question comes from the line of Elite J Young from Cantor. Your line is now open.

Hey, guys. Thanks for taking my question and certainly been exciting past three or four months.

Andrea R. Tan: Hey guys, thanks for taking my question. Certainly, it's been an exciting past three or four months. I just wanted to kind of go back to the notion of redosing and the conditioning regimens you've used. We've got a couple questions, I think, you know, recently around how viable it might be to use a conditioning regimen, you know, kind of if you had to do it, you had to dose a couple times. And maybe the second part of that question is, are you considering maybe a lighter version of a conditioning regimen? I mean, so far, the profile has seemed pretty benign as far as the drug itself is concerned.

And I just wanted to kind of go back to the notion of re dosing and the conditioning regimen and D views and got a couple of questions I think.

And certainly around how viable it might be that you have a conditioning regimen.

And you know kind of if you had to do it and you got to do a couple of times and and maybe the second part of that question is.

Are you considering maybe a lighter version and have a conditioning regimen and so far the profile and seemed pretty pretty benign as far as it dragged himself book.

Sure. Thank you Wayne and <unk>.

Scott Walshko: Sure, thank you. Wayne and I are not in the same room. Wayne, are you there? I'm here.

Wayne Wayne and Iron out and the same room Wayne or are you. There you want to address here yes.

Wayne Hsu: , , , , , , , , , , , , , ,

Wayne Hsu: Yeah, sure. That's a great question.

Yes sure.

That's a great question. Thank you for asking I think that one of the fundamental questions for our clinical programs and I don't speak just for the fate portfolio, but I would say all sponsors are developing the cellular therapies is really defining the nature of the conditioning regimen and we can.

Wayne Hsu: Thank you for asking. I think that one of the fundamental questions, you know, for our clinical programs, and I don't speak just for the FATE portfolio, but I would say all sponsors that are developing these cellular therapies, is really defining the nature

Currently.

Utilizing the combinations of Fludarabine and cyclophosphamide across our trials.

Wayne Hsu: https://www.youtube.com So, I think one of the things that we're trying to understand, you know, with our current slate of trials is directly addressing the question you raised around what is the tolerability, you know, of a patient to receive potentially multiple rounds of a condition that consists of fludarabine and cyclophosphate. And I think it's probably worth mentioning the fact that the combination of fludarabine For example, in patients who are newly diagnosed with chronic lymphocytic leukemia, one of the more common immunochemotherapy regimens is the combination of rituximab with flu and PSY.

I should note that there are some differences with respect to the schedule and the doses that we're using depending on the indication being tested.

So I think one of the things that we're trying to understand with our current slate of trials and is directly addressing the question you raised around what is the tolerability.

And the patient to receive and potentially multiple rounds of condition that consist of fludarabine and cyclophosphamide and I think it's probably worth mentioning the fact that debt.

The combination of food site does have clinical precedent.

For example, and patients who are newly diagnosed with chronic lymphocytic leukemia, one of the more common immuno chemotherapy regimens as the combination of rituxan that with flu and Si and so there is some clinical precedent to the idea of being able to give multiple rounds of fluids side containing regimen, but.

Wayne Hsu: And so there is some clinical precedent to the idea of being able to give multiple rounds of flu-PSY-containing regimens. But I think an important question, which we plan to address as part of our ongoing studies, is whether or not things like dose adjustments to the fluid aerobic and cyclophosisphamide dose are feasible, not only from a patient safety and tolerability perspective but also with respect to their ability to support the pharmacokinetic profile of our product candidates.

And an important question, which we plan to address as part of our ongoing studies is to see whether or not.

Things like dose adjustment to the food Irving and cyclophosphamide dose.

Our are feasible not only from a patient safety and Tolerability perspective, but also with respect to their ability to support art. The pharmacokinetic profile of our product candidates. We are also very interested and understanding whether or not other combinations of therapies.

Wayne Hsu: We are also, you know, very interested in understanding whether or not other combinations of therapies can be used as conditioning, such that we're not necessarily wed to a paradigm that involves fluid therapy and cyclophosisphamide conditioning. And those ideas are all on the table, and we hope to include initial clinical experiments to address that question in the not-too-distant future as part of our current study.

Can be used as conditioning such.

Such that we're not necessarily wedded to a paradigm that involves fludarabine and cyclophosphamide conditioning and those ideas are all being on the table and we hope to include initial clinical experiments.

The address that question and and not too distant future as part of our current study.

Wayne Hsu: Thanks, Wayne. Your next question comes from the line of Michael Smith from Guggenheim. Your line is now open.

Thanks, Helane great. Thank you.

Your next question comes from the line of Michael Schmidt from Guggenheim. Your line is now open.

Michael Smith: Hey guys, thanks for taking my question. I had two actually, one bigger picture question around pipeline strategy. Obviously, your NK, your engineered NK cell pipeline is much more extensive than your CAR T program at this point. I was just wondering, longer term, how you think the fate portfolio may evolve. And will it be maybe more NK cell centric as opposed to the CAR T focus? So that's my first question and then I have a follow-up.

Hey, guys. Thanks for taking my question.

Had two actually one bigger picture question around pipeline strategy, obviously, you're.

And K engineered NK cell pipeline is much more expensive than your car T program. At this point I was just wondering longer term how you think.

Faith portfolio may evolve and while it would be maybe more NK cell and trade as opposed to car T focus. So that's my first question and I had a follow up.

Scott Walshko: Sure. I can start with that.

Sure I can start with that I mean, obviously you've.

Scott Walshko: I mean, obviously, you're well aware of the history of the company, and we certainly got a head start with NK cells as compared to T cells. But there's a long history of using iPS cell technology to derive T cells, which quite honestly started with our collaborator at Memorial Sloan Kettering, Michel Satellin. And initially, he was able to develop gamma delta T cells and publish on that probably, you know, around 2015.

You're well aware of the history of the company and we certainly got a head start with NK cells as compared to T cells.

And there's a long history and of using Ips cell technology to drive T cells, which quite honestly started with our collaborator and memorial Sloan Kettering Michelle satellite and initially he was able to develop gamma Delta T cells and published on that I wanted to say probably around 2015, our collaboration with him was expressly and.

Scott Walshko: Our collaboration with him was expressly around making alpha beta T cells, and we think, you know, we've actually nailed that quite well and are really excited about advancing 819 into clinical development this year. I would sort of underscore, yes, we are absolutely more advanced on NK cells, and we are pushing very hard with respect to the NK cell side of our pipeline, and are quite honestly super excited, but let's also acknowledge that there's been some really exciting and Patient Responses that have been generated with T-Cell.

Round, making alpha beta T cells, and we think we've we've actually nailed that quite well and are really excited about advancing 819 into clinical development. This year I would I would sort of underscore.

Yes, we are absolutely more advanced one NK cells, and we are pushing very hard with respect to the NK cell side of our pipeline and our and are quite honestly super excited about what we're seeing.

<unk>.

Yeah.

But let's let's also acknowledge that there's been some really exciting results and patient responses that have been generated with T cells, and our collaboration including our own O collaboration and our Janssen collaboration do involve the development.

Scott Walshko: And our collaborations, including our ONO collaboration and our Janssen collaboration, do involve the development of an IPS-derived CAR T-cell canon. So, I would say that while, for instance, our NK cell pipeline is more mature, I would not take that as an indication that we are significantly betting on an NK cell approach over a T cell approach. We are absolutely developing both cell types aggressively.

The Ips derived car T cell candidates.

So I would say that while for instance, our NK cell pipeline as murmured sure I would not take that as an indication that we were we are.

Significantly betting on and NK cell approach over a T cell approach, we are absolutely developing both cell types of aggressively.

Scott Walshko: Great, thanks. And then there is a question on 5.1.6 specifically.

Great. Thanks, and then a question on five one sales specifically you did mention that you are now planning the first expansion cohort and <unk> and I was just wondering around the dosing paradigm I know you've talked about giving.

Scott Walshko: You did mention that you're now planning the first expansion cohort in DLBCL, and I was just wondering about the dosing paradigm. I know you've talked about giving multiple doses over time, et cetera. You know, at the same time, you have already seen deep and good responses after only giving one or two cycles in the dose escalation phase. So I was just wondering how you're thinking about the dosing paradigm in this expansion cohort. Will this be a fixed cycle or fixed time duration dosing paradigm, or will

Giving multiple doses over time et cetera.

At the same time you have seen.

Already deep and good responses after only giving one or two cycle and and the dose escalation and so I was just wondering how you're thinking about.

But the dosing paradigm and this expansion cohort will this be a fixed cycle, a fixed time duration dosing paradigm or will it be a chronic regimen and walk into and a monoclonal antibody therapy.

Scott Walshko: Yeah, so great question. I think what you will see us do as part of dose expansion is continue with where we have seen success. And so we will likely kick off a dose expansion that includes the existing treatment paradigm with FT56. But at the same time, you should not be surprised if we also experiment with other treatment cycles with FT-516, which may involve, for instance, we were just discussing CyFlu, it may involve less CyFlu, it may involve a conditioning regimen that is not CyFlu, and it may involve longer duration of dosing of But there will at least be a core arm of dose expansion that involves the existing treatment paradigm where we are seeing and are excited by the responses.

Yeah. So great question I think what you will see us do as part of dose expansion is continue with where we have seen success.

So we will likely kick off a dose expansion that includes the existing treatment paradigm with ft 516 apt.

At the same time, you should not be surprised if we also experiment with other treatments cycles.

And for with Ft, 516, which may involve for instance, we were just discussing psi fluid may involve less high flu. It may involve the conditioning regimen that is not by flu and it may involve longer duration of dosing of ft 516.

But there will at least be a core arm of dose expansion that involves the existing treatment paradigm, where we are seeing and are excited by the responses.

Scott Walshko: Great. Thank you. Sure. Next is from Yigal Nochomovitz from Citi. Your line is now open. Great. Hi Scott. Thanks for taking the questions.

Great. Thank you.

Sure.

Next is from Aegon and that some of it's from Citi. Your line is now open.

Hi, Scott Thanks for taking my questions I had on us.

Yigal Dov Nochomovitz: Thank you so much. On your myeloma franchise strategy, obviously, you have two programs for myeloma in combo with daratumumab, F538 and FT576, so can you talk about the development strategy there? Are you prepared to advance both combo regimens into later stage trials, or is your objective to settle on one darot combo after you're done with phase one?

On your myeloma franchise strategy, obviously has two programs for myeloma and combo therapy.

And.

Seven six so can you talk about the development strategy. There are you prepared to advance both combo regimens and for later stage trials or is your objective to settle on one day or a combo. After after you're done with phase one.

Yes, it's a great question I think it's too early for us to say, what our long term strategy as necessarily I mean, we have to see sort of what the profiles of both product candidates are.

Scott Walshko: Yeah, it's a great question. I think it's too early for us to say what our long-term strategy is. I mean, we have to see sort of what the profiles of both product candidates are. You know, obviously, we are really encouraged by, if you go to the lymphoma side, we're super encouraged by what we're seeing with FT-516, and we're pushing FT-516 aggressively forward, even though we have FT-596, and we're excited by FT-596.

Obviously, we are really encouraged by if you go to the lymphoma side, we're super encouraged what we're seeing with Ft, 516, and were pushing ft 516 aggressively forward, even though we have ft 596, and we're excited by Ft 596, there may be opportunities for both programs in different lines of treatment, absolutely and I.

Scott Walshko: There may be opportunities for both programs in different lines of treatment, absolutely, and I think we're approaching myeloma from that same perspective, that we're very open-minded. We're going to let the data guide us, the clinical data guide us as to, you know, the potential for the product. You know, generally, I will still continue to say, I do think multi-antigen targeting offers best-in-class potential. But obviously, you know, that needs to play out in the clinic, and there are very few multi-targeted programs in clinical development of any kind, whether IPS-derived or patient or donor-derived.

I think we're approaching myeloma from that same perspective that we're very open minded we're going to let the data guide us the clinical data guide us as to.

And the potential for the product candidates.

Generally I will still continue to say I mean, I do think multi antigen targeting offers best in class potential, but obviously you know that needs to play out in the clinic and there's very few multi program multi targeted programs in clinical development of any kind, whether ips derived or.

Patient or donor derived.

Got it but I would say today I would say today I mean, certainly our confidence has been significantly bolstered and our proprietary CD 16 receptor and its ability to promote ADC with monoclonal antibody therapy.

Scott Walshko: got it

Scott Walshko: But I would say today, I would say today, I mean certainly our confidence has been significantly bolstered in our proprietary CD16 receptor and its ability to promote ADCC with monoclonal antibody therapy.

Okay. Thanks, and then and then turning to the AML.

Scott Walshko: Okay, thanks. And then turning to AML, the EHA data that you mentioned, the 239 and the 241 expressing CD38, are obviously very interesting. Is it a fair assumption, therefore, that for this combo study that you've announced, the 538 plus DARA, that you're not going to do any screening for CD38? You're just going to take AML patients?

And the EAA chain data that you mentioned, the $2 39, and $2 one expressing CD 30, and it's obviously very interesting and the.

Our assumption and therefore, the combo study and announced the fire from April.

Youre not going to do any screening procedure 38 interest from that and you're just going to take take AML patients.

Scott Walshko: That's correct. We're not screening for CD38 in advance, but obviously, in getting bone marrow biopsies, we'll be able to assess for that.

That's true that's correct, we're not screening for CD 38 in advance, but obviously in getting bone marrow biopsies, we'll be able to assess for that.

Scott Walshko: Okay, and then.

Okay and then just one question on your on your preclinical program and the <unk> seven and eight three.

Bahram Valamehr: And then just one question about your preclinical program. On CAR-V7H3, is it the correct expectation that the multiplex engineering is gonna include the high affinity non-cleavable CD16 and the IL-15 receptor fusion? And are there other functionalities beyond those two that you might be developing for this program?

And at the correct expectation multiplex engineering is going to include the high affinity non cleavable <unk> 16, and the IL 15 receptor fusion and are there other functionality is beyond those two that you might be telephone from this program.

Bahram Valamehr: Sure, I'll let Bob answer that question, but before I turn it over to Bob, because I know Bob will talk about all the unique features we are putting into the product candidate, let's keep it to what we've publicly disclosed.

Sure I'll, let Bob answer that question, but before I turn it over to Bob because I know Bob will talk about all the unique features we are putting into the product candidate, let's keep it to what we've publicly disclosed.

Bahram Valamehr: Sure thing, Scott, and obviously, we're very excited about the ability to put multiple things in. We are going to add a couple of more components, and we'll be talking about those things later this year at conferences in the second half of the year, but expect some added bells and whistles to the CARB-B7H3 program beyond what we have today to add further attributes for the purpose of going to solid tumor settings. Okay, thank you very much.

Sure thing Scott and obviously, we're very excited about the ability to put multiple things and.

We are going to add a couple of more components and we'll be talking about those things later this year at this conference and the second half of the year, but expect some added bells and whistles to car piece of and Asia III program and beyond what we have today to add further attribution for the purpose of going to solid tumor settings.

Okay. Thank you very much.

Scott Walshko: I would say, generally, though, for where we're starting in solid tumors, building off of the FT538 backbone, which already has three edits and includes the CDT.

I would say generally, though for where we're starting and solid tumors.

And is building off of the Ft, 538, backbone, which already has three edits and includes the CD 16 receptor.

Your next question comes from the line of Mara Goldstein from Mizuho. Your line is now open.

Mara Goldstein: Your next question comes from the line of Mara Goldstein from Missoula. Your line is now open.

Scott Walshko: Great, thanks so much for taking the question. Just, you know, a question on the DCMA program in multiple myeloma. And I'm just wondering how you view what will ultimately be the true competitive landscape for the programs on the NK side that you're working on relative to what we see currently in the clinical marketplace today. Bye!

Great. Thanks, so much for taking the question.

A question on that that'd be hem a program.

And multiple myeloma and I'm, just wondering how you view and what will ultimately be the true competitive landscape.

For the program to on the E&P side that you'll work non relative to.

What we see currently and you know.

Clinical marketplace today.

I think theres going to continue to be a significant amount of innovation in the myeloma space and obviously, we are partnered with Janssen, who is a company that has.

Scott Walshko: I think there's going to continue to be a significant amount of innovation in the myeloma space, and obviously, we are partnered with Janssen, who is a company that has, you know, arguably the leading franchise in myeloma and has, probably, at least today, a best-in-class CARB-BCMA product candidate that is patient-derived. So I do think the landscape in myelo I think it's going to lend itself to the duration of treatments.

Arguably the leading franchise in myeloma.

And has a probably at least today a best in class car be CMA product candidate.

<unk>.

That is patient derived so I do think I do think the landscape and myeloma given the very nature of that disease is going to lend itself to off the shelf treatment I think it's going to lend itself to duration of therapies and I do think it will lend itself today given there are relapsed.

Scott Walshko: And I do think it will lend itself today, given there are relapse rates that are still meaningful and significant, to a multi-pronged approach to the disease, including embedding multiple mechanisms of action within the cell therapy. I mean, if you look at today's myeloma, right, it's littered with combination therapies, right, which bring multiple mechanisms of action to attack the plasma cells. I think long term, as you think about how you attack myeloma and potentially try and cure it, it's going to take multiple mechanisms of action, and so that's one of the things we're super excited about with the cell therapy approach, especially IPS-derived. You can embed those multiple mechanisms of action within a single modality, cell therapy.

Rates that are still meaningful and significant.

Two a multipronged approach to the disease.

Including embedding multiple mechanisms of action within the cell therapy, I mean, if you look at today right and myeloma right. It's littered with combination therapy is right, which bring multiple mechanisms actions to attack the plasma cells I think long term as you think about how do you attack myeloma and potentially try and cure it it's going to take multiple mechanisms of action and so that's one of the things worse.

We're excited about its cell therapy with a cell therapy approach, especially Ips derived you can embed those multiple mechanisms of action within a single modality the cell therapy.

Scott Walshko: And I'd like to just ask what you're thinking for this year in terms of your approach to the release of data. You know, last year, when we left last year, you had said that you would wait until you had, you know, sort of critical mass and cohorts. So how are you guys thinking about it this year?

Okay, and I can just ask one.

What youre thinking for for this year in terms of your approach to release that data.

Staring hitting last year and you had said that you would wait until you had sort of critical mass and cohort. So how are you guys thinking about it this year.

Sure I'll, let him.

Edward J. Dulac: Sure, I'll let Ed...

Edward J. Dulac: Yeah.

Tackled it yes.

Edward J. Dulac: Thank you.

Yes, hi.

Edward J. Dulac: We're trying to consolidate things into a more manageable, digestible format for disease areas. And so, similar to what we did at ASH this year around CD16 biology, I think you'll see us take a disease-oriented approach. And I think there are four major milestones to look forward to in 2021. The first one is likely to be around AML, where as we get into late spring or early summer, we have both FT516 and FT538 now dosing patients in AML.

We're trying to consolidate things into a more manageable and digestible format of disease areas and so similar to what we did at Ash. This year round CD 16, biology, I think you'll see us to a disease oriented approach and I think there's four major milestones to look forward to in 2021. The first one is likely to be around AML, where as we get into late spring early.

Early summer, we have both ft, 516, and Ft, 538, now dosing patients and AML. So we'll have some updates from those programs call. It by middle of the year. Shortly thereafter, we'll probably revisit lymphoma, where we have both ft 516, and combination with rituximab as well as the ongoing monotherapy and combination with Rituximab per FTE.

Edward J. Dulac: So, we'll have some updates from those programs, call it by the middle of the year. Shortly thereafter, we'll probably revisit lymphoma, where we have both FT516 in combination with rituximab, as well as the ongoing monotherapy in combination with rituximab for FT596. The third major milestone will probably come in the third quarter, and it'll be emphasizing solid tumors, where we have FT500 ongoing in an expansion, and we're making good progress there, as well as what Scott mentioned in his prepared remarks around FT516 in combination with Velumab.

596.

The third major milestone will probably come in the third quarter and it'll be emphasizing solid tumors, where we have ft, 500, ongoing and and expansion and we're making good progress there as well as what Scott mentioned in his prepared remarks around ft, 516, and combination with our value Mab. We also may have an opportunity to talk about the IND filings that we also rep.

Edward J. Dulac: We also may have an opportunity to talk about the IND filings that we also referenced around FT536, our CAR-MIC-A and MIC-B programs, as well as the progress we're making with Janssen on, again, an antigen that's not been disclosed, but we'll plan to file an IND. So we have quite a bit going on clinically, but also pre-clinically in terms of new innovation around solid And then lastly and fourthly, around ASH, we'd like to have a good presence in multiple myeloma with FT538 in combination with daratumumab, and then a small but, you know, hopefully good number of patients with FT576, for which we cleared the IND at the end of last year, and we'll begin treating those patients as we get into the second half of this year.

Ernst around Ft, 536, our car Mckay Mcbee program as well as the progress, we're making with Janssen on again and Amgen and it's not been disclosed, but we will plan to file an IND. So we have quite a bit going on and clinically but also pre clinically in terms of new innovation around solid tumors that we will talk about in the third quarter and then lastly enforced.

And around ash and we'd like to have a good presence and multiple myeloma with ft, $5 38, and combination with Terra tumor Mab and then a small but you know hopefully good number of patients and ft, $5 76 for which we cleared the IND at the end of last year and will begin to those patients as they get into the second half of this year, so quite a bit going on clinically focused on disease areas.

Edward J. Dulac: So quite a bit going on clinically, focused on disease areas, and, you know, as we get into the fourth quarter with ASH specifically, we could use it as an opportunity to revisit lymphoma or additional data as well. Lots of clinical data set for 2021, around four key times of the year beginning, you know, mid-year.

And as we get into the fourth quarter with Ash, specifically, we could use it as an opportunity to revisit lymphoma or additional data as well so lots of clinical data set for 2021 around four key times of the year, beginning mid mid year, with AML, and yeah, and as well as AML at ash potentially too right.

Okay I really appreciate it thanks.

Sure.

Next question is from month day Blair from Oppenheimer. Your line is now open.

Hey, guys How's it going on.

No.

Maybe I missed it but if you could just maybe walk me through 596 as planned protocol amendment in terms of dosing is it going to be the same dose you have now and divide it out overall over several infusions. So I know youre on 90 million now would it be like.

Scott Walshko: Yeah, and as well as I am.

Scott Walshko: As well as AML.

Scott Walshko: [inaudible]

Scott Walshko: Okay, I really appreciate it, thanks. Sure. Next question is from Mark Biegler from Oppenheimer. Your line is now open. Hey, guys, how's it going? Locked on. Good. So, um, www.yigalnochomovitz.com

Let's say $30 million over three doses and Larry I guess, what Youre doing with 516 and five greater interest any color you can give there might be helpful. And I think I think our plan would be to the dose level. We're currently cleared on and we would begin multi dosing that cleared dose.

Operator: ...

Operator: [inaudible]

Scott Walshko: We would begin multi-dosing that clear dose.

Scott Walshko: So if we're cleared, for instance, let's just pick 90 million cells. Let's say we're cleared 90 million cells as a single dose. We may have a protocol where it's three doses of 90 million cells each.

Okay, Okay, and so if we're cleared for instance, let's just pick 90 million cells lets say were cleared 90 million cells as a single dose. We may have a protocol, where its three doses of 90 million cells each.

Scott Walshko: Oh, okay. That's great. Cool.

Oh, Okay interesting.

That's great color.

Scott Walshko: If you go back, if you go back, I mean, the analogy is if you look at the 819 protocol that we have, where the 819 protocol has single dose and multi-dosing as well as the 576 protocol that has single dose and multi-dosing, you essentially clear a single dose level of say, pick it 100 million cells. Once you clear that single dose level of 100 million cells, you can begin multi-dosing with that cleared dose level. So you could do two 100 million cell doses.

I mean, if you go back and if you'd go back I mean, the analogy is if you look at the 819 protocol that we have where the 819 protocol has single dose and multi dosing as well as the $5 seven and six protocol that has single dose and multi dosing you essentially clear a single dose level of say Pickett and 100 million cells. Once you clear.

That single dose level of 100 million cells, you can begin multi dosing with that cleared dose level. So you could do to 100 million cell doses.

Got it and makes sense.

And then I had just maybe more of a subjective question, but have.

Have you noticed any uptick in patient recruitment or investigator interest and your trials falling the ash data set I mean, obviously a lot of the indications are going after a pretty competitive and in terms of investigational therapies. So just any.

Scott Walshko: Got it. That makes sense.

Scott Walshko: Have you noticed any uptick in patient recruitment or investigator interest in your trials following the ASH data set?

And any type of suggests objective insight you have would be helpful.

Scott Walshko: Yeah, I definitely think, I mean, we've seen a lot of interest, and there has historically, you know, been a lot of interest in our IPS-derived cell therapy programs. But, part of the challenge that we deal with today is, you know, we are in dose escalation, so we're gated, right, by how fast we can potentially move. So, you know, today we're focused on a core number of sites that we think can help us manage through dose escalation in an efficient way. But obviously, once we get to dose expansion, you know, for instance, like with FT-516, we have the potential to open that up much more broadly, and yes, we think there's significant interest. Thanks, guys. Sure.

Yeah, I definitely think I mean, we've seen a lot of interest and there has historically been a lot of interest and our Ips derived.

Cell therapy programs.

Part of the challenge that we deal with today is we are in dose escalation. So we're gated by how fast we can potentially move. So today, we're focused on a core number of sites that we think can help us manage through dose escalation and efficient way, but obviously once we get to dose expansion play for instance, like with Ft 516, we.

Have the potential to open up that to open that up much more broadly and yes, we think there's significant interest there.

Well thanks, guys.

Sure.

Next question is from that Ben Burnett from Stifel. Your line is now open.

Carolina Ibanez: The next question is from Ben Burnett from Spice Hill. Your line is now open. Hi, good afternoon. This is Carolina Ibanez-Mentoson on behalf of Ben Burnett.

Hi, Good afternoon. This is Catalina island and peso.

And I'm sort of bandwidth net thank you from taking our questions.

Scott Walshko: Thank you for taking our questions. I was wondering, can you provide any color on the type of high-risk patients being enrolled in the University of Minnesota's RELAP prevention study? And when might we get a look at clinical data there?

And I was wondering can you provide.

Any color on the type of high risk patients being enrolled into the University of Minnesota is relapse prevention study and.

And when might we get a little guidance.

Clinical data and they are.

Wayne Hsu: Sure, Wayne, do you want to take that? I mean, with respect to clinical data, I'll jump on that. You know, obviously, it's an investigator-initiated study, so we'll work with the University of Minnesota with respect to clinical data. I would not expect clinical data on that program before ASH, though, given that the study is a relapse prevention study.

Sure and Wayne do you want it and you want to take that I mean with respect to clinical data and I'll jump on that.

Obviously, it's an investigator initiated study so we will work with the University of Minnesota with respect to clinical data.

And would not expect clinical data before ash, though on that program at the at the earliest given that the study is a relapse prevention study.

Scott Walshko: But go ahead, Wayne.

But go ahead Wayne.

With respect to the study design and the way the way. It goes is that patients with high risk.

Wayne Hsu: Yeah, and with respect to the study design, the way it goes is that patients with high-risk B-cell lymphoma, and these are patients, you know, that have relapsed or there are refractories from their initial therapy. And then these are patients who, otherwise, would undergo high-dose chemotherapy followed by an autologous stem cell transplant. And so the design of the study is essentially to take that high-dose chemotherapy followed by autologous stem cell transplant and then add the combination of FT-596 plus rituximab following transplantation.

T cell lymphoma, and these are patients that have relapsed or refractory from there from their initial therapy and then these are patients who otherwise would undergo high dose chemotherapy, followed by autologous stem cell transplant and so the design of the studies essentially to take that high dose.

Chemotherapy, followed by autologous stem cell transplant, and then add the combination of Ft, 596, plus rituximab following transplant and so that's where the relapse prevention and comes from because we know historically that patients who undergo autologous stem cell transplant at least half.

Wayne Hsu: And so that's where the relapse prevention comes from because we know historically that patients who undergo autologous stem cell transplantation, at least half of them will still have relapsed disease following transplant. And so one of the primary endpoints for the study is essentially relapse-free survival to see whether or not we can increase the percentage of patients who are relapse-free following autologous transplantation.

And then well well still.

Relapsed disease following transplant and so one of the primary endpoints for the study is.

It was essentially a relapse free survival to see whether or not we can increase the percentage of patients who are relapsed free.

Following autologous transplant.

Okay got it and Tim.

Operator: Okay, got it. And we haven't seen much evidence of CRS or neurotoxicity with current K cells in lymphoma. Do you expect a similar result with current K?

And we haven't seen much evidence of CRA and so on unit toxicity with cutting K sales have been from that.

And just take cost senior debt yourselves with current Kay and the multiple myeloma setting.

This is pure.

Your speculation go ahead and go ahead Wayne.

Operator: All right.

Wayne Hsu: It's pure speculation, of course, you know, but I think that we have been encouraged by what we have seen with other NK cell product candidates, particularly those in lymphoma, where, in contrast to CAR T therapies that are targeting the same antigen in CD19, we certainly don't see the frequency nor the severity of cytokine release syndrome that have been observed with CAR T. And as Scott mentioned, you know, in our FT So, for what it's worth, we're encouraged by that, and we hope to see the same pattern in our myeloma. Okay, great.

It's pure speculation of course, but I think that we have been encouraged by what we have seen with other NK cell product candidates, particularly those in lymphoma.

And in contrast.

Two car T therapies that are targeting the same antigen and CD 19, we certainly don't see the frequency nor the severity of cytokine release syndrome, or neuro Tox debt had been observed with car T and as Scott mentioned.

And.

And our Ft, 516, and Ft 596 data to date, we haven't seen any grade Crs or neurotoxicity. So.

For what it's worth we're encouraged by that.

That and we hope that we hope to see the same pattern and.

Myeloma programs.

Wayne Hsu: Okay, great. Much appreciated. The next question is from Doreen Amin from Jeffries. Your line is now open.

Okay, great much appreciate it.

Yeah.

Next question is from there and Amen from Jefferies. Your line is now open.

Doreen Amin: Yeah, hi guys. Thanks for taking my questions.

Yeah, Hi, guys. Thanks for taking my questions, maybe on 538 with a combination with terra and multiple myeloma.

Scott Walshko: Maybe on 538, in combination with Dara and multiple myeloma, I think you stated that first dose at 100 million cells in patients who have failed at least two lines of therapy. Can you just talk about, I guess, prior lines of therapy? Because typically, I guess in, you know, with the BCMA card... we're seeing a median of about five or six lines of therapy. Are you expecting patients at third line in that trial, or would you expect, you know, more refractory patients, and this is just simply the inclusion criteria?

Thank you stated that first dose.

The 100 million cells and patients who have failed at least two lines of therapy can you just talk about I guess prior lines of therapy, because typically I guess in you know with the PCM, Inc. We're seeing a median of about five or six lines of therapy are you expecting patients and third line and that trial or would you expect more of a free.

Free patients and this is just simply like the inclusion criteria.

Wayne Hsu: Sure. Go ahead, Wayne.

Sure go ahead go ahead Wayne.

Yes, so I mean.

Wayne Hsu: Yeah, so... I mean, it's a fair question, right?

It's a fair question right from an eligibility standpoint, we say that patients have to have received two prior lines of therapy and that and that's true.

Wayne Hsu: From an eligibility standpoint, we say that patients have to have received two prior lines of therapy, and that's just with respect to standard myeloma agents, such as a proteasome inhibitor, IMID, so on and so forth. But I think realistically, as we begin to enroll patients in this trial, at least initially, we would expect to see patients who have received more than just two prior lines of therapy, and we'll probably be seeing a patient population akin to what has been enrolled with respect to the BCMA-directed CAR-T therapy.

With respect to.

Standard myeloma agents, such as a proteasome inhibitor and they did so and so forth.

And but I think realistically as we begin to enroll patients on this trial.

Initially we would expect to see patients who received more than just two prior lines of therapy, and we'll probably be seeing a patient population akin to what has been enrolled with respect to the <unk> directed car T therapies.

Wayne Hsu: Okay, that's helpful. And then you mentioned a focus on the T-cells earlier, Scott. Can you maybe just give us a status update on FT819? I think the IND cleared last July on clintrials.gov, and the design was up in November.

Okay. That's helpful and then.

You mentioned a focus on the T cells earlier, Scott can you, maybe just give us a status update on FTE, a one nine and I think the I and declared last July.

<unk> trials Dot Gov. The design was up in November.

Scott Walshko: I guess, you know, what are the steps you need in order to achieve patient dosing? And then a question on that is there was a paper, I think, last month from Takeda Researchers, I think the lead author is Eri Gucci, talking about, you know, just iPSC cell differentiation for T-cells and talked about, I guess, challenges with CD4s in particular versus CD8. I'm not sure if you saw that paper, but could you maybe comment on your efforts and what you've seen with differentiation on CD4s versus CD8s?

I guess you know what are the steps you need in order to achieve patient dosing and then.

A question off of that is there was a paper I think last month from Takeda researchers I think lead authors and Gucci talking about.

And just IP SC cell differentiation for T cells, and talked about I guess challenges with CD force and particular versus <unk>.

Not sure if you saw that pay for it but if you could maybe comment on your efforts.

And what you've seen and.

And with differentiation on CD force for subsidy eights.

Bahram Valamehr: Sure, Bob's nodding his head, so I'll let Bob answer the second question. The first question is, have we completed the first manufacturing run for 819? We're currently doing product release testing on that batch that we manufactured. Obviously, getting to the point you're making and Bob will discuss, we think there's obviously continued opportunity for process improvements with respect to developing really high-quality alpha beta T-cells. And we're working on some of those improvements in parallel in real time, including through our collaborations with Ono and Janssen.

Sure Bob Bob is nodding his head so I'll, let Bob answer the second question and the first question is could we completed the first manufacturing run for 2019. We're currently doing product release testing on that batch that we manufactured obviously getting to.

The point, you're making and Bob will discuss we think there is obviously continued opportunity for process improvements with respect to developing out really high quality Alpha beta T cells and we're working on some of those improvements in.

In parallel in real time, including under our collaboration with Ono and Janssen and we are and we have kicked off a second manufacturing run where we've implemented those improvements and so we're continuing to do a little bit of work assessing the improvements and we've guided that we will enroll the first patient in the middle of this year.

Bahram Valamehr: And we have kicked off a second manufacturing run where we've implemented those improvements. And so we're continuing to do a little bit of work assessing the improvements, and we expect to enroll the first patient in the middle of this year.

And I'll follow up Scott.

Bahram Valamehr: I'll follow Scott's point, obviously referring to the Nature Communications Study where they took T-cells and they reprogrammed them, so there was no TCR engineering, and they had the, even though they had challenges, they actually took a shortcut because they had the opportunity to just have the endogenous TCR that they could take advantage of. What we've done over the past four or five years with Michelle Satterlein has been basically coming up with a strategy where you don't have the TCR available because we're going into an allogeneic setting and how to mitigate TCR signaling with a car.

Obviously, you're referring to and nature Communications study.

They took.

T cells and day reprogram. So there was no a TCR engineering and they had the even though they had challenges they actually took a shortcut because they had the opportunity to just have the endogenous TCR that they can take advantage of what we've done over the past four or five years with Michelle satellite and that's been.

Basically coming out with a strategy, where you don't have to TCR available, because we're going into and allogeneic setting and how to mitigate TCR signaling with a car and that's why we put the car and to track locus, It turns out and try and hematopoiesis and and a temporary manner. It gives us the signal we need for T cell selection. So it was a very complicated process.

Bahram Valamehr: And that's where we put the car in the track locus, it turns on during hematopoiesis, and in a temporal manner, it gives us the signal we need for T cell selection. So it's a very complicated process.

Yeah.

Bahram Valamehr: To answer your question about CD8s and CD4s, the composition of our FT819 is a CD8 product. It is a very highly effective effector cell population. The CD4 compartment has always been discussed as a helper population, and that population you need for long-term persistence when you have a single dose.

To your question about our city Ace and C. D force the composition of our eight Ftes and one nine as a CD eight product. It is and it's a very highly effective effector cell population.

The CD four compartment and that's always been discussed as a help her population and that population you need for the long term persistence and when you have a single dose so here and a multi dose manner, we feel that the CD eight are the proper.

Bahram Valamehr: So here, in a multi-dose manner, we feel that the CD8s are the proper dosing strategy for our first product. We are actively working on making CD4s on the side, but CD8s are the focus of FT819. So basically, that's our strategy, make CD8s carry in the car and make CD4s on a different timeline.

Dosing strategy for our first product we are actively working on making C. D force on the side, but city ASR the focus of F. T. Eight one night.

So basically that's our strategy makes 80 eights.

And the car and make Citi Force.

And in a different timeline.

Bahram Valamehr: Great. Thanks. That's helpful. Sure.

Great. Thanks, that's helpful.

Sure.

Operator: [inaudible] Your next question comes from the line of Peter Lawson from Barclays. Your line is now open. Hey, Scott.

Your next.

Next question comes from the line of Peter Lawson from Barclays. Your line is now open.

Hey, Scott Thanks for taking the questions.

Peter Richard Lawson: Thanks for taking the questions. The AML data that we get kind of mid-year-ish, is that going to be kind of... ASCO, or is it kind of like a press release? What's the plan around it? Yeah, now, I mean we'll continue to do what we've done in the past. I mean whether or not it will be

The AML data that we get kind of mid year ish is that going to be kind of.

<unk> or is it kind of like a press release, what's the what's the plan around.

And we'll continue that what we've done and in the past I mean, whether it will be part of a conference agenda or we will do it alongside the conference like we did at Ft 516 at Ash.

Scott Walshko: Part of a conference agenda, or we will do it alongside the conference, like we did FT 516 at Ashe. We'll do it as part of a scientific conference. We're not just going to do it as part of just a one-off press release. You know, we'll do it, and we'll announce it as part of some type of Thank you.

We will do it as part of a scientific conference we're not just going to do it as part of just a one off press release will.

And we'll announce that as part of some type of event.

And what is the best.

Scott Walshko: What's the best bar there for 516 and 538 in AML, is it? You kind of want to be on par with the aloe kind of approaches for NK cells, or... I think you want, yeah, I mean...

Therefore, $5 and sits and 538 and AML is it.

And you kind of want to be on par with the.

Allo and kind of approaches for NK So I.

Yeah I mean.

No and historically I think you look I think people have been and.

Scott Walshko: I mean, historically, I think people have been honestly excited about some of the complete responses that have been generated in AML, and again, relapsed refractory AML, these are patients that really don't have any great options, and they're not in a position, given the state of their disease, where they can go on to transplant. And so, you know, we're certainly looking at, and we talked about the limitations of donor-derived NK cell therapy, that it wasn't really scalable, given some of the limitations.

Honestly excited about some of the complete responses that have been generated in AML and again relapsed refractory AML and these are patients that really don't have any great options and theyre not in a position given the state of their disease, where they can go on to transplant and so we're certainly looking at and and we've talked about the limitations with Doe.

<unk> derived NK cell therapy that it wasn't really scalable given some of the limitations and so if we can come in with and off the shelf cell therapy.

Scott Walshko: And so, you know, if we can come in with an off-the-shelf cell therapy, you know, achieve, you know, CR, CRI rates of 20 to 30 percent, drive patients to leukemic-free state, where they can bridge to transplant with an off-the-shelf product candidate, I think that's a great option, and I think there's a meaningful therapeutic impact that you can have for patients with relapsed refractory AML, if we can achieve that.

Achieved CR cri rates of 20% to 30% drive patients to leukemic.

Free state, where they can bridge to transplant with and off the shelf product candidate I think that I think that's a great option.

And I think there's a meaningful therapeutic impact that you can have for patients with relapsed refractory AML, if we can achieve that.

Scott Walshko: I do say I will stand by.

And I do say I will just I will standby the comment I made earlier that long term if you start thinking about long term and AML.

Scott Walshko: The comment I made earlier, though, long-term, if you start thinking about long-term AML, yeah, you will have engineered targeted strategies. Okay.

Yes.

You will have engineered targeted strategies.

Okay and.

Scott Walshko: And then just generally, as we kind of think about repeat dosing, do you think on repeat dosing there's going to be an increase in the chance of graft rejection, essentially?

And then just generally as we kind of think about repeat dosing and do you think only repeat dosing is going to be and increased <unk>.

So of graft rejection essentially.

Scott Walshko: It's an interesting question. I mean, we look at this for every single patient that we treat across any of our programs, 500, 516, 596, 538. I mean, we look for this. And we have not seen T or B cell mediated rejection arise.

And it's an interesting question.

We look at this for every single patient that we treat across any of our programs $505 16, five nine and 65 38 I mean, we look for this we have not seen tier b cell mediated rejection arise.

Scott Walshko: Now, it's a fair question. As you go out further on the curve and further out from conditioning, as you do more rounds of conditioning, will that arise? It's a fair question, and it's something Wayne alluded to.

It's a fair question as you go out further on the curve and further out from conditioning as you do more rounds of conditioning will that arise. It's a fair question and its something as sort of Wayne alluded to we're interested and in investigating including comparing it to non <unk>.

Scott Walshko: We're interested in investigating it, including comparing it to non-psi flu conditioning regimens.

Sigh flu conditioning regimens.

Scott Walshko: That's kind of my next question. Do you think we can get away from side conditioning?

Kind of my next question.

Do you think we can get away from.

Flu side conditioning.

Scott Walshko: I think we're going to begin investigating that in pretty short order.

Yeah.

I think we're going to begin investigating that in pretty short order.

Scott Walshko: Okay. Thank you so much.

Okay.

Thank you so much thanks.

Nick Abbott: Sure. Your next question comes from the line of Nick Abbott from Wells Fargo. Your line is now open.

Thanks for taking the question.

Your next question comes from the line of and Nick <unk> from Wells Fargo. Your line is now open.

Scott Walshko: Good afternoon, and thanks for taking my questions. So, Scott, you've probably treated over 40 patients now in the FT500 series of trials. Can you talk a little bit about the clinical protocol logistics? I mean, there's no obvious need for bridging therapy, presumably, but that, you know, would rely on the fact that everything goes well and the cells are there, and, you know, the patients get their fluci on time. And then, have any patients required hospitalization before or immediately after for treatment-related AE? I know the cells are given in the outpatient setting, but I'm just wondering about rates of hospitalization, and I have a follow-up. Yeah, I think so.

Good afternoon, and thanks for taking my questions.

And you probably treated over 40 patients now and Ft 500 series of trials can you talk a little bit about the clinical protocol logistics I mean that there's no obvious need for bridging therapy.

<unk>.

Pino would rely on the fact that everything goes well and the sales are there and you know the patients get the susana and on time.

And then how does any patients required hospitalization before or immediately after for treatment related AE I know the sales are given and the outpatient setting, but I'm just wondering about rates and hospitalization.

And I have a follow up yeah, I think I mean, I went and can talk about sort of what we've seen in preparing patients I mean, we've seen.

Wayne Hsu: Wayne can talk about the sort of what we've seen in preparing patients. I mean, we've seen, you know, very little utilization of or need to use a sort of bridging strategy, given that the cells are there, they can be administered off the shelf. We've obviously never discussed hospitalization rates, but most of our product candidates are designed per the protocol to be delivered in the outpatient setting. I will say, though, there are certain centers when they treat the first patient, for example, or the first second patient at that center, where they do initially require hospitalization for a short period of time, just because it's the first time with respect to the therapy.

Very little is utilization or need to use a sort of a bridging strategy given the given the third the cells are there they can be administered off the shelf.

We've obviously never discussed hospitalization rates, but most of our product candidates are designed per the protocol to be delivered and the outpatient setting I will say, though there are certain centers when they treat the first patient for example are the first second patient at that center, where they do initially require <unk>.

Hospitalization for a short period of time, just because it's the first time of with respect to the therapy.

Wayne Hsu: Yeah, I mean, just to add to that, you know, in our cumulative experience to date, we have virtually no instances where a patient received, you know, quote, bridging therapy where the reason for administering that bridging therapy was to buy time until the FT series of cells were made available. So it was really, you know, in most cases, as exemplified by what we discussed earlier, patients who are refractory to their last therapy, as soon as they become eligible for the study, they come on to the study, they get their flu vaccine, and they get their cells; they do not have to have, you know, single agent chemotherapy as a tie-over.

Yeah.

Yes, I mean, I think just to add to that.

And our cumulative experience to date.

We have.

Virtually no instances, where a patient received.

Bridging therapy.

Where are the reason for administering that bridging therapy was to buy time until FTE series of sales were made available. So it was really.

And in most cases thats exemplified by what we discussed earlier.

Patients who are refractory from their last therapy as soon as they become eligible for the study they come onto the study they get there from sky and they get themselves they've not had to have.

Single agent chemotherapy as a tie over so that is almost virtually non existent and our experience to date.

Wayne Hsu: So that that is almost virtually non existent in our experience to date. And then as far as hospitalizations are concerned, I think one thing that's worth, you know, reminding people is that, you know, to date, we have not seen any serious adverse events that are attributable to any of the cell products, which means that in virtually all cases, patients who require hospitalization during the treatment period are hospitalized for things other than

And then as far as hospitalizations concern I think one thing that's worth.

Reminding us that to date, we have not seen any serious adverse events that are attributable to any of the cell products, which means that and more.

And virtually all cases patients who require hospitalization during the treatment period. They are hospitalized for things other than effects of itself and it.

Wayne Hsu: And it's most often due to the patient's underlying disease, as well as, in some cases, effects from the flu side effects, which are expected given what we know about the safety profile for that combination.

Most most often due to the patient's underlying disease.

As well as.

And in some cases.

Effects from the food side conditioning, which are expected given what we know about the safety profile for for that combination.

Scott Walshko: That's helpful. And for the expansion cohorts, you know, it sounds like at least in some of them you're going to do some additional exploration of those, and as you've mentioned, lymphoconditioning. Are you going to begin to focus on specific cohorts? And I'm thinking of AML, where you could have, you know, a cohort of primary induction failures, early relapse, or even, you know, elderly frontline patients who are ineligible for intensive induction therapy.

Okay, that's helpful and.

And I think expansion cohorts.

It sounds like at least in and some of them you're going to do some additional exploration of debt.

Yes, and as you mentioned.

And then for conditioning.

Going to begin to focus on specific cohorts and I'm thinking of AML, where you could have.

A cohort of primary induction failure, a degree that sleeve and elderly frontline patients who are ineligible for intensive induction therapy.

Scott Walshko: Yeah, absolutely. I think that is absolutely an opportunity in AML, certainly given the different lines of therapy. I think where we will absolutely start to see this is with FT516 and lymphoma, where today we have, you know, the most flexibility given we're at the highest dose level and give it the safety and efficacy profile we've seen to date.

Yeah, absolutely I think.

And that is absolutely an opportunity in AML certainly given the different lines of therapy, I think where we will absolutely start to it and you'll start to see this as with ft 516 and lymphoma.

Where today, we have the most flexibility given we're at the highest dose level and give it the safety and efficacy profile, we've seen to date.

Scott Walshko: Okay, thanks. And just last one, you mentioned that there are some improvements for 819. Are you going to complete this second batch before you decide which to use?

Okay. Thanks, and then.

And just last one you mentioned that there are some improvements for 819.

And you're going to complete this second.

And equally you decide which to us.

Scott Walshko: We probably will. I mean, we've done a lot of work on the first batch, and we're actually very comfortable with the in vivo efficacy we're seeing from the first batch. But like I said, we're always innovating. We have implemented some process improvements on the preclinical side, and in preclinical studies, they do make a difference. So we are going to take a look at the second batch.

And the middle and we'd probably yeah, we probably will I mean, we've done a lot of work on the first batch and.

We're actually very comfortable with the in vivo efficacy were seeing from the first batch, but like I said, we're always innovating we have implemented some process improvements on the preclinical side and pre clinically they they do make a difference.

So we are going to take we are going to take a look at the second batch.

Scott Walshko: Okay, and then do it by... By extrapolation, then, should we assume that you've not felt the need to do that with the NK portfolio?

Okay and then.

My Extrapolation and then should we assume the not felt the need to do that with the.

And cable earlier.

Scott Walshko: With the NK portfolio, we have definitely made process improvements over time, but this was a situation where we were making a process improvement in real time before we had treated the first patient. There was an element of innovation that occurred prior to treating the first patient.

With the NK portfolio, we have definitely made process improvements overtime.

But this was a situation where we're making a process improvement in real time before we had treated the first patient.

Okay, great. Thank you right now there is an element there was an element of innovation that occurred.

Prior to treating the first patient.

Scott Walshko: Thanks, y'all.

Okay.

Operator: Yep. So, all right. That is your last question, Chris Sanchez. You may continue.

Thanks Scott.

And here.

So.

Right.

That is your last question for Sanjay as you May continue.

Chris Sanchez: Perfect. Thank you everyone for participating in today's call. Best wishes.

Perfect. Thank you everyone for participating in today's call best wishes.

Operator: Thank you all for your participation in today's call and your continued interest and support of Fate Therapeutics. Be well. You may now all disconnect.

Thank you all for your participation and today's call I heard something of interest and support of <unk>.

P. IDEXX. Meanwhile, you may now all disconnect.

Okay.

And then.

And then.

[music].

And.

Non-GAAP.

Moving forward.

And then.

And then.

[music].