Q2 2020 Fate Therapeutics Inc Earnings Call

At this time, all participants only listen only mode.

Operator: At this time, all participants are in a listen-only mode. This call has been webcast live on the Investor & Media section of Fate's website at FateTherapeutics.com. As a reminder, today's call is being recorded. I would now like to introduce Scott Washko, President and CEO of Fate Therapeutics. You may begin.

This call is being webcast lab, they investor and media section of fates website at face it fate therapeutics Dot com.

As a reminder, today's call is being recorded.

I would now like to introduce Scott Watsco, President and CEO, Oh, Oh fate Therapeutics you may begin.

Scott Washko: Thank you. Good afternoon, and thanks, everyone, for joining us for the Fate Therapeutics second 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 & Media section of our website under Press Release. In addition, our Form 10-Q for the quarter ended June 30, 2020, was filed shortly thereafter, and can be found on the Investors & Media section of our website under Financial Information. Before we begin, I'd like to remind everyone that, except for statements of historical facts, the statements made by management and responses to questions on this conference call are forward-looking statements under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements.

Thank you.

Good afternoon, and thanks, everyone for joining us for the fate Therapeutics second quarter 2020 financial results call.

Shortly after four PM Eastern time today, we issued a press release with these results, which can be found on the investors immediate section of our web site under press releases. In addition, our form 10-Q for the quarter ended June 30, 2020 was filed shortly thereafter and can be found on the investors immediate section of our website under.

Financial information.

Before we begin I'd like to remind everyone that except for statements of historical facts. The statements made by management and responses to questions. On this conference call are forward looking statements under the Safe Harbor provisions of the private Securities Litigation Reform Act of 1995.

These statements involve risks and uncertainties that can cause actual results could differ materially from those in such forward looking statements.

Scott Washko: Please see the forward-looking statement disclaimer in 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-Q for the quarter ended June 30, 2020, that was filed with the SEC today. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, as the facts and circumstances underlying these forward-looking statements may change. Except as required by law, Fate Therapeutics disclaims any obligation to update these forward-looking statements to reflect future information, events, or circumstances. Joining me on today's call are Dr. Dan Shoemaker, our Chief Scientific Officer; Dr. Bob Valamehr, our Chief Development Officer; and Dr. Wayne Chu, our Senior Vice President of Clinical Development.

We see the forward looking statement disclaimer on the Companys earnings press release issued after the close of market today as well as the risk factors and the company's FCC filings, including in our form 10-Q for the quarter ended June 30, 2020 that was filed with the FCC today.

Undue reliance should not be placed on forward looking statements, which speak only as of the date. There me as the facts and circumstances underlying these forward looking statements may change.

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

Joining me on today's call are Dr., Dan Shoemaker, our Chief Scientific officer.

Dr., Bob Bellemare, our Chief Development Officer, and Dr. Wayne Chu, our senior Vice President of clinical development.

Today, I will provide an update on our business operations as we continue to navigate through the cobot 19 pandemic and highlight certain key accomplishments, we achieved over the past several months that underscore the unparalleled advantages afforded by our proprietary I P. S C product platform and our unique.

Scott Washko: Today, I will provide an update on our business operations as we continue to navigate through the COVID-19 pandemic and highlight certain key accomplishments we achieved over the past several months that underscore the unparalleled advantages afforded by our proprietary IPSC product platform and our unique ability to bring multiplexed, engineered cell-based cancer immunotherapies in response to the COVID-19 pandemic. Over the last several months, we have implemented and expanded numerous measures to protect the health and safety of our employees, their families, and the extended community while continuing to operate our business. Through the commitment, resilience, and compliance of our employees, we continue to maintain strong execution and a rapid pace of innovation.

Ability to bring multiplexed engineered cell based cancer immunotherapies to patients.

In response to the Cobot 19 pandemic over the last several months, we have implemented an expanded numerous measures to protect the health and safety of our employees their families and the extended community while continuing to operate our business.

Through the commitment resilience and compliance of our employees, we continue to maintain strong execution and a rapid pace of innovation.

Scott Washko: And we have achieved several important milestones, including treating the first patients with FT596, an off-the-shelf, multi-antigen targeted, CAR-19 and K-cell product candidate for B-cell malignancy. Clearing our IND applications with the FDA for FT538, the first-ever CRISPR-edited IPS-derived cell therapy, as well as for FT819, the first ever IPS-derived CAR T-cell therapy, and forming and launching a transformative partnership with Janssen, bringing together our industry-leading IPSC product platform with Janssen's proprietary tumor-targeting antigen binders to develop novel off We have also continued to leverage the significant advantages that come with controlling our own in-house GMP manufacturing operations, as we produced hundreds of cryo-preserved, infusion-ready doses of our product cannabis, which are now stored in inventory and are available off the shelf for use in our clinical studies.

And we have achieved several important milestones, including treating the first patients with up to 596 are off the shelf multi antigen targeted car 19, NK cell product candidate for B cell malignancies.

Leering Orion de applications with the FDA for F T 538.

The first ever CRISPR edited I P. S derived cell therapy as well as for F. T 819.

The first ever I P S derived car T cell therapy.

And we informing and launching a transformative partnership with Janssen, bringing together our industry, leading I P. S. C plot product platform with Janssen proprietary tumor targeting antigen binders to develop novel off the shelf current Kay and car T cell immunotherapies for both teams.

Got a watch malignancies in solid tumors.

We also continue to leverage the significant advantages that come with controlling our own in house GMP manufacturing operation as we produced hundreds of Cryopreserved infusion ready doses of our product candidates, which are now stored in inventory and our available off the shelf for.

And our clinical studies.

And although the cobot 19 pandemic has slowed the cadence of new clinical site initiation and patient enrollment introducing some uncertainty with respect to our projected timelines for study enrollment and data read outs, we have successfully opened new clinical sites and initiate enrollment.

Scott Washko: And although the COVID-19 pandemic has slowed the pace of new clinical site initiation and patient enrollment, introducing some uncertainty with respect to our projected timelines for study enrollment and data readout. We have successfully opened new clinical sites and initiated enrollment at these new sites during the past quarter. In March, the first patient was treated in our multi-center phase one clinical trial of FT519, an off-the-shelf, IPS-derived, CAR and K-cell product candidate for patients with B-cell malignancy. FT-596 is our first product candidate that fully leverages the unparalleled advantages afforded by our proprietary IPSC product platform made from a multiplexed engineered clonal master IPS cell line. FT596 is the industry's first cellular immunotherapy that incorporates three active anti-tumor modalities and is currently designed to target multiple tumor-associated antigens expressed on cancerous B cells for best-in-class treatment, in addition to a proprietary car targeting CD19. FT596 expresses our novel, high-affinity, non-cleavable CD16FC receptor, enabling targeting of additional tumor-associated antigens, such as CD20.

These new sites during the past quarter.

In March the first patient was treated on our multi center phase one clinical trial of that T. Five during sex are off the shelf I P. S derived core NK cell product candidate for patients with B cell malignancies.

I have 2596 is our first product candidate.

That's fully leverage is the on parallel the advantages afforded by our proprietary I P. S C product platform.

Made from a multiplexed engineered clone or master I P. S cell line F. T 596 is the industry's first cellular immunotherapy that incorporates three acted anti tumor modalities.

And is currently designed to target multiple tumor associated antigens expressed on cancerous b cells for best in class potential.

In addition to a proprietary car targeting CD 19.

F. T 596 expresses our novel high affinity non cleavable CD Sixteena FC receptor, enabling targeting of additional tumor associated antigens, such as CD 20.

Scott Washko: FT596 also expresses a novel IL-15 receptor fusion, a potent cytokine complex that promotes survival, proliferation, and transactivation of NK cells and CD8 T cells, eliminating the need for systemic cytokine support. Early indications of best-in-class potential of FT-596 were observed at the lowest dose level in our Phase 1 clinical study, where we reported the Day 29 response assessments for the first two patients, each of whom was treated with a single dose of FT-596 as a monotherapy for Relapse Refractory Large B-cell Lymphoma. Not unexpectedly, the first patient, who had most recently relapsed following treatment with an FDA-approved CD19-targeting CAR T-cell therapy, had progressed. The second patient, however, achieved a partial response following treatment with a single dose of FT-596 as a monotherapy at the low-dose level of 30 million cells. The FT-596 response assessment showed a greater than 70% reduction in metabolic activity and a greater than 50% reduction in tumor size as assessed by PET-CT. Notably, the responding patient was most recently refractory to an ex vivo expanded healthy donor derived peripheral blood NK cell therapy.

A few Fivenine six also expressed as a novel I O 15 receptor fusion, a potent cytokine complex that promote survival proliferation, and transacted nation, and NK cells and Cdeight T cells, eliminating the need for systemic cytokine support.

Early indications of best in class potential all that T 596 were observed at the lowest dose level in our phase one clinical study.

Where we reported the day 29 response assessments for the first two patients each of which was treated with a single dose of that T 596, as a monotherapy for relapsed refractory diffuse large b cell lymphoma.

Not unexpectedly the first patient who was most recently relapsed following treatment with an FDA approved cdnineteen targeting car T cell therapy had progressive disease.

The second patient however, achieved a partial response.

Following treatment with a single dose of F. T 596, as a monotherapy at the low dose level of 30 million cells.

The F. T 596 response assessment showed a greater than 70% reduction in metabolic activity and a greater than 50% reduction in tumor size as assessed by pets CP scan.

Notably the responding patient was most recently refractory twin ex vivo expanded healthy donor derived peripheral blood and pay cell therapy.

Scott Washko: Importantly, no dose-limiting toxicities, no FT-596-related serious adverse events, and no events of cytokine release syndrome, neurotoxicity, or graft-first host disease were reported by investigators in either patient. I am pleased to announce that the third patient has been treated with FT-596 at the lowest dose level in our Phase I clinical study, and that the patient successfully cleared the dose-limiting toxicity assessment period. This event is significant, as it enabled us to initiate enrollment of patients in a second treatment regimen of our phase one clinical study, the assessment of FT596 in combination with anti-CD20 monoclonal antibody retoxification.

Importantly, no dose limiting toxicities, no aktiv 596 related serious adverse events and no events of cytokine release syndrome, neuro toxicity or graft versus host disease were reported by investigators in either patient.

I'm pleased to announce that the third patient has been treated with up to 596 at the lowest dose level in our phase one clinical study.

And that the patient successfully cleared the dose limiting toxicity assessment period.

This event is significant as it enables us to initiate enrollment of patients in a second treatment regimen of our phase one clinical study the assessment of that T 596 in combination with the anti Cdtwenty monoclonal any body return.

So Matt.

Scott Washko: Recall that in the universe of CAR-19 cell-based cancer immunotherapy. FT596 offers unique therapeutic potential, as the product candidate's engineered HNCD16FC receptor is specifically designed to augment the anti-tumor activity of monoclonal antibody therapy. Therefore, FT-596 not only has the potential to improve the therapeutic activity of rituximab, but it also enables dual antigen targeting of CD19 and CD20 expressed on cancerous b-cells. We believe combining FT-596 with rituximab is a highly differentiated therapeutic strategy, one that may lead to deeper, more durable responses for patients, and one that may enable FT-596 to be positioned in early line therapy where rituximab-containing regimens are used as standard of care for the treatment of B cell malignancies. Enrollment into this dose-escalating combination regimen of FT596 and rituximab has been initiated at 30 million cells for patients with relapsed refractory B-cell lymphoma. In addition, we are working with investigators from the Masonic Cancer Center, University of Minnesota, to initiate enrollment in a second phase one clinical trial of FT-596 for relapse prevention in patients undergoing an autologous hematopoietic stem cell transplant for the treatment of non-Hodgkin's lymphoma who are at high risk of early relapse.

Recall that in the universe of core 19 cell based cancer Immunotherapies.

T 596 offers unique therapeutic potential as the product candidates engineered H. and CD 16 FC receptor is specifically designed to augment the anti tumor activity of monoclonal antibody therapy.

Therefore F. T 596, not only has the potential to improve the therapeutic activity up were talks about it.

It enables dual antigen targeting of Cdnineteen and Cdtwenty expressed on cancerous b cells.

We believe combining F 30, 596 with Rituximab is a highly differentiated therapeutic strategy.

One that may lead to deeper more durable responses for patients and one that may enable F. T 596 to be positioned in early long therapy, where rituximab containing regimens are used to standard of care for the treatment of B cell malignancies.

Enrollment into this dose escalating combination regimen that T 596, and Rituximab has been initiated at 30 million sells for patients with relapsed refractory b cell lymphoma.

In addition, we're working with investigators from the Masonic Cancer Center University of Minnesota to initiate enrollment in a second phase one clinical trial that key fivenine six four relapse prevention in patients undergoing autologous hematopoietic stem cell transplant.

For the treatment of non Hodgkin's lymphoma, who were at high risk of early relapse.

In the second quarter, we successfully expanded the clinical application of our proprietary IP FC product platform to multiple myeloma.

Scott Washko: In the second quarter, we successfully expanded the clinical application of our proprietary iPSC product platform to multiple myeloma, where rates of relapse remain high and where clinical data suggest that deficiencies in NK cell-mediated immunity, which are evident even at the earliest stages of disease, continue to accumulate through disease progression. We submitted and cleared with the FDA our IND application for FT-538. Our off-the-shelf NK cell product candidate derived from a clonal master iPSC line engineered with three functional components to Enhance Innate Immunity, a novel HN-CD16FC receptor, an IL-15 receptor fusion, and the elimination of CD38 expression to mitigate anti-CD38 antibody-mediated fracture.

Where rates of relapse remain high and.

And where clinical data suggest that deficiencies in NK cell mediated immunity, what's your evident even at the earliest stages of disease continue to accumulate through disease progression.

We submitted in cleared with the FDA, our R&D application for F. T 538.

Our off the shelf NK cell product candidate derived from a clone all master I P. S. C line engineered with three functional components to enhance innate immunity.

A novel HSN, Cdsixteen FC receptor and I'll 15 receptor fusion and the elimination of CD 38 expression to mitigate anti CD 38 antibody mediated fratricide.

We believe the administration of 50 538 to patients can restore innate immunity and that the anti cancer effective certain standard of care treatments in multiple myeloma, including anti Cdthirty eight monoclonal antibodies can be more effective when combined with the.

Scott Washko: We believe the administration of FT538 to patients can restore innate immunity, and that the anti-cancer effect of certain standard of care treatments for multiple myeloma, including anti-CD38 monoclonal antibodies, can be more effective when combined with the engineered functionality of FT538. The multicenter dose escalation phase 1 clinical trial of FT538 is designed to assess the safety and efficacy of three once-weekly doses of FT538 in up to four dose cohorts, starting at 100 million cells per dose. The study will assess two treatment regimens, regimen A as a monotherapy for patients with relapsed refractory AML, and regimen B in combination with daratumumab, an FDA-approved anti-CD38 monoclonal antibody for patients with relapsed refractory multiple myeloma.

Engineered functionality that T 538.

The multi center dose escalation phase one clinical trial that T. 538 is designed to assess the safety and efficacy of three once weekly doses of F. T 538 in up to four dose cohorts starting at 100.

<unk> million cells per dose.

The study will assess to treatment regimens regimen as a monotherapy for patients with relapsed refractory AML.

And regimen be in combination with Daratumumab and FDIC approved anti Cdthirty eight monoclonal antibody for patients with relapsed refractory multiple myeloma.

We plan to initiate patient enrollment and the F 35, 38 phase one clinical trial in the fourth quarter of this year.

Scott Washko: We plan to initiate patient enrollment in the FT-538 Phase I clinical trial in the fourth quarter of this year, to support clinical investigation. FT-538 is a drug product manufactured from a clonal master-engineered IPS cell line, which is renewably used as starting material for routine manufacture of FT-538. The clonal iPS cell line was made by sourcing cells originally from a healthy donor and reprogramming and engineering the cells to induce pluripotency using a proprietary non-integrating system and to integrate a bisistronic cassette containing HN-CD16 and our IL-15 receptor fusion into the CD38 locus, which resulted in complete disruption of the CD38 program. The first batch of our manufacturing campaign, which was Notably, since we right-sized our fill-finish activity and successfully produced the drug product for dose escalation only, the campaign was not designed to maximize drug product yield.

To support clinical investigation ft, Fivethirty, a drug product was manufactured from a colonial master engineered IPO cell line.

Which is renewably used a starting material for routine manufacturer of ft 538.

The quote all IP, yes cell line was made by sourcing cells originally from a healthy donor.

I'm reprogramming and engineering the cells to induced pluripotent see using a proprietary non integrating system.

And to integrate a by strada cassette containing h. and Cdsixteen and I are I'll 15 receptor fusion into the CD 38, locus, which resulted in complete disruption of the CD 30 18.

The first batch of our manufacturing campaign, which was conducted at small scale.

Produced a total of three times tend to the 11th F 35, 38 NK cells.

Which were filled into over 300 units of Cryopreserved infusion ready drug product.

Notably since we right sized our fill finish activities to successfully produced drug product for dose escalation only.

The campaign was not designed to maximize drug product yield.

We calculated though that the potential yield Oh, the cgmp campaign was on the order of 4.5 times tend to the well.

Scott Washko: We calculated, though, that the potential yield of the CGMP campaign was on the order of 4.5 times 10 to the 12th FT538NK cell, or approximately 15,000 unit doses at a dose of 300 million cells per year. In the second quarter, we also achieved a groundbreaking milestone in the field of cell-based cancer immunotherapy, having filed and cleared with the FDA our IND application for FT819, the world's first off-the-shelf IPSC-derived CAR T-cell therapy. This achievement fulfills an unprecedented journey we began four years ago in our partnership with Memorial Sloan Kettering, led by Dr. Michelle Stadlin, to build upon We designed FT819 to specifically address several limitations associated with the current generation of patient and donor-derived CAR T-cell therapy, incorporating several first-of-kind features into the FTA-819 master-engineered IPS cell line to improve safety and efficacy.

F 35, 38 NK cells.

Or approximately.

1000 unit doses.

Dose of 300 million cells per unit.

In the second quarter, we also achieved a groundbreaking milestone in the field of cell based cancer immunotherapy, having filed in cleared with the FDA. Our R&D application for F. T 819, the world's first off the shelf IP FC derived car T cell therapy.

This achievement fulfills an unprecedented journey, we began four years ago under our partnership with Memorial Sloan Kettering led by Dr. Michel satellite to build upon the revolutionary success of patient derived car T cell therapy and to bring universal off the shelf cart.

He sells to patients.

We designed fts 19 to specifically address several limitations associated with the current generation of patient and donor derived car T cell therapies, incorporating several first of kind features into the FDA 819, Master engineered IPO cell line to improve.

Safety and efficacy.

Scott Washko: These include a novel 1xx car signaling domain which has been shown to extend T-cell effector function without eliciting exhaustion. Also, insertion of the CAR transgene directly into the T-cell receptor alpha constant locus, which has been shown to promote uniform CAR expression and enhanced T cell potency, and, of course, complete bi-allelic disruption of T-cell receptor expression for the prevention of graft-versus-host disease, a potentially life-threatening complication associated with allogeneic T cell therapy.

These include a novel one Xx car signaling domain.

Which has been shown to extend T cell effector function without eliciting exhaustion.

Also insertion of the car transgene directly into the T cell receptor alpha constant locus, which has been shown to promote uniform car expression and enhanced T cell potency.

And of course complete bio REALIC disruption of T cell receptor expression for the prevention of graft versus host disease, a potentially life threatening complications associated with allogeneic T cell therapy.

Our ft 819 clinical trial design is robust and innovative.

Scott Washko: Our FT819 clinical trial design is robust and innovative. The Multi-Center Phase I Clinical Trial is designed to assess the safety and activity of FT-819 across three types of B-cell malignancies, chronic lymphocytic leukemia, acute lymphoblastic leukemia, and non-Hodgkin lymphoma. Notably, each indication will enroll independently, and each indication will evaluate three-dose escalating treatment regimens, with regimen A as a single dose starting at 90 million cells. Regimen B as a single dose, starting at 90 million cells with IL-2 cytokine support, and Regimen C as three fractionated doses, starting at 90 million, sorry, starting at 30 million cells.

The multi center phase one clinical trial is designed to assess the safety in activity of ft 819 across three types of B cell malignancies.

Chronic lymphocytic leukemia.

Cute lymphoblastic leukemia, and non Hodgkin lymphoma.

Notably each indication will enroll independently.

And each indication will evaluate three dose escalating treatment regimens.

Regimen, a as a single dose starting at 90 million cells.

Regimen be as a single dose starting at 90 million cells with aisle to cytokine support.

And regimen see as three fractionated doses, starting at 90 million sorry, starting at 30 million cells each.

We plan to initiate patient enrollment in the Ft 819 phase one clinical trial in the fourth quarter of this year.

Scott Washko: We plan to initiate patient enrollment in the FT819 Phase 1 clinical trial in the fourth quarter of this year. Additionally, we highlighted one of the most profound advantages of our proprietary IPSC product platform, our ability to perform complex genetic engineering, including further engineering of an already established Clonal Master-Engineered IPSC Line. Specifically, we demonstrated the use of an already established Clonal Master Salon, further engineering of that line to introduce additional functional elements, selection of a new engineered IPSC clone, incorporating both the original and the additional functional elements, and the creation of a new clonal multiplexed engineered IPS cell line.

At the American Society of gene and cell therapy virtual annual meeting in May.

We highlighted one of the most profound advantages of our proprietary IP FC product platform.

Our ability to perform complex genetic engineering.

Including further engineering.

An already established colonial Master engineered IP FC line.

Specifically, we demonstrated the use of an already established colonial master cell line.

Further engineering on that line to introduce additional functional elements.

Selection of they knew engineered IP FC clone, incorporating both the original and the additional functional elements and the creation of they knew colonial multiplexed engineered IPO cell line.

This is an unparalleled feet.

Scott Washko: This is an unparalleled feat, one that is uniquely enabled by IPS cell technology and enables the building of multiplexed engineered cell products of increasing complexity on top of core engineered functionality. We are applying this approach to rapidly innovate and to efficiently create next-generation product candidates, such as FT-576, as well as new product candidates, such as FT-5-3, specifically for FT5. We presented preclinical data at ASGCT demonstrating the further engineering of our already established master cell line for FT538, which incorporates three functional elements to enhance innate immunity. We introduced a fourth functional element, a car targeting BCMA, to create a clonal mastered and engineered IPSC line for FT576, which is an off-the-shelf multi-antigen targeted. Carb-CMA and K-Cell product candidate for multiple myeloma, analogous to FT-596 in lymphoma.

One that is uniquely enabled by Ikea cell technology and enables the building of multiplexed engineered cell products of increasing complexity on top of core engineered functionality.

We are applying this approach to rapidly innovate.

And to efficiently create next generation product candidates such as F. T 576.

Well as new product candidates such as F. T five three sex.

Specifically for F. 30, 576, we presented preclinical data at Ash GCT demonstrating the further engineering of our already established master cell line for F. T 538.

Which incorporates three functional elements to enhance innate immunity.

We introduced a fourth functional element a car targeting bcm may.

To create a cuomo mastered in engineered IPO C line for F. T 576.

Our off the shelf multi antigen targeted car bcm, a NK cell product candidate for multiple myeloma.

Analogous to F T 596 in lymphoma.

Scott Washko: FT576 is uniquely designed to target multiple tumor-associated antibodies expressed on multiple myeloma cells for best-in-class care. We remain on track to submit our IND application for FT-576 in the fourth quarter. At ASGCT, we also introduced a new product candidate, FT5365, built off of the clonal master-engineered IPSC line for FT-538. FT-536 is engineered with a fourth functional element. A CAR targeting the stress-inducible cell surface proteins MYC-A and MYC-B, which are selectively expressed at high levels on many solid tumors. The NK cell activating receptor NKG2D can recognize and engage stress ligands on tumor cells. The shedding of stress ligands is a common escape mechanism deployed by many tumors to avoid NK cell-mediated immunity and overcome Tumor Escape.

50, 576 is uniquely designed to target multiple tumor associated antigens and expressed on multiple myeloma sells for best in class potential.

We remain on track to submit our R&D application for F. T 576 in the fourth quarter.

And I ask GCT, we also introduced a new product candidate at T. Five three sex.

Built off of the colonial Master engineered IP S. C line for F. T 538.

F. T 536 is engineered with a fourth functional element.

A car targeting the stress inducible cell surface proteins mid gay and make b.

What's your selectively expressed at high levels on many solid tumors.

While the NK cell activating receptor and kg to de to recognize and engage stress logins on tumor cells.

The shedding of stress lie gans is a common escape mechanism deployed by many tumors to avoid NK cell mediated immunity.

To overcome tumor escape.

Scott Washko: Our novel car design uniquely targets a specific region of McCay-McBee, the Alpha 3 domain, which has been shown to remain on tumor cells post-shedding. In fact, a recent publication in cancer immunology research by investigators from Dana-Farber Cancer Institute demonstrated that cancers with loss of MHC class 1 expression can be effectively targeted with alpha-3 domain-specific antibodies to restore NK cell-mediated immunity. We believe the targeting of the alpha-3 domain of MYC-A and MYC-B is a novel and exciting pan-tumor targeting strategy, including and especially for certain solid tumors resistant to cytotoxic T-cells.

Our novel car design uniquely targets, a specific region of Mickey Mcbee, the alpha three domain.

Which has been shown to remain on tumor cells post shutting.

In fact, a recent publication in cancer Immunology research by investigators from Dana Farber Cancer Institute demonstrated that cancers with loss of MHC class one expression can be effectively targeted without the threed domain specific antibodies to restore.

NK cell mediated immunity.

We believe the targeting of the Alpha three domain of Mic gaming B is a novel and exciting pan tumor targeting strategy, including and especially for certain solid tumors resistant to cytotoxic T cells.

We're also leveraging our unique ability to build multiplexed engineered cell products of increasing complexity.

Scott Washko: We are also leveraging our unique ability to build multiplexed engineered cell products of increasing complexity, using already established clonal master-engineered IPSC lines with our collaboration partners, including under our newly formed collaboration with JAMF, which brings together Janssen's deep domain expertise in oncology and our industry-leading IPSL product platform. We have successfully launched this collaboration with strong momentum. Janssen has already contributed proprietary antigen binding domains against one hematologic malignancy target and One Solid Tumor Target, for which we're building novel car content.

I using already established clonal master engineered IP SC lines with our collaboration partners.

Including under our newly formed collaboration with Janssen.

Which brings together janssens deep domain expertise in oncology and our industry, leading IPO cell product platform.

We have successfully launched this collaboration with strong momentum.

Janssen has already contributed proprietary antigen binding domains against one matter logic malignancy target.

And one solid tumor target.

For which we are building novel car constructs.

Scott Washko: As a first step, we are incorporating these constructs into existing multiplexed engineered master IPS cell lines, which may enable an efficient and accelerated pathway to clinical development for the collaboration's initial product. In parallel, we continue to drive innovation, including toward the research and development of next-generation features and functionalities, and for the scaling of our GMP manufacturing processes to support commercial scale operations, as we seek to bring best-in-class, off-the-shelf CAR-NK and CAR-T cell cancer immunotherapies to patients. Turning to our financial results, Revenue was $5.5 million for the second quarter of 2020 compared to $2.8 million for the same period last year.

The first step we're incorporating these constructs into existing multiplexed engineered master IP S. cell lines, which may enable an efficient and accelerated pathway to clinical development for the collaborations initial product cabinets.

In parallel we continue to drive innovation, including toward the research and development of next generation features and functionalities and for the scaling of our GMP manufacturing processes to support commercial scale operations.

As we seek to bring best in class off the shelf car and K and car T cell cancer Immunotherapies to patients.

Turning to our financial results.

Revenue was $5.5 million for the second quarter of 2020 compared to $2.8 million for the same period last year.

Scott Washko: Revenue in the current quarter was derived from our collaboration with Janssen and Ono Pharmaceuticals. Research and development expenses for the second quarter of 2020 were $26.7 million, compared to $21.6 million for the same period last year. The increase in our R&D expenses was attributable primarily to an increase in employee headcount and compensation, including share-based compensation, and expenses associated with the facility lease for our new corporate headquarters. G&A expenses for the second quarter of 2020 were $7.5 million, compared to $5.3 million for the same period last year.

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

Research and development expenses for the second quarter of 2020 or $26.7 million compared to $21.6 million for the same period last year.

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

Gina expenses for the second quarter, 2020 were $7.5 million compared to $5.3 million for the same period last year.

Operator: The increase in our GNA expenses was attributable primarily to an increase in headcount and employee compensation, including share-based compensation, and in legal fees. Total operating expenses for the second quarter of 2020 were $26.9 million, net of non-cash share-based compensation expense of $7.2 million. The company ended the second quarter of 2020 with $533 million of cash, cash equivalents, and investments. Common Stock Outstanding was 86.8 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. I would now like to open up the call to any questions. Thank you. Ladies and gentlemen, as a reminder to ask a question, you will need to press the star and then one on your telephone. To withdraw your question, press the pound key.

The increase in our gene a expenses was attributable primarily to an increase in head count and employee compensation, including share based compensation and in legal fees.

Total operating expenses for the second quarter of 2020 or $26.9 million net of noncash share based compensation expense of $7.2 million.

The company ended the second quarter of 2020 with $533 million of cash cash equivalents and investments.

Common stock outstanding was 86.8 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.

I would now like to open up the call to any questions. Thank you.

Ladies and gentlemen, as a reminder to asked the question you would need to press Star then one on your telephone.

George Your question press the pound cake.

Operator: Again, that's star number one to ask the question. Please stand by while we compile the Q&A roster. Our first question comes from the line of Robin Canacas with Truist Security. Your line is open.

Again that start to ask the question.

Please standby, while we compile the Q.

Our first question comes from the line of Robin Conoco Truest Security Your line is open.

Okay.

Operator: Okay. Thank you so much for taking my question and congratulations on all the progress. Now that the IND for F538 is approved and you're talking about going into AML and multiple myeloma with, you know, you've talked about going into multiple myeloma even before, is it mainly as Darzalex combinations? And also, you mentioned FT576 with the BCMA CAR. So from a, you know, longer-term vision, how are you thinking about your approach to multiple myeloma using these multiple drugs and the multiple combinations? Ladies and gentlemen, please stand by.

Thank you so much for taking my question.

Yes, and all the progress.

No that.

Correct.

It is approved and you're talking about.

Going into an island multiple myeloma.

You've talked about going into multiple myeloma, even before is it mainly as darzalex combinations.

And I'll show you mentioned at T 576, with the Bcm a car so from a.

Longer term.

Vision, how are you thinking about your approach to multiple myeloma using these multiple drugs and the much in combination.

Ladies and gentlemen, please standby.

You May proceed.

Operator: You may proceed. Hi, sorry about that.

Hi, sorry about that.

No.

Scott Washko: Don't worry. You may ask your question again. Oh, thank you. So now that the IND for FT-538 is approved, and you're talking about going into multiple myelomas, I was just wondering about your strategy, given that you also have FT-576, which has a BCMA CAR. Are you thinking mainly in terms of Darzalex combined with FT-538? What is your...big picture strategy for targeting multiple myelomas using multiple drugs and multiple combinations? Absolutely. It's a great question.

You May ask your question again.

Oh.

Thank you.

Now I'd.

Hi, 38 is a true and you are talking about going into much myeloma.

I would just wondering about your strategy given that you also have ft, 576, which has a BPMI car.

Are you seeing you thinking mainly in terms of Darzalex combination with that keep by 38, what does dealer.

Big Pictures strategy for targeting multiple myeloma, using multiple jobs and much of the combinations.

Absolutely.

It's a great question, so keep in mind as well 50 538.

Scott Washko: So keep in mind as well, FT538, is also in a clinical study. One of the arms of the study is also AML. And we're very excited about FT538 being in a monotherapy arm in AML, given the three functional elements that we've engineered into FT538 and its potential activity in AML. As it relates to myeloma, yes, I mean, you touched on it; we're very interested in the potential of FT538 to combine with Darzalex and enhance the antitumor activity of Darzalex, but certainly very analogous to the lymphoma setting. We do believe ultimately that best-in-class potential, potentially, especially in myeloma, is going to require dual antigen targeting. And so, ultimately, the product candidate, as we think about it today, for myeloma, if we continue to strive for innovation and best-in-class potential, you have to assume, in my mind, in our minds, that dual antigen targeting is going to be very critical. So, you know, as we sit here today, I would tell you, ultimately, the product candidate for multiple myeloma is, in fact, 573. Great Thank you. And if I can sneak in one more question,

Is also in a clinical study.

One of the arms of the study is also AML.

And we're very excited about 50 538 being in a monotherapy arm in any ml given the three functional elements that we've engineered into ft, 538, and the potential activity in AML.

As it relates to myeloma, yes, I mean, you touched on it.

We're very interested in the potential of 50 538 to combine with Darzalex and enhance the antitumor activity of Darzalex, but certainly very analogous to the lymphoma setting we do believe ultimately that best in class potential on potentially especially.

In myeloma is going to require dual antigen targeting and so ultimately the product candidate as we think about it today.

For myeloma.

If we continue to strive for innovation and best in class potential you have to assume in my mind in our mind that dual antigen targeting is going to be very critical so as we sit here today I would tell you ultimately the product candidate for multiple myeloma is in fact fiveseven sex.

Great. Thank you and if I can sneak in one last question. So for Ft. Fivenine takes can you maybe talk to us about where you are with respect to recruitment and when we can expect a data update I know you mentioned earlier that you don't want is.

Scott Washko: So for ST596, can you maybe talk to us about where you are with respect to recruitment and when we can expect a data update? I know you mentioned earlier that you don't want to, you know, you want to have a substantial number of patients before you present the data. Can you provide us with some timeline for when we could see some data from DLBCL?

You want to have a substantial number of patients before you presented the data so.

Can you provide us with some timeline for when we could see some data from Bcf.

Yeah, absolutely so I mean.

Scott Washko: Yeah, absolutely. On this call, we obviously indicated that 596 has progressed into a dose escalation arm in combination with rituximab. I think from my perspective, we said on the last call, and we've been pretty consistent about this, we're not going to disclose data patient by patient. We want to have a meaningful dose cohort through escalation to describe data. And we'll give you sort of a heads up on when we think we're going to disclose that, but we will not be doing it on these financial update calls.

On this call will obviously indicated that 596 has progressed into a dose escalation arm in combination with Rituximab I think from my perspective, we set on the last call and we've been pretty consistent about this we're not going to disclose data patient by patient we want to have a meaningful dose cohorts.

Through escalation to decide to describe data.

I will give sort of heads up on when we think we're going to disclose that we will not be doing it on these financial update calls we will do it in conjunction with medical conferences and accepted abstracts or in conjunction with investor events.

Scott Washko: We will do it in conjunction with medical conferences and accepted abstracts or in conjunction with investor events. Generally, I would make the comment that I think we will have a tremendous amount of data coming out over the next 6, 9, 12 months across the company. I mean, at this point in time, the company has five different products with cleared INDs. And I think if you total up the number of arms in our studies, we probably have close to 20 different arms that are running or will be launched before the end of this year. Great, thank you so much for taking my question. I'll get back to you in a moment.

Generally I would make a comment I think we will have a tremendous amount of data coming out over the next six 912 months across the company I mean at this point in time the company has.

Five different products with cleared on Sundays and I think if you total up the number of arms in our studies, we probably have close to 20 different arms.

Thank you running that are running or will be launched.

Before the end of this year.

Great. Thank you so much for taking my question I'll get back in the Q.

Thank you.

Operator: Thank you. Our next question comes from the line of Michael Schmidt with Guggenheim, Guggenheim Security. Your line is open. Hey, this is Kelsey.

Next question comes from the mine of Michael Schmidt with Guggenheim Guggenheim Securities. Your line is open.

Hey, this is kelcy on the Michael Thanks for taking my questions.

Operator: I'm from Michael. Thanks for taking our questions. I just have two quick ones. First, while it's too early to tell based on the first patient treated with FT-596, I guess we've seen from allergy in a similar situation where prior CAR-T non-responders or suboptimal responders maybe don't respond well to a second cell therapy. I'm just wondering maybe what your thoughts are on this potential subpopulation of CAR-T resistant patients. And then for FT-596, also, in terms of the design, I guess there was room to potentially get this amended later on where you could do more than just one treatment. I guess, what are your thoughts around what needs to be shown and how many patients do you think you'll need to show this in to get the protocol amendment? Thank you.

Glenn.

First while it's too early to tell based on the first patient treatment.

Nine six I guess, you've seen from Algenist similar situation, where prior card key non responders or suboptimal responders any don't respond well to a second cell therapy I'm just wondering maybe what your thoughts are on this maybe.

And just some population at Pirquitas inpatient and then for F. 35, Ninetyk also in terms of bit design.

I guess, there wasn't going to potentially get this amended later on where you could do more than just.

Treatment I guess.

What are your thoughts around what needs to be shown and and how many patients you think you'll need to show lists and to get the protocol Amendment.

Thank you sure sure.

Scott Washko: Sure. Sure. Absolutely.

Absolutely.

Scott Washko: So with respect to redosing, the current protocol actually does allow us to work with the FDA at the end of the first treatment cycle to redose patients, and we certainly plan to do that with FT596. And so as patients progress through the first cycle and come to the end of the first cycle, if we believe there's potential benefit to providing patients with a second dose, and the PI and physician, the PI, and the patient support that, we're absolutely expecting to work with the FDA to enable additional doses for patients to continue to deliver and hope to deliver additional benefit. And so that's what we're thinking about redosing.

So with risk with respect to reducing the current protocol actually does allow us to work with the FDA at the end of the first treatment cycle to read dose patients and we certainly planned to be doing to do that with F. T 596, and so.

As patients progress through the first cycle income to the end of the first cycle. If we believe there's potential benefit to providing patient with the second dose and the pie and physician at the pie in the patient support that we're absolutely.

Expecting to work with the FDA.

To enable additional doses for patients to continue to deliver and hope to deliver additional benefit and so that's what we're thinking about reducing I think our expectation long term, obviously with the cell therapies word dancing is that we do believe in multi dose paradigms generally speaking and with all our.

Scott Washko: I think our expectation long term, obviously with the cell therapies we're advancing, is that we do believe in multi-dose paradigms, generally speaking. And with all our clinical studies so far, we have had multi-dose treatment cycles, including with FT538. And so I think with a little bit of data and working with the FDA, we will formally amend the protocol to enable a multi-dose paradigm with FT596 just like we have with FT500, FT516 and FT538. Sorry, your first question was with respect to resistance that we're seeing in the sort of the CD19 world with patients that have previously been treated with therapy. Yeah, I mean, I think this is, to a certain extent, a very, new and rich area for study, right? There's been, you know, relatively speaking, a very small number of patients that have been treated with CAR-19 T-cell therapy, and very few of those patients have been retreated. So this is a rich area for learning.

Clinical studies, so far we do have multi dose treatment cycles, including with 50 538, and so I think a little with a little bit of data and working with the FDA, we will formally amended the protocol.

To enable a multi multi dose paradigm with ft. Fivenine six just like we have with S&P 550, 516 and ft Fivethirty.

Sorry. Your first question was with respect to resistance that we're seeing in the sort of the Cdnineteen world.

With patients that had previously been treated with therapy, Yeah. I mean, I think this is to a certain extent a very.

A new enrich area for study right. There's been relatively speaking a very small number of patients that have been treated with car 19 T cell therapy and very few of those patients have had been retreated. So this is a.

Rich area for learning I think again, one of the things that we are excited about potentially with 596 because of the dual antigen targeting potential in combination with monoclonal antibody therapy like Rituximab, we may have unique and differentiated potential here to come in with a.

Scott Washko: I think, again, one of the things that we are excited about, potentially with 596, because of the dual antigen targeting potential in combination with monoclonal antibody therapy like rituximab, we may have unique and differentiated potential here to come in with a cell therapy in patients that may be very difficult to treat with sort of a single antigen targeted approach once patients have relapsed or are refractory. And so one of the things that we're interested in looking at, at least initially, in sort of early escalation, is, you know, we're not, we're certainly not enriching for this, but I suspect we will probably enroll one or two patients in dose escalation with FT-596 in combination with rituximab, where the patients may have previously relapsed or been refractory to I think it's actually a real opportunity for us with FT-596. We'll see. Great Thank you, Scott.

Cell therapy in patients that may be very difficult to treat with sort of a single antigen targeted approach once.

Patients have relapse or refractory.

So one of the things that we're interested in looking at least initially in sort of early escalation is you know we're not we're certainly not enriching for this but I suspect we will probably enroll one or two patients in dose escalation with Aptiv 596 in combination with Rituximab, where the patients.

May have previously.

Relapsed or been refractory to cdnineteen targeted therapy.

I think it's actually a real opportunity for us with F. T 596, I mean, we'll we'll see.

Great. Thank you Scott.

Thank you.

Operator: Thank you. Our next question comes from the line of Daina Graybosch with SVB Delivering. Your line is open.

Our next question comes from the line of Dana Grey box, but SDB.

Your line is open.

Awesome. Thank you for the question you guys have to do like two hours for these calls there's a lot of content.

Operator: Awesome. Thank you for the question. You guys are going to have to do, like, two hours for these calls.

Operator: There's a lot of content. Congratulations. Two for me.

Congratulations on two for me I wonder outside of starting that two programs from Janssen if their target. If you have any new learning or changes to the collaboration that you can share and then second question is with all these programs and starting the dual targeting the with your high affinity noncash.

Scott Washko: I wonder, outside of starting the two programs from Janssen, if they're a target, if you have any new learnings or changes from the collaboration that you can share. And then, secondly, with all these programs and starting the dual targeting with your high-affinity, capable CB16 receptor, I wonder how you are thinking about and monitoring any risk from IgG competition with such a high-affinity receptor. Thanks. Sure. On the first one with respect to Janssen, I mean, it's obviously early days.

For both 2016 receptor I wonder how you are thinking about and monitoring any risk from Gigi competition I was such a high affinity receptor. Thanks.

Sure on the on the first one with respect to chance I mean, it's obviously early days, we signed the collaboration in April in the midst of in the midst of coated.

Scott Washko: We signed the collaboration in April in the midst of COVID. We have had dialogue with them for quite some time. So I think we hit the ground running, so to speak, when we launched that collaboration. I think we've made really good progress in mapping out not only what we plan on doing just in terms of initial preclinical development, in terms of potentially fast-tracking certain product candidates, but also, for instance, how we're thinking about innovation together, what additional features and functionality we want to engineer into product candidates, both on the hematologic malignancy side and We've also thought about, obviously, and begun initiating with respect to scaling CMC, and clearly already thinking about commercial scale manufacturing processes and kicking that off. So it's been a good start.

We have had dialogue with them for quite some time. So I think we hit the ground running so to speak when we launch that collaboration I think we've made really good progress in mapping out.

Not only what we plan on doing just in terms of initial preclinical development in in terms of potentially fast tracking certain product candidates, but also including for instance, how we're thinking about innovation together, what additional features and functionality when to engineer into product candidates. Both on the hematologic malignancy in solid tumors.

Side.

We've also thought about obviously in begun initiation with respect to scaling CMC.

And clearly already thinking about commercial scale manufacturing processes and kicking that off so yeah. It's it's been a good starts early but it's been a good start to the collaboration.

Scott Washko: It's early, but it's been a good start to the collaboration. With respect to IGG, I'll let Bob, who is with me here in the room, comment on that, and then Wayne can feel free to jump in as well. Sure. Hi, this is Bob. So one of the things about CD16 is that the dissociation constant where the antibodies tend to be minus six. So it doesn't stick and stay.

With respect to IBG.

I'll, let Bob's with me here in the room I'll, let Bob comment on that and then Wayne can feel free to jump in as well.

Sure.

Hi, This is Bob so one other things about CD sixteena that the dissociation constant with the antibodies tend to minus six so.

It doesn't stick and stay and so all the I genes that are you finding a body in order for them to react with Cdsixteen unique cross linking so you need to interaction of to NK cell, but the antibody what the target itself and so that is the reason why you don't see serum levels of IBG really interfering with cdsixteen.

Bahram Valamehr: And so all the IgGs that you find in your body, in order for them to react with CD16, you need cross-linking. And so you need the interaction of the NK cell with the antibody and the target cell. And so that is the reason why you don't see serum levels of IgG really interfering with CD16. And that's another reason why CD16 is natural biology. We all have it, and that's why you don't have autoimmunity caused by CD16. And so this is why we're very excited about our CD16 platform. It allows for very specific targeting of the cancer cell without eliciting undesired autoimmunity issues. So that's the reason why you don't see competition with serum IgG when it comes to Asian CD16. Wayne, do you have any additional comments on top of that? Wayne, do you have anything you want to add on top of that?

Allergy.

And that's another reason why.

City six is natural biology, we all have it and that's why you don't have auto immunity caused by city 16, and so this is why we're very excited about her city 16 platform.

But also very specific targeting uptick cancer cell without eliciting undesired autoimmunity issues. So that's the reason why you don't see competition with serum IBG when it comes to efficiency 16.

When you have any additional comments on top of the when you have anything you want to add on top of the.

No nothing status follow from my perspective other than when we we administer therapeutic funnel qual antibodies like reduction that Dave because at the cross linking phenomenon, we're taking advantage of that given the especially at the target on on the target tumor cells.

Bahram Valamehr: No, nothing, Tad, from my perspective, other than when we administer therapeutic monoclonal antibodies like rituximab, because of that cross-linking phenomenon, we're taking advantage of that given the expression of the target on the target tumor cells. I mean, yeah, and just to extrapolate on that, I mean, keep in mind, CD16 is naturally occurring biology, and in fact, the high affinity receptor, 15% of us are walking around with a high affinity CD16 receptor. So, and clearly, in the world of monoclonal antibody therapy, as Wayne has alluded to, across multiple different monoclonal antibodies, whether it be Rituxan, Herceptin, Erbitux, It was awesome.

I mean, yeah, and just extrapolate on that I mean, no keep in mind Cdsixteen is naturally occurring biology and in fact, the high affinity receptor, 15% of us or walking around with a high affinity cdsixteen receptor. So.

And clearly in the world of monoclonal antibody therapy as Wayne as alluded to across multiple different monoclonal antibodies, whether it be reduction herceptin erbitux potentially even daratumumab.

The high fit the patients receiving a high affinity door patients that have our or has a high affinity CD 16.

Receptor tend to do well with respect to progression free survival.

Awesome. Thank you.

Bahram Valamehr: Thank you. Thank you. Our next question comes from the line of Mara Goldstein with Mizzou. Great, thank you. Just two questions for me. The first is on 538 and cost.

Sure.

Thank you.

A question comes from Milan.

Goals thing.

Okay.

Thank you.

Questions from me on the first just on on.

Slide 38 and cost is the cost.

Scott Washko: Is the cost per dose going to be consistent with that construct as with the others? And then, secondarily, on FT-536; can you just talk about what the steps are and the timing to go into IND mode for that? Sure. So, with respect to... You know, FT-538, FT-596, 536. I mean, cost and manufacturing. I think the important thing to recognize, which, again, is a bit of a head-scratcher, but, you know, we engineer one time. The starting material is an engineered master cell line, which at some basic level is just the starting material for manufacture. So clearly, we invest a lot of time and energy and preclinical development in making and selecting our master engineered cell line. However, once you do that, you never engineer again.

Justin.

With that construct as with the others and then secondarily.

I guess, it's now ESG 36, and they can you talk about weather. So it's definitely a timing to go into I Indianapolis to that.

Sure so with respect to.

You know ft, 538, Ft, 5965, 36, I mean and cost and manufacturer I think the important thing to recognize which again is a bit of a hedge scratcher, but you know we engineer one time right. We the starting material is an engineered master cell.

In line, which at some basic level is just that starting material for manufacturer. So clearly we invest a lot of time and energy and preclinical development in making and selecting our master engineered cell line. However, once you do that in.

Ever engineer again, so our manufacturing process I mean to be clear our cgmp manufacturing process does not involve engineering.

Scott Washko: So our manufacturing process, I mean to be clear, our CGMP manufacturing process does not involve engineering. And so the cost to manufacture FT-500, as an example, which is non-engineered, versus FT-538, which has three engineering features in it. It's not substantially different. With respect to FT536 and thinking about IND timing, it's a 2021 IND. Okay, great, thank you. Sure. Thank you. Our next question comes from the line of Peter Lawson with Barclays. Your line is open. Hi Scott, thanks for taking my question. Just on the mass of potential data, 5 INDs, 20 arms, what would we or could we see this year?

And so the cost to manufacture F. T 500, as an example, which is not engineered versus F. T 538, which has the reengineering features in it.

It's not substantially different.

Okay. Thank you and then just with respect yeah with respect to with respect to Ft, 536, and thinking about R&D, Tom I Indy timing, it's a 2021 I indeed.

Okay, great. Thank you.

Sure.

Thank you.

Our next question comes from the line of Peter Lawson with Barclays. Your line is open.

Hi, Thanks My question just on the I guess, the massive potential data Fivenine days 20.

What would we could we see this year is that still 50 505, one cents or is that more likely.

Scott Washko: Is that still FT500 and 5-1-6, or is that more likely 1Q, and you know what further data we could see? Yeah, I mean, obviously, you know, historically, we've presented data at CITSI, we've presented data at ASH, and we're going to, you know, look for opportunities to present data. I mean, the one thing I should caveat, to be clear, while, you know, we, our bias is certainly going to wait to have meaningful data with respect to a dose escalation arm, the reality is some of our collaborators are obviously very excited about what we're doing with respect to, for instance, FT-819 and working with Memorial Sloan-Kettering for four years on the first IPS-derived CAR T cell. You know, if, for instance, Michelle Satterlein submits an abstract and wants to talk about the first patient, certainly we're going to avail ourselves of opportunities like that as well.

For Q.

What further data could we see.

Yes, I mean, obviously historically, we've presented data at city, we presented data at Ash and we're going I'll.

Look for opportunities to present data I mean, the one thing I should caveat to be clear while.

We are bias is certainly going to wait.

Meaningful data with respect to a dose escalation.

Harm.

The reality is some of our collaborators are obviously very excited what we're doing with respect to for instance, ft 819, and working with Memorial Sloan Kettering for four years on the first IPO strive car T cell.

If for instance, Michel satellite submits, an abstract and wants to talk about the first patient.

Certainly, we're going to avail ourselves to two opportunities like that as well.

Great. Thank you and then just on the the three dosing fractionated dosing schedule.

Scott Washko: Great, thank you. And then just on the three-dosing, fractionated dosing schedule for... 819, just the rack mail there. Sure, I'll turn that over to Wayne. I mean, Wayne spent a tremendous amount of time working with investigators who have historically pioneered and been at the forefront of autologous CAR-19 T-cell therapy, including discussing the potential for fractionated doses and the value of that. So I'll turn that over to Wayne.

819.

Yes, the racquetball there.

Sure I'll turn that over I'll turn that over to Wayne I mean, Wayne spent a tremendous amount of time working with investigators who have historically pioneered and been at the forefront of autologous Corning team T cell therapy.

Including you know discussing the potential for fractionated doses in the value of that so I'll turn that over to win.

Wayne Chu: Yeah, sure, thanks. So it's a great question. You know, I think that the clinical experience with autologous CD19 CAR-Ts has really been focused on their administration as a single dose. And we know that with a single dose of cells, especially as you dose escalate, there are issues from a safety perspective with cytokine release syndrome and neurotoxicity. And I think one of the liabilities with autologous CD19 CAR-T cells is the fact that the administration of those cells is limited to that single dose. We know from other immunotherapies, specifically some of the T cell recruiting specifics, that you can actually take advantage of dose and schedule to design treatment regimens that not only can maintain efficacy because you are able to deliver meaningful dose levels, but do it in a way that can potentially mitigate toxicity, like reducing the frequency and severity of cytokine release syndrome and neurotoxicity.

Sure. Thanks, So it's a great question I think that.

The clinical experience with autologous Cdnineteen car Ts have really been focused on their administration as a single dose and we know that with a single dose of cells, especially as you dose escalate.

Our issues from a safety perspective, with cytokine release syndrome, and Youre toxicity.

And I think what are the Putin and one of the liabilities with autologous Cdnineteen car T. So the fact that the administration middle cells is limited to that single dose.

We know from other Immunotherapies, specifically some of the T cell recruiting bi specifics that you can actually take advantage of dosing schedule design treatment regimens that not only can maintain efficacy because you are able to deliver meaningful dose levels, but do it in a way that can potentially mid.

Okay toxicity like reducing the frequency and severity of cytokine release syndrome.

Neurotoxicity.

Wayne Chu: In fact, to a certain degree, this was demonstrated by the University of Pennsylvania experience with autologous CD19 CAR-T and B-cell ALL, where they demonstrated that if you fractionate or split a CD19 CAR-T cell dose into three, you actually have evidence of better anti-tumor activity, and more importantly, you have better safety as assessed by frequency and severity. And so we wanted to take that concept and explore it in the context And so the plan is for the study is to not only test a fractionation of FTA-819 but essentially fine-tune the individual day doses such that if it turns out that a step-fractionated regimen indeed delivers on a better safety profile while maintaining efficacy, then that can be established as a treatment regimen paradigm for products such as FTA-819. Thanks so much; thank you for the question. Our next question comes from the line of Matt Biegler with Oppenheimer. Your line is open.

In fact to a certain degree this was demonstrated.

With the University of Pennsylvania, and experience with a target Cdnineteen car T and B cell AOL or date demonstrated that if you fracture or use lit cdnineteen car T cell dose into three you actually have evidence of better antitumor activity and more importantly, you have.

Better safety as assessed by.

The frequency and severity of cytokine release syndrome.

And so we want to take that concept and explore Nick in the context of ft. Eight onenine, primarily because the fact that the way FP one on its manufactured we can actually do this on a very consistent basis such at every patient that's in the world into that regiment can get a split dose of ft. Eight one night.

And so what the plan is for the study is too.

Not only test the fractionation up.

One night, but essentially fine tune the individual date doses.

With that if it turns out at a step fractionated regimen indeed delivers.

On a better safety profile, while maintaining efficacy than that can be established as a treatment regimen paradigm for products such as a tier one night.

Gotcha, Thanks, very much the question yes.

Thank you.

Our next question comes from the line of.

Bachelor Oppenheimer. Your line is open.

Hey, guys. Thanks for taking my questions.

Operator: Hey, guys, thanks for taking my questions. My first question is on the 596 patient with the partial response. As of the last update, I think the investigators were filing for emergency authorization to redose the patient. Can you just confirm if that patient was redosed? I can't confirm that on this call.

I have my first question is on the Fivenine sick patient with the partial response.

As of the last update I think the investigators were filing for emergency authorization to reduce the patient can can you just confirm if that patient was reduced.

No I can't confirm that on this call.

Scott Washko: We've not announced that yet, but we have obviously said historically that we are going to take opportunities to work with the FDA to redose patients to the extent we think additional clinical benefit can be provided and to the extent the physician and treating patient think it's the right course. So we are very much in favor of engaging with the FDA to withdraw patients. I don't think I understood. At least I tried, and I also want to have...

We've not announced that yet we have obviously said historically that we're going to take opportunities to work with the FDA to read dose patients to the extent, we think additional clinical benefit can be provided and to the extent the physician and treating patient think it's the right course, so we're you know.

Very much pro engaging with the FDA to retreat patients.

Okay.

Understood at least I tried.

And now.

I wanted to ask you about the motivation behind the recent Bailey collaboration on you didn't really discussed much on your call today, but but for the al immune defense receptor technology on so at the Ash presentation last year. It didn't look like Theres a lot of.

Scott Washko: I wanted to ask you about the motivation behind the recent Baylor collaboration, which you didn't really discuss much on your call today, but for the alloimmune defense receptor technology. So at the ASH presentation last year, it didn't look like there were a lot of host versus graft responses against the iPSCs, at least for FT500. So are you envisioning this technology as a replacement for preconditioning, or really where do you see it fitting in?

Versus graph responses against the ITC.

At least for 5500. So are you in visiting like this technology as a replacement for Preconditioning are really where do you see it sitting and.

Scott Washko: Yeah, absolutely. And keep in mind, right? NK cells and T cells may behave differently. We don't know that yet, do we?

Yes, absolutely and keep in mind right.

NK cells and T cells may behave differently, we don't know that yet right. So I agree with you I think we're accumulating a substantial amount of data now that suggests that NK cells.

Scott Washko: So I agree with you. I think we're accumulating a substantial amount of data now that suggests that NK cells may have some degree of immune privilege based on all the data that we've seen clinically so far, including in 516 with respect to are there anti-product rejection programs that are emerging, and you know, and K-cells may be uniquely advantaged. And so, you know, quite honestly, we brought this technology in, we first saw this technology over a year ago at ASGCT. It is super interesting technology from my perspective because not only does it serve as a defense mechanism, if you will, but that defense mechanism and the way that those receptors are engineered and designed, they actually serve to activate those cells. So it is a very, very interesting technology, I think as we think long term. You know, there are different approaches and philosophies as people are thinking about cell-based cancer immunotherapy and other cell therapies outside of cancer immunotherapy. And clearly, I would say two things.

May have some degree of immune privilege based on all the data that we've seen clinically so far including in Fysixteen with respect to our there and type product rejection programs that are merging and.

NK cells may be uniquely advantaged.

We don't know about T cells yet.

And so you know quite honestly, we brought this technology and we first solve this technology over a year ago to ask GCT. It is super interesting technology from my perspective, because not only does it sol not only does it serve as a defense mechanism as you will.

If you will but that defense mechanism and the way that that risk those receptors are engineered and designed they actually in defending themselves actually also served to activate the cells. So it's a it's very very interesting technology I think as we think long term.

Theres different approaches in philosophies as people are thinking about cell based cancer immunotherapy and other cell therapies outside of cancer immunotherapy, and clearly I would say two things number one certainly in cell based cancer immunotherapy people have talked about and do condition patients and people have talked about.

Scott Washko: Number one, certainly in cell-based cancer immunotherapy, people have talked about and do condition patients, and people have talked about wanting to condition patients even more and driving extended periods of, for instance, immunosuppression. But I think long-term, especially if you want to be part of an early-line therapy, the idea of heavily conditioning patients and having lengthy times of immunosuppression is absolutely not the direction you want to move in. And number two, as you think about moving beyond cell-based cancer immunotherapy and you start thinking about driving long-term, durable engraftment of cells or replacing tissue, I think creative solutions are going to be required to enable that, and this may be one approach to enable that. Hey Matt, this is Dan.

Wanting to condition patients, even more and drive extended periods of for instance, immunosuppression I think long term, especially if you want to be part of an early line therapy.

Idea of heavily conditioning patients and having lengthy times of immuno suppression is absolutely not the direction you want to move in.

And number two as you think about moving beyond cell based cancer immunotherapy and you start thinking about.

Driving long term durable and grafman of cells are replacing tissue.

I think creative solutions are going to be required to enable that and this may be one approach to enable that.

Hey, Matt This is Dan one one thing to add to that is.

Dan Shoemaker: One thing to add to that is another thing we really like about this technology is that it selectively depletes the alloreactive T-cells while leaving sort of the good T-cells behind that will provide protection against infections and relapse. So it's a much more sophisticated strategy rather than just blowing up the entire T-cell compartment, which certainly will make room for an allergenic product, but there are also some consequences to that too, so that Do you think that makes sense? Thanks for the questions, guys. Thank you. Our next question comes from the line of Dead Jet. [inaudible] This is Wendy Wainwright.

The thing we really like about this technology the it selectively depletes the aloe reactive T cells, while leaving sort of the good T cells behind that will provide protection against infections and relapse. So it's a much more sophisticated strategy rather than just blowing up the entire.

So compartment, which certainly will make room for knowledge and product, but there's also some consequences that too. So that's one of the other things that we really like about this idea.

Makes sense thanks for the questions.

Thank you.

Our next question comes on the line of debt.

Pat.

H.C. Wainwright your line is open.

Hi, guys. Thanks for taking the call.

Okay.

So.

Sort of what kind of durability.

Steve.

Right.

And.

Way that you might it.

And then.

Yeah.

Right.

Yes.

Limited.

Good.

Okay.

Operator: Your line is open, but there was a very long persistence of the CAR-NK cells due to the IL-15 cytokine export that you guys also have. So I'm just thinking, do you think that you might see an enhanced potency just from the addition of rituximab, or do you think that data. Yeah, I think, I think generally, you know... It's too early to know.

Another therapy.

But there was very long.

Okay.

Yeah.

You guys.

So.

Again.

You think that you might see an.

Enhance the yes.

Or.

Do you think that or any other.

Okay.

Thanks.

The data modification.

Or what are your thoughts on.

Yes, I think Jeff I think generally.

It's too early to now I mean, there's there's a lot of speculation even just generally even an autologous car T cell therapy.

Scott Washko: I mean, there's a lot of speculation, even just generally, even in autologous CAR T-cell therapy, which leads to deep, durable responses. Generally, we subscribe to a position that single-dose, long-term persistence is not the answer; there's lots of data to show that persisting in the face of persisting cells, Relapse occurs. So clearly, the idea of just giving one dose and thinking that that one dose is going to lead to durable cures in the majority of patients is not the right therapeutic paradigm. It's not a therapeutic paradigm that exists anywhere in cancer.

Which what leads to.

Deep durable responses.

You know generally we subscribe to it position that single dose long term persistence is not the answer.

There's lots of data to show persisting in the face of persisting cells relapse occurs so clearly the idea of just giving one dose and thinking that that one dose is going to lead to durable cures and the majority of patients.

It to us is not the right therapeutic paradigm, it's not a therapeutic paradigm that exist anywhere in cancer.

And so from our perspective and the platform. We're building we think uniquely enables the idea that you can give multiple doses.

Scott Washko: And so from our perspective and the platform we're building, we think it uniquely enables the idea that you can give multiple doses. And we think giving multiple doses is the right strategy and the right way to go. Essentially, you know, giving, you know, new cells every, call it one, call it every two weeks, once a month, I think is, in our minds, the best way to drive deep, durable responses for cancer. Okay. Yeah, that's something certainly the autologous approaches couldn't do, so that makes sense.

And we think giving multiple doses is the right strategy in the right way to go essentially giving new cells every call. It one call. It every two weeks once a month I think is in our mind, the best way to drive deep durable responses.

Yes.

For cancer.

Okay.

Good.

So.

Great.

Scott Washko: Thanks. Thanks, Scott. Our next question comes from the line of Yigal Nochomovitz with Citigroup. Yeah, hi.

Thanks.

Sure.

Thank you.

Our next question comes from them.

No.

With Citigroup.

Operator: Thanks, Scott, for taking the question. I just wanted to circle back on the commentary around the resistance to the approved CD19 CAR-Ts. If you could just elaborate perhaps on why you believe those two B-cell lymphoma patients that had been treated with the approved CD19 CAR-Ts didn't respond to 516 and 596. You know, was it just a question of too low a dose or perhaps that the FD596 patient needed rituximab as well or maybe that the FD596 patient experienced CD19 antigen loss? And would you have any kind of biomarker strategy to help identify patients that failed the approved CD19 CAR-Ts that could benefit from 596 or 516? Thanks. Yeah, I mean, they're all really good questions.

Yes.

Yes, hi, Thanks, Scott kicking the question.

Just wanted to circle back on the commentary around resistance to the approved Cdnineteen car Keith.

If you could just elaborate perhaps on why you believe the those two b cell lymphoma patients.

That had been treated with the approved Cdnineteen car T Didnt responsive site on fixing platinum sick.

Was it just a question of to lower dose or perhaps they feed paternalistic patient needed for Tonight as well.

Or maybe the.

The statistics station.

Parents, Cdnineteen antigen loss and would you have any kind of biomarker strategy to help identify patients.

Nailed it proves cdnineteen car T that could benefit from.

506, or five Onesix. Thanks, Yes, I mean, they're all super good questions.

Scott Washko: And we are obviously investing a lot of time and energy in thinking about clinical translation and, for instance, assessing, as we move forward, assessing, for instance, CD19 expression levels and what may be contributing to, for instance, relapse and whether or not, for instance, another CD19-targeted strategy alone could overcome that relapse. The other thing I would say is, to be fair, you know, these are early days. And a lot of the data that we're seeing generally, at least with respect to the allogeneic cell therapies, are at what I would consider to be lower doses. I mean, at least for fate therapeutics, we're talking about an N01 at a single administration of 30 million cells, which by any measure is an incredibly low dose. I mean, it's one-tenth of what you would get in an autologous CAR T cell setting. So, you know, I'm a bit cautious here about speculating on what we may be seeing or whether there's a trend here or not.

And we are obviously investing a lot of time in energy and thinking about clinical translation and for instance, assessing.

As as we move forward thinking about assessing for instance, cdnineteen expression levels.

And what may be contributing to for instance, relapse and whether or not for instance, another cdnineteen targeted strategy.

Alone.

Could overcome that relapse I the other thing I would say to be fair.

This is are these are early days and a lot of the data that we're seeing generally.

At least with respect to outlet the allogeneic cell therapies are what I would consider to be lower doses I mean for at least for fate Therapeutics I mean, we're talking about it and a one at a single administration of 30 million cells.

Which by any measure is an incredibly low dose I mean, it's 110th of what you would give.

In an autologous car T cells setting so I'm on the cautious here about speculating on.

What we may be seeing or whether theres a trend here are not clearly, though it's been challenging early on with respect to.

Scott Washko: Clearly, though, you know, it's been challenging early on with respect to coming in and trying to retreat CD19 targeted failures. But I think we have a lot to learn, and we actually view it as an opportunity, especially with dual antigen targeting. Okay. That's very helpful. And then just one housekeeping question.

Coming in and trying to retreat cdnineteen targeted failures.

But but I think we got a lot I think we have a lot to learn and we actually view it as an opportunity, especially with dual antigen targeting.

Got it that's very helpful.

Just one housekeeping question I believe you had submitted an amendment.

Scott Washko: I believe you submitted an amendment to the FDA after the DLT that you've seen in common with Rituxan and 5.1.6 with incomplete neutrophil recovery. Has that amendment been approved? And are you also going to modify the Rituximab dosing for Regimen B with FT-596? The answer to both those questions is yes. So with FT-516, we admittedly probably weren't as careful with the protocol as we potentially could have been, but certainly were with FT-596, such that FT-596 did not require amendment, and FT-516 obviously has now been amended, and we are in fact treating patients at the dose. Great. Thank you so much.

Right.

After the deal TV, you've seen in come with for Tux, and 5.6 being completely over coverage.

Has the has that amendment been approved.

And are you also going to modify that we've touched on that dosing regimen be with.

506.

Yes, the answer to both those questions is yes, so with FC Fivesix with up to 516.

We we admittedly probably weren't as careful with the protocol as we potentially could have been.

But certainly were without T 596, such that 50 596 did not require amendment and 516, obviously has now been amended and we are in fact treating patients in the dose escalation arm with F T 516 and Rituximab.

Great. Thank you so much.

Scott Washko: Sure. Thank you. Our next question comes from the line of Ben Burnett with State School. Your line is open. Hi, this is Kaylee Braza on behalf of Ben Burnett.

Sure.

Thank you.

Our next question comes from them on a been Burnett Stifel. Your line is open.

Hi, This is Kent Riza on for Ben Burnett, Thanks for taking our question.

Operator: Thanks for taking our question. We were just wondering if you could talk a little bit more about the enrollment trends in the FT-596 studies. Particularly, should we expect any differences in the types of patients enrolled in the monotherapy arm versus the combination arms? Thank you.

I'm just wondering if you could talk a little bit more about the enrollment trends into the SP 596 studies.

Particularly should we expect any differences and types of patients enrolled in the monotherapy arm versus the combination arms. Thank you.

Sure so.

Scott Washko: Sure. So I would say all patients are essentially eligible for both arms. So whether it's 596 monotherapy or 596 in combination with rituximab, there's no real difference with respect to eligibility criteria in either arm. Our next question comes from the line of Byron Amen with Jeffreys. Your line is open.

I would say eligible all out all patients are essentially eligible for both farm. So whether it's a five ninesix monotherapy or five ninesix in combination with Rituximab Theres no real difference with respect to eligibility criteria in either.

Thank you.

Thank you.

Our next question comes from Milan, Byron Heyman with Jefferies. Your line is open.

Operator: Yeah, hi guys, thanks for fitting me in. Scott, maybe I'll start with 516. Can you provide an update on the combinations with Velumab and then also what are your plans in terms of the EGFR and HER2 antibodies that you've mentioned previously? Sure, so the 516 with the Velumab study is open. We are likely going to be in a position to treat the first patient with FT-516 and Velumab in the third quarter of this year. I think we want to see a little bit of data with Avelumab before moving on to other additional monoclonal antibodies in solid tumors. Keep in mind that as we think about the true solution, one of the true solutions that might have maximal potential in solid tumors may be a product candidate, for instance, that has the CD16 receptor and can synergize with a monoclonal antibody, like FT516, but might also be engineered with additional features and functionality to hit other targets, for instance, as an example, stress ligands with MYC-A and MYC

Yes, hi, guys. Thanks for fitting me in.

Maybe I'll start with 516.

Provide an update on the combinations with a fellow Matt and then also what are your plans in terms of VGF foreign our two antibodies that you've mentioned previously.

Sure. So 516 with the value Mad studies open we are likely going in a position to treat the first patient with up to 516 in a volume AD in the third quarter.

Of this year I.

I think we want to see a little bit of data with the value Mab.

Before moving onto other additional monoclonal antibodies in solid tumors.

He didn't keep in mind that.

As we think about the true solution one of the true solutions that might have maximal potential in solid tumors may be a product candidate for instance that has the cdsixteen receptor and consider jives with a monoclonal antibody like ft Fysixteen.

What might also be engineered with additional features and functionality to hit other targets for instance, as an example stress logins with Mccain mcbee.

Okay, and then on FP.

Scott Washko: Okay, and then on FT819, can you just talk about the dose ranges you're planning to evaluate? I think you stated earlier in the call that you're starting at 90 million cells. So, where does the dose escalation go up to in terms of cell dose in the Phase 1 trial? And in the NHL and ALL cohorts, are you allowing for a prior CD19 CAR?

One night can you just talk about that dose ranges, you're planning to evaluate I think you've stated earlier in the call that you're starting at 90 million cells.

So what's the word as a dose escalation go up to in terms of cell dose.

In the phase one trial and in the NHL and AOL cohorts are you, allowing for prior.

Cdnineteen car.

So on your last question, yes, we don't necessarily exclude prior therapy it doesn't mean that.

Scott Washko: So on the last question, yes, we don't necessarily exclude prior therapy; it doesn't mean that we won't direct the study to appropriate patients, obviously. So as we learn more about CD19 relapse and failures and what may or may not be the cause of that, and biomarkers, we obviously have the ability to work with investigators to choose an appropriate profile where we think the product can be effective. So, I mean, that's how we're thinking about it with FT-819 and whether to enroll patients or not with respect to previous experience with CD19-targeted therapy. As it relates to dose, the monotherapy arms start at 90 million cells. The fractionated starts at 30 million.

We won't direct the study to appropriate patients obviously, so as we learn more about cdnineteen relapse in failures in what may or may not be the cause of that and Biomarkers. We also we obviously have the ability to work with investigators to choose appropriate pen.

Appropriate at appropriate profile, where we think the product can be effective.

So I mean, that's how we're thinking about it with FDA 19.

Whether to enroll patients or not and with respect to his previous experience with cdnineteen targeted therapy as it relates to dose the monotherapy arms or the monotherapy arm start at 90 million sells the fractionated starts at 30 million from 90 million, we're able to escalate to.

Scott Washko: From 90 million, we're able to escalate to 300 and then step fractionated at 100. And then, um, what subset of T-cells, you know, consists within 819? And then I guess on the IL-2 dosing... Are there any read-throughs from FT500 and the dosing with IL-2 there in terms of just influence on cell kinetics? and whether you have any read-throughs into how 819 will behave with IL-2?

300, and then step fractionated at 100.

And then.

Subset of T cells can fifth.

Within 819, and then I guess on the aisle to dose saying.

Are there any read throughs from S&P 500, and the dosing with aisle to there in terms of just influence on cell kinetics, and whether you have any read throughs into how 819 will behave with I also.

Bahram Valamehr: No, I think, you know, some of our work with cytokines in the T-cell space obviously has come from others in the space, for instance, pill therapy, that are using IL-2 with T-cells. And you know, we do have the ability, in a very controlled way, because everybody, all patients are getting the exact same product because it does come from a clonal master cell line, as opposed to having a tremendous amount of heterogeneity that comes with patient-derived or even donor-derived products. We are able to get a true test of what we think could be interesting PK-PD differences with respect to just a T-cell itself versus a T-cell supported by cytokines. With respect to the phenotype of the T-cells, I'll let Bob talk about that.

No I think some of our work with cytokine in the T cell space, obviously has come from others.

In the space for instance, til therapy that are using aisle to with T cells and we do have the ability in a very controlled way because everybody. All patients are getting the exact same product because it does come from a clonal master cell line as opposed to having tremendous amount of heterogeneity.

It comes with patient derived or even donor derived product.

We are able to get a true test of what we think could be interesting PK PD differences with respect to just a T cell itself versus a T cell supported by cytokine support.

With respect to phenotype of the T cells I'll I'll, let Bob talk about that I mean, it's obviously something we spent a lot of time over the past four years optimizing the phenotype with memorial Sloan Kettering, a Michel satellite.

Bahram Valamehr: I mean, it's obviously something we've spent a lot of time over the past four years optimizing the phenotype with Memorial Sloan-Kettering and Michelle Satterlein on the profile of our T-cells. And Bob can talk a little bit about the preclinical work that we've done with 819 and benchmark it against primary T cells. Sure. Just real quickly, since we've been presenting this work at previous conferences, the product is basically exclusively T lymphocytes that carry the alpha-beta phenotype, and their gene expression profile also suggests that they're very similar to primary CAR-T.

On the profile of our T cells, and Bob can talk a little bit about the preclinical work on that we've done with.

819, and benchmarking it against primary T cells car T cells sure just real quickly since we've been presenting this work in the previous conferences the product is.

Basically exclusively T lymphocytes that carry the alpha beta.

Phenotype and gene expression profile also suggest that they're very similar to primary carty.

Bahram Valamehr: Okay, and then, given you're using, I guess, a sub-therapeutic IL-2 dose, what are your thoughts in terms of influence on regulatory T-cells and on the NK, or, in this case, 819, on the T-cell itself? Do you expect that a subtherapeutic IL dose would lead to activation of T-cells and inhibition of regulatory T-cells? Oh yeah, so that is actually something that you can discern from our previous studies with NK cells, actually, obviously because we've given... IL-2 in the past with donor cells, either going back years with NK100, our donor-derived product, or for instance with FT500 now combining with IL-2 and FT516 combining with IL-2. So yeah, we are able to get a look at what is going on with endogenous NK cells and T cells within the patient and how they respond to IL-2.

Okay and then.

Given you're using I guess, a sub therapeutic aisle to dose what are your thoughts in terms of influence on regulatory T cells and on the NK or in this case eight or nine.

On the T. cell itself.

Do you expect that.

Sub therapeutic aisle dose would lead to activation of T cells, and ambition or regulatory T cells.

Oh, yes. So so that is actually something that you can discern from our previous studies with NK cells actually obviously, because we'd given.

Also in the past.

With donor either going back years donor derived NK 100, or donor derived product or for instance, with 5500 now combining with dial two enough t. fysixteen combining with file too. So yeah. We are able to get a look on what is going on with in Dodge Ines NK cells and T cells within the patient and how they were.

Respond to aisle too I think as you suggest we're giving relatively speaking very low doses of while too and so we have not historically seen much impact on that.

Bahram Valamehr: I think, as you suggest, we're giving, relatively speaking, very low doses of IL-2, and so we have not historically seen much impact on that with respect to, for instance, regulatory T cells, although it's something we're absolutely looking into. Great, thanks for taking my questions. Sure. Thank you. Our next question comes from the line of... Jim Birchamall with Wells Fargo. Your line is open. Yeah, hi guys, congrats on all the progress. 596 to start with.

With respect to for instance, regulatory T cells, although it's something we're absolutely looking at.

Great. Thanks for taking my questions.

Sure.

Thank you.

Our next question comes from the line up.

Jim Burke with Wells Fargo. Your line is open.

Hi, guys. Congrats on all the progress just a few on F. 30, 596 to start with just I Didnt hear it earlier, but what are the plans for dose escalation.

Scott Washko: Just, I didn't hear it earlier, but what are the plans for dose escalation for monotherapy? For monotherapy, where does that dose go, and is there a monotherapy strategy? And then on the Rituxan combo, could you speak to the type of patients that you'll enroll that'll make it easier to tease out the incremental contribution of 596 to Rituxan versus what you'd expect for Rituxan retreatment? Sure, so on point number two, start there. I mean, the criteria for enrollment in this study are that the patients will have already failed at least one Rituxan regimen. And so these patients will certainly have seen Rituxan, will certainly have relapsed or been refractory to a Rituxan regimen. And also, in the literature, I think there are pretty clear publications with respect to inpatients, for instance, that have failed Rituxan and are receiving Rituxan, what does Rituxan look like as a monotherapy to initially benchmark against that. And again, we're not necessarily looking for subtle here, right?

For the monotherapy, where does that dose go and is there a monotherapy strategy.

And then on the reduction combo could you speak to that type of patients that you'll enrolled.

That will make it easier to tease out the incremental contribution of 596 to were toxin versus what you'd expect for were toxin.

Retreatment.

Sure. So on point number two start there I mean, though correct curious certainly for enrollment in this study is that the patients will have already failed at least one rituxan regimen and so these these patients will certainly have seen rituxan, we'll certainly have relapsed or been rich.

Factory to a reduction regimen and also in the literature I think there's pretty clear publications with respect to in patients for instance that have failed or toxin and receiving rituxan. What is were toxin look like as a monotherapy to initially benchmark against that and again, we're not.

Necessarily looking for subtle here right. So if you will if you would expect to treat patients where they were tungsten regimen patients that have failed multiple lines of Rituxan regimens I mean, the response rates are very low and that's certainly not what we're looking here with respect to ft looking for here with respect to ft Fivenine.

Scott Washko: So if you would expect to treat patients with a Rituxan regimen, patients that have failed multiple lines of Rituxan regimens, I mean, the response rates are very low. And that's certainly not what we're looking here with respect to, looking for here with respect to FT596 in combination. We're looking for a pretty profound response. As it relates to the monotherapy arm and where we can go, as you know, when we initially submitted the protocol, we were given a choice of dose escalating one of the arms. And because of the significant benefits that we believe we can bring to patients through dual antigen targeting, we selected initially to dose escalate the 596 arm in combination with rituximab. And once we find the MTD in that arm, we're able to then go back and dose escalate the monotherapy arm.

Six in combination.

We're looking for pretty profound response rates.

As it relates to the monotherapy arm and where where we can go and as you know when we initially submitted the protocol, we were giving a choice of dose escalating one of the arms and because of the significant benefits that we believe we can bring to patients through dual antigen targeting we selected initially today.

Dose escalate the 596 arm in combination with Rituximab and once we find the MTD in that arm were able to then go back and dose escalate the monotherapy arm now given the fact that we have seen activity.

Scott Washko: Now, given the fact that we have seen activity in one of the first two patients as a monotherapy, I think that does provide us an avenue to go back to the FDA early and provides, I think, pretty strong support to have a discussion around now amending to dose escalate the monotherapy arm in parallel with the combination, and that's something we are exploring. Got it. And then maybe just on the multiplex, engineering. As you increase the complexity, are you seeing any impact on the viability or potency of the cells? How do you monitor that to just ensure that you've got it as viable and as potent?

In one of the first two patients as a monotherapy I think that does provide us an avenue to go back to the FDA early.

And provides I think pretty strong support so to have a discussion around now amending two dose escalate the monotherapy arm in parallel with the combination on and that's something we are exploring.

Got it and then maybe just on on the out the multiplex engineering.

As you increase the complexity or are you seeing any impact on viability of or potency the cells or.

How do you monitor to that so just to ensure that you've got as viable and as potent cell population as you increasingly engineer the cells.

Scott Washko: Cell Population as you increasingly engineer the cells. Yeah, I mean, it's a great question. And that's, you know, one of the massive advantages associated with what we do, because you can check for that. You can completely check for that at multiple points in this entire paradigm, and you can do all of it preclinically. So, for instance, if you, for instance, further engineer a master cell line, you can fully characterize that now newly engineered master cell line, as an example. You can do all kinds of characterization before the product candidate ever sees a patient. And that includes, to be really clear, taking that newly engineered master cell line and differentiating it into, for instance, the product candidate, and comparing it against, for instance, the already established master cell line. And so you can do all kinds of really rigorous preclinical studies to really validate the engineering.

Yeah, I mean, it's a great question and it's one of the massive advantages associated with what we do because you can check for that.

You can completely check for that at multiple points in this entire paradigm and you can do all of it preclinically.

So for instance, if you for instance, further engineer a master cell line you can fully characterize that now newly engineered master cell line. As an example, you can do all kinds of characterizations before the product candidate ever see that patient and that includes to be really clear taking that new.

Newly engineered master cell line and differentiating it into for instance, the product candidate and comparing it against for instance, the already established Master cell line and so you can do all kinds of really diligent preclinical studies to really.

Validate the engineering.

Scott Washko: And you can, again, before it ever sees a patient, and you're locking it in at the master cell line level for the product so that every patient is getting it. There's no heterogeneity here from patient to patient, batch to batch with respect to engineering because it's all been locked in at the master cell line level based on extensive preclinical studies, including benchmarking against prior versions of that master cell line. Got it. That's very helpful. Maybe just finally and quickly, Scott, just on the FT596 patient who responded, did you observe persistence of CAR positive cells? For how long or what would you have expected, and did you monitor for that?

And you can again before ever season patient and your locking it in at the Master cell line level for the product so that every patients getting it.

There's no heterogeneity here Theres no heterogeneity here from patient to patient batch to batch with respect to engineering, because it's all been locked in at the Master cell line level based on extensive preclinical study.

Including benchmarking against prior versions of that Master cell line.

Got it that's very helpful. Maybe maybe just finally in quickly Scott just on the Ft 596 patient who responded.

Did you observe persistence of car positive cells and for how long or what would you have expected and did you monitor for that.

Scott Washko: The patient's pretty fresh, obviously, with respect to history, and so we're doing a lot of clinical translational work, obviously, both on patient one and patient two. I mean, we want to learn as much as possible here. I think, look, I mean, generally speaking, 30 million cells, as I said before, is a low dose. Certainly, when you look at the CAR T-cell therapy world, 30 million cells is a low dose. Absent Katie Rosvani's data from MD Anderson, I'm not sure if you would have; if you take that data set away from the universe, I don't think anyone would necessarily expect 30 million cells to be an optimized or efficacious dose.

We are doing.

The patients pretty fresh obviously with respect to history and so we're doing a lot of.

Clinical translational work, obviously, both on patient one patient too I mean, we want to learn as much as possible here I think look I mean, generally speaking 30 million cells as I said before is a low dose certainly when you look at the car T cell therapy land 30 million cells of the low dose.

Absent Kt resolve these data from MD Anderson.

I'm not sure. If you would have that if you take that dataset away from the universe I don't think anyone would necessarily expect 30 million cells to be an optimized or efficacious dose. So we're certainly looking forward to dose escalation moving up the ladder and higher doses and combining with reduction.

Scott Washko: So, you know, we're certainly looking forward to dose escalation, moving up the ladder to higher doses and combining with retoxification. Great. Thanks for taking the questions.

Yes.

Great. Thanks for taking the questions.

Operator: Sure. Thank you. Our next question comes from Alana Felicia Young with Cantor Fitzgerald. So, I guess I just wanted one strategic question, you know. I know you have this Janssen collaboration which seems to be going well. How are you thinking about maybe other kinds of collaborations to leverage such a broad platform that you have?

Sure.

Thank you.

Next question comes from Milan.

Cantor Fitzgerald.

Okay.

Hi, guys. Thanks for taking my questions and congrats on the progress.

So I guess I just want to Ocwen strategic question I know you have this downturn collaboration with things like on well I'm. How are you thinking about maybe other kind of collaboration is the leverage.

[music].

That you have and then I guess.

Scott Washko: And then, I guess, you know, I kind of wanted to just go back and revisit what was the question very early in the queue about kind of differentiation, in particular 576 on the BCMA platform. Is that kind of like kind of the moonshot for targeting BCMA, or maybe not the moonshot, but you're pretty much moving along nicely there. So, those are my two questions.

I kind of wanted just go back.

Some very early in the Q.

About kind of differentiation in particular with high seven six on the VCM. A platform is that is that kind of like kind of headwind shot for targeting.

I may or may be not diminish items that you're pretty much moving along nicely there. So.

Other my two questions. Thanks.

Scott Washko: Sure. So with respect to 576, let's just start there. Look, I think.

Sure.

So with respect with respect to 576, let's just start there look I think.

In others.

Theres or theres differences that we've seen in just so based therapy with lymphoma and myeloma, so far and the data sets a myeloma are emerging south.

Scott Washko: You know, there are the... There are differences that we've seen in just cell-based therapy with lymphoma and myeloma so far. And the data sets in myeloma are still emerging, so I'll be sort of cautious with my comments about myeloma. Clearly, in lymphoma, we've seen cures. We've seen cures with CAR T-cell therapies targeting

Our still emerging so I'll be sort of.

Cautious with my comments in myeloma, but.

Clearly in lymphoma, we've seen cures.

We've seen cures with car T cell therapies targeting cdnineteen.

I'm not sure we've seen that yet.

Scott Washko: I'm not sure we've seen that yet in myeloma with BCMS, as at least single antigen targeting. We'll see what happens when we do dual antigen targeting. And we're not the only ones pursuing dual antigen targeting. But maybe we will drive to deeper, durable responses that enable cures in myeloma. That said, I don't think BCMA is the last target that will emerge in the myeloma space that folks will be excited about. There are other targets beyond BCMA that are certainly emerging that, at least preclinically, look just as exciting, if not more exciting, as compared to, for instance, BCMA. I do think, though, in myeloma, especially, hitting more than one antigen is going to be required if you want to drive.

In myeloma with Bcf.

As at least a single antigen targeting we'll see we'll see what happens when we do dual antigen targeting and we're not the only ones pursuing duly antigen targeting but maybe we will drive to deeper durable responses that enable cures in myeloma.

That said I don't think Bcm may is the last target.

That will emerge in the myeloma space that folks will be excited about there are other targets beyond DCM may that are certainly emerging that at least preclinically looked just as exciting if not more exciting with respect to as compared to for instance Bcf.

I do think though in myeloma, especially more than hitting more than wanting antigen is going to be required if you want to drive for cures.

Scott Washko: I think that's going to be enough. As for your question with respect to other partnerships, yeah, I mean, I agree with you. I mean, we have a very broad platform. There's a lot of opportunity just in cell-based cancer immunotherapy, as well as outside of cell-based cancer immunotherapy. I think iPS cell technology is really starting to catch a lot of folks' attention with respect to its potential and the unique advantages that come with iPS cell technology, especially as it relates to multiplexed NGC. And so, yeah, I think there's, I mean, we're super happy, obviously, with the launch of the Janssen collaboration. But I think there's opportunity for more partnerships, absolutely, including beyond cancer immunotherapy.

Thats going to be necessary.

As it relates to your question with respect as it relates your question with respect to other partnerships. Yeah. I mean I agree with you I mean, we have very broad platform Theres a lot of opportunity just in cell based cancer immunotherapy as well as an outside of cell based cancer immunotherapy.

I think IPO cell technology is really starting to catch a lot of folks attention with respect to its potential in the unique advantages that come with IPO cell technology, especially as it relates to multiplexed engineering.

And so yeah, I think there's I mean, we're super happy obviously with the launch of the Janssen collaboration.

But but I think there's opportunity for more firm for more partnerships absolutely including beyond.

Cancer immunotherapy.

Thank you.

I'm showing no further questions in the Q.

Scott Washko: I'm showing no further questions in the queue. I would now like to turn the call back over to Scott Washko for closing.

Now I'd like to turn the call back over to Scott.

Okay.

Terrific. Thank you everyone I appreciate everybody on the east coast, especially hanging with us through this late hour.

Operator: Thank you, everyone, and I appreciate everybody on the East Coast especially hanging with us through this late hour. I appreciate everybody's participation in today's call and all your continued support and interest in Fate Therapeutics. Be well. Good night. Ladies and gentlemen, this concludes today's conference. Thank you for your participation. You may now disconnect.

Appreciate everybodys participation in today's call and all your continued support interest the fate therapeutics be well good night.

Ladies and gentlemen, this concludes todays conference. Thank you for your participation you may now disconnect everyone have a wonderful.

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