Q3 2019 Earnings Call

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Operator: Copyright 2020, New Thinking Allowed Foundation Welcome to the Fate Therapeutics 3rd Quarter 2019 Financial Results Conference Call. At this time, all participants are in a listen-only mode.

Welcome to the fate Therapeutics third quarter 2019 financial results conference call at.

All participants are not listen only mode.

Operator: This call is being webcast live on the Investors and Media section of Fate's website at www.fatetherapeutics.com. As a reminder, today's call is being recorded. I would now like to introduce Scott Walshco, President and CEO of Fate Therapeutics. Thank you.

This call is being webcast life when investors Nvidia section will face website access therapeutics dotcom.

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

I would now like to introduce Scott Wolchko, President and CEO healthy therapeutics.

Scott Walshco: Good afternoon, and thanks, everyone, for joining us for the Fate Therapeutics 3rd Quarter 2019 Financial Results Call. Shortly after 4 p.m. Eastern Time today, we issued a press release with these results, which can be found in the Investors & Media section of our website under Press Releases. In addition, our Form 10-Q for the quarter ended September 30, 2019, was filed shortly thereafter and can be found on the Investors & Media section of our website under Financial Information. Before we begin, I would like to remind everyone that, except for statements of historical facts, the statements made by management and responses to questions on this conference call are forward-looking statements under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that could 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 third quarter 2019 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 in media section of our web site under press releases in addition.

And our Form 10-Q for the quarter ended Septemberthirty 2019 was filed shortly thereafter and can be found on the investors immediate section of our web site under financial information.

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

These statements involve risks and uncertainties that could cause actual results to differ materially from those in such forward looking statements. Please see the forward looking statement disclaimer on the Companys earnings press release issued after the close of the market today as well as the risk factors in the company's FCC filings incur.

Scott Walshco: 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 September 30, 2019, that was filed with the SEC today. Undue reliance should not be placed on forward-looking statements that 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 Vice President of Clinical Development.

Who did in our Form 10-Q for the quarter ended September 32019 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 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 our Dr., Dan Shoemaker, our Chief Scientific Officer, Dr., Bob Damir, Our Chief Development Officer, and Dr. Wayne Shoe, our vice President of clinical development.

Scott Walshco: Over the past three months, Fate Therapeutics has achieved a series of key milestones that have firmly established the company as the leading manufacturer and developer of off-the-shelf engineered NK cell and T cell cancer immunotherapy and which have enabled the company to generate decisive clinical data across multiple product candidates from our IPSC product platform. These milestones include, one, treatment of the first patient with FT566. FT516 is an off-the-shelf, targeted NK cell cancer immunotherapy derived from a clonal master-induced pluripotent stem cell, or iPSC, line engineered to uniformly express a novel, high-affinity, non-cleavable CD16FC receptor. FT516 is the second product candidate emerging from our IPSC product platform.

Over the past three months fate Therapeutics has achieved a series of key milestones that are firmly establish the company as the leading manufacturer and developer of off the shelf engineered NK cell and T cell cancer immunotherapy.

In which enabled the company to generate decisive clinical data across multiple product candidates from our IP FC product platform.

These milestones include one treatment of the first patient with Ft Fysixteen.

Ft Fysixteen isn't off the shelf targeted NK cell cancer immunotherapy derived from a colonial master induced pluripotent stem cell or IP FC line engineered uniformly express a novel high affinity non cleavable CD Sixteena FC receptor.

Ft 516 is the second product candidate emerging from our IP Assi product platform.

Scott Walshco: And it is the first ever cell product in the world derived from a genetically engineered iPSC line to be administered to a patient. Number two, FDA clearance of our investigational new drug application for FT519. FT596 is an off-the-shelf, iPSC-derived chimeric antigen receptor, or CAR, NK cell cancer immunotherapy that is uniquely designed to engage multiple tumor-associated antigens expressed on cancer cells for best-in-class activity. FT596 is the first-ever cell therapy cleared by the FDA for clinical investigation that is engineered to express three active antitumor functional modalities, and three, Our state-of-the-art facility is custom-designed to use clonal master iPSC lines as a renewable cell source for the manufacture of off-the-shelf allogeneic NK cell and T cell products.

And it is the first ever cell product in the world derived from a genetically engineered IPO C line to be administered to patients.

Number two.

FDIC clearance of our investigational new drug application for Ft Fivenine sex.

50, 596 isn't off the shelf I PSC derived kamerick antigen receptor or car NK cell cancer immunotherapy that is uniquely designed to engage multiple tumor associated antigens expressed on cancer cells for best in class activity.

Ft 596 is the first ever cell therapy cleared by the FDA for clinical investigation that is engineered to express three active antitumor functional modalities.

And three launch of our cgmp facility for the clinical manufacturer of IP asteroids cell therapies.

Our state of the our facility is custom designed to use colonial master I PSC lines as a renewable cell source for the manufacturable off the shelf allogeneic NK cell and T cell products. The facility has been commission and qualified the company has been issued a drug manufacturing licensed by the state.

Scott Walshco: The facility has been commissioned and qualified, and the company has been issued a drug manufacturing license by the state of California. And we have begun clinical manufacture of multiple product candidates within the facility. With our full control of CGMP production, combined with our proven ability to genetically engineer iPSCs and create clonal master iPSC lines qualified for clinical use, we believe we have established operational capabilities unique to the industry to ensure consistent, large-scale, and cost-effective manufacture of off-the-shelf cell products for on-demand delivery to patients. Starting with FT-516.

Out of California, and we have put gone clinical manufacture of multiple product candidates within the facility.

With our full control of cgmp production combined with our proven ability to genetically engineer IP SCS and create colonial master IPO see lines qualified for clinical use we believe we have established operational capabilities unique to the industry to ensure consistent.

Large scale and cost effective manufacturer of off the shelf sell products for on demand delivery to patients.

Starting with Ft, Fysixteen ft, Fysixteen as the first engineered NK cell cancer immunotherapy emerging from our IPO see product platform. The product candidate is derived from a colonial master IPO C line engineered to express a novel high affinity non cleavable CD Sixteena FC receptor.

Scott Walshco: FT-516 is the first engineered NK cell cancer immunotherapy emerging from our iPSC product platform. The product candidate is derived from a clonal master iPSC line engineered to express a novel high-affinity, non-cleavable CD16FC receptor. CD16 is a naturally occurring activating receptor expressed on NK cells, and the receptor has been shown to be the key mediator of antibody-dependent cellular cytotoxicity, or ADCC, which is a potent anti-tumor mechanism by which NK cells recognize, find, and kill antibody-coded tumors. CD16 is most commonly found in its low affinity variant form, and its expression has been shown to undergo considerable downregulation in the tumor microenvironment, which can significantly limit NK cell antitumor activity.

Cdsixteen is a naturally occurring activating receptor expressed on NK cells and the receptor has been shown to be the key mediator of antibody dependent cellular cytotoxicity or ADCC, which is a potent anti tumor mechanism by which NK cells recognize bind and Phil.

Antibody coated tumor cells.

Cdsixteen has most commonly found in its low affinity variant form.

And it's expression has been shown to undergo considerable down regulation in the tumor micro environment, which can significantly limit NK cell antitumor activity.

Scott Walshco: In contrast, the novel CD16FC receptor incorporated into FT516 is comprised of two unique functional enhancers. It is comprised of the high-affinity variant form to enhance binding to tumor-targeting antibodies, and it has been modified to prevent downregulation, which is designed to significantly augment ADT. The FT-516 clinical trial is a multi-dose, phase I clinical trial in which FT-516 is being investigated as a monotherapy for the treatment of relapsed refractory acute myeloid leukemia and as a combination therapy with CD20-directed monoclonal antibodies for the treatment of relapsed refractory B-cell lymphoma. The study is designed to assess the safety and activity of an out Patients who are clinically stable following the first treatment cycle are eligible to receive a second treatment cycle of three once-weekly doses of FT5.

In contrast, the novel CD Sixteena FC receptor incorporated into Ft. Fysixteen is comprised of two unique functional enhancements. It is comprised of the high affinity varian form to enhance binding to tumor targeting antibodies and it has been modified to prevent.

Down regulation.

Which are designed to exist significantly augment ADCC.

The FCC Fysixteen clinical trial is a multi dose phase one clinical trial in which ft 516 is being investigated as a monotherapy for the treatment of relapse refractory acute myeloid leukemia and as a combination therapy with CD 20, directed monoclonal antibodies for the treatment of real.

EPS refractory b cell lymphoma.

The study is designed to assess the safety and activity of an outpatient treatment cycle comprised of three once weekly doses of that T 516.

Patients who are clinically stable following the first treatment cycle are eligible to receive a second treatment cycle of three once weekly doses of 30 516.

Scott Walshco: Importantly, to promote FT516 anti-tumor activity, patients will receive a moderate lymphoconditioning regimen prior to each treatment cycle of FT516, as well as IL-2 cytokine support with each dose of FT516. Both arms of the FT-516 clinical trial are enrolling concurrently. Three dose levels of 90 million, 300 million, and 900 million cells per dose are planned for AML, with the CD20-directed monoclonal antibody combination arm starting at 30 million cells per dose to evaluate safety in a single patient.

Importantly to promote ft, fysixteen antitumor activity patients will receive a moderate lymphoma conditioning regimen prior to each treatment cycle of ft 516.

As well as aisle to cytokine support with each dose of ft Fysixteen.

Both arms of the FC Fysixteen clinical trial are enrolling concurrently three dose levels of 90 million 300 million and 900 million cells per dose are planned for AML.

With the CD 20, directed monoclonal antibody combination arm, starting at 30 million cells per dose to evaluate safety and a single patient.

Scott Walshco: In October, the first patient received FT-516 in combination with rituximab for the treatment of diffuse large B-cell lymphoma, and the second patient in the clinical trial received FT-516 as monotherapy for the treatment of refractory AML. We believe there is compelling clinical proof of concept to support the potential clinical benefit of FT516 for the treatment of AML and as a combination therapy with CD20-directed monoclonal antibodies for the treatment of B-cell lymphoma, and that there are well-established clinical benchmarks against which we can assess safety now. Specifically, in the setting of relapsed refractory AML, hundreds of patients have been treated with donor-derived Notably, leukemic blasts in the bone marrow have been shown to be particularly susceptible to direct NK cell-mediated killing, and complete remission rates ranging from 20 to 35% have been reported in investigator-initiated studies of donor-derived NK cell therapy.

In October the first patient received F. T 516 in combination with Rituximab for the treatment of diffuse large b cell lymphoma.

And the second patient in the clinical trial received two fysixteen as a monotherapy for the treatment of refractory AML.

We believe there is compelling clinical proof of concept to support the potential clinical benefit of F. T 516 for the treatment of AML and as a combination therapy with CD 20, directed monoclonal antibodies for the treatment of B cell lymphoma.

And that there are well established clinical benchmarks against which we can assess safety and efficacy.

Specifically in the setting of relapse refractory AML hundreds of patients have been treated with donor derived NK cell therapy, notably leukemic blast in the bone marrow have been shown to be particularly susceptible to direct NK cell mediated, killing and complete remission rates ranging from 20% to 35% have been report.

Good investigator initiated studies of donor derived NK cell therapy.

Scott Walshco: In addition to bone marrow biopsies to assess clinical anti-leukemic responses to FT-516, we will also collect bone marrow samples before treatment and following the third dose of FT-516 in the first treatment cycle to gain an early read on FT-516 homing to the bone marrow and anti-leukemic activity. In addition to the direct NK cell-mediated killing, numerous clinical studies with FDA-approved tumor-targeting monoclonal antibodies have demonstrated that ADCC is an important mechanism of action that drives the anti-tumor activity of monoclonal antibody therapy. Importantly, these studies have demonstrated that patients homozygous for the CD16 high-affinity variant 158V have significantly improved clinical outcomes following treatment with monoclonal antibody therapy. However, only about 15% of patients are privileged to receive this advantaged CD16 form. In the setting of relapsed refractory B-cell lymphoma, single-agent clinical activity of monoclonal antibodies has shown modest clinical responses, for example, with response rates of approximately 10% and overall response rates of approximately 30% in DLBCL.

In addition to bone marrow biopsies to assess clinical anti leukemic responses to ft. Fysixteen. We will also collect bone marrow samples before treatment and following the third dose of Ft 516 in the first treatment cycle to gain an early read on F. T 516 homing to the bone marrow.

Okay, and anti leukemic activity.

In addition to their direct NK cell mediated killing numerous clinical studies with FDA approved tumor targeting monoclonal antibodies have demonstrated that ADCC is an important mechanism of action that drives the anti tumor activity of monoclonal antibody therapy.

Importantly, these studies have demonstrated that pain patients homozygous for the Cdsixteen high affinity variant 158 D has significantly improved clinical outcomes following treatment with monoclonal antibody therapy. However, only about 15% of patients are privileged with this advantage.

Hi, Cdsixteen form.

In the setting of relapse refractory B cell lymphoma single agent clinical activity of monoclonal antibodies have shown modest clinical responses. For example, with response rates of approximately 10% and overall response rates of approximately 30% in Dl Bcl.

Scott Walshco: Since FT516 incorporates a novel high-affinity 158 variant and is non-cleavable, which prevents down-regulation and maintains active levels of surface expression, we believe FT516 can significantly augment ADCC, resulting in a higher and more durable response. In September, we announced that the FDA cleared our investigational new drug application for FT-596. FT-596 is an off-the-shelf CAR-NK cell cancer immunotherapy derived from a clonal master iPSC line engineered with three anti-tumor functional modalities, a proprietary car that targets the B-cell antigen CD19. The novel high-affinity non-cleavable CD16FC receptor that enables multi-antigen targeting and an IL-15 receptor fusion protein that promotes enhanced NK cell activity.

Since Aptiv Fysixteen incorporates a novel high affinity 158 variant.

Nonclinical and in since it is non cleavable, which prevents down regulation and maintains an active levels of surfaced expression. We believe ft 516 can significantly augment ADCC, resulting in higher and more durable responses.

In September we announced that the FDA cleared our investigational new drug application for F. T 596 ft Fivenine six isn't off the shelf car NK cell cancer immunotherapy derived from a bundle master I PSC line engineered with three antitumor functional modalities upper.

Prior Terry car, but targets the b cell antigen cdnineteen.

The novel High affinity non cleavable CD 16 FC receptor for that enables multi antigen targeting.

And an IL 15 receptor fusion protein that promotes enhanced NK cell activity.

Scott Walshco: FT596 is at the forefront of cell-based cancer immunotherapy. It is the first cell therapy cleared for clinical investigation by the FDA that is engineered with three active anti-tumor components. We believe FT596 is a transformative product candidate and has the potential to supplant patient-specific and allogeneic CAR-19 T-cell immunotherapies that recognize only one antigen and fail to address the significant risk of relapse due to antigen escape. Clinical Experience with Patient-Derived CAR T-Cell, both in the case of single antigen targeting CAR T-cells against CD19 in leukemia and lymphoma, and against BCMA in myeloma, have clearly demonstrated the down-regulation of the target antigen, such as CD19 and BCMA, is a major mechanism of resistance that accounts for failure to respond, and even for those patients that initially respond, failure to achieve long-term, durable remission.

596 is at the forefront of cell based cancer immunotherapy.

It is the first cell therapy cleared for clinical investigation by the FDA that is engineered with three active anti tumor components.

We believe that T 596 is a transformative product candidate and has the potential to supplant patient specific and allogeneic car 19 T cell immunotherapies that recognized only one antigen and failed to address the significant risk of relapse due to antigen escape.

Clinical experience with patient derived car T cells. Both in the case of single antigen targeting car T cells again, cdnineteen inland Kimi and lymphoma and against Bcm may in myeloma have clearly demonstrated that down regulation of the target antigen such as Cdnineteen NBC M&A is a major Mac.

Aneurysm of resistance that accounts for failure to respond and even for those patients that initially respond failure to achieve long term durable remission.

Scott Walshco: FT596 is uniquely designed to target multiple tumor-associated antigens and overcome CD19 antigen escape. In addition to the proprietary CAR-targeting CD19, FT596 expresses the high-affinity non-cleavable CD16-FC receptor, which enables coincident targeting of CD19 and additional tumor-associated antigens in combination with therapeutic antibodies. FT-596 also expresses the IL-15 receptor fusion, a potent cytokine complex that promotes survival, proliferation, and transactivation of endogenous immune cells without the need for systemic cytokine support. Together, these features of FT-596 are intended to maximize potency and improve durability of the research. The Phase I clinical trial is specifically designed to exploit the multi-antigen targeting functionality of FT596 and overcome antigen escape, upon establishing safety as a monotherapy in a first-dose cohort of 30 million cells per dose. The clinical trial will assess the safety and activity of FT596 in combination with rituximab in patients with B-cell lymphoma at four planned dose levels. 30 million, 90 million, 300 million, and 900 million cells per dose.

FC Fivenine six is uniquely designed to target multiple tumor associated antigens and overcome CD 19 antigen escape. In addition to the proprietary car targeting Cdnineteen ft 596 expresses the high affinity non cleavable cdsixteena tier FC receptor, which enables coincide.

In targeting of Cdnineteen and additional tumor associated antigens in combination with therapeutic antibodies.

50, 596 also expresses the IL 15 receptor fusion a potent cytokine complex that promotes survival proliferation and transact division of in Dodge in us immune cells without the need for systemic cytokine support.

Together. These features of F. 30, 596 are intended to maximize potency and improved durability of response.

The phase one clinical trial is specifically designed to exploit the multi antigen targeting functionality of ft, 596, and overcome antigen escape.

So PON, establishing safety as a monotherapy in a first dose cohort of 30 million cells per dose the clinical trial will assess the safety and activity of ft 596 in combination with Rituximab in patients with B cell lymphoma at four.

Planned dose levels 30 million 90 million 300 million and 900 million cells per dose.

Scott Walshco: Additionally, upon establishing the maximum tolerated dose in combination with rituximab, the clinical trial will assess the safety and activity of FT-596 in combination with obinutuzumab in patients with chronic lymphocytic lymkemia. Each patient will receive a moderate outpatient lymphoconditioning regimen prior to the first treatment cycle of FT596, which cycle consists of a single dose of FT-5. Since FT-596 incorporates IL-15 cytokine support as part of its engineered functionality, cytokine support will not be administered to the patient based on the enhanced persistence of FT-596 observed in our preclinical study. Importantly, each patient may be eligible for additional treatment cycles of FT-596 based on evidence of clinical benefit, subject to review of the patient's status by the FDA. At this time, we have finalized the clinical protocol in consultation with leading clinical investigators in the CAR T-cell field.

Additionally, upon establishing the maximum tolerated dose in combination with Rituximab. The clinical trial will assess the safety in activity of F. T 596 in combination with have been a twos AMAG in patients with chronic lymphocytic leukemia.

Each patient will receive a moderate outpatient lymphoma conditioning regimen prior to the first treatment cycle of T 596, which cycle consists of a single dose of ft 596.

Since ft Fivenine six incorporates the IL 15, cytokine support as part of its engineered functionality cytokines support will not be administered to the patient based on enhanced persistence of ft 596 observed in our preclinical studies.

Importantly, each patient may be eligible for additional treatment cycles FFT 596 based on evidence of clinical benefit subject to review of the patient status by the FDA.

At this time, we have finalized the clinical protocol in consultation with leading clinical investigators in the car T cell field.

Scott Walshco: Clinical trial start-up activities have begun at multiple sites, and we are planning for treatment of the first patient in early 2020. We continue to be excited about the multifaceted, direct, and indirect roles of NK cells that they may play in attacking solid tumors. While remarkable responses have been achieved with checkpoint inhibitor therapy across a number of solid tumor types, these therapies are not curative, and in most cases, patients either fail to respond to or progress on these agents. One common mechanism of resistance to checkpoint inhibitor therapy is associated with loss of function mutations in genes critical for antigen presentation, which can result in partial or complete loss of MHC class one expression and escape from T cell antitumor activity.

Clinical trial startup activities have begun at multiple sites and we're planning for treatment of the first patient in early 2020.

We continue to be excited about the multifaceted direct and indirect roles of NK cells that they may play and attacking solid tumors.

While remarkable responses have been achieve with checkpoint inhibitor therapy across a number of solid tumor types. These therapies are not curative and in most cases patients either fail to respond or progress on these agents.

One common mechanism of resistance to checkpoint inhibitor therapy is associated with loss of function mutations in jeans critical for antigen presentation.

Which can result in partial or complete loss of MHC class, one expression and escape from T cell antitumor activity.

Scott Walshco: Compelling biological evidence continues to emerge that supports the potential for NK cells to recognize and directly kill tumors with these mutations and convert checkpoint inhibitor therapy resistant patients into clinical responders. We believe FT500, the first off-the-shelf NK cell product candidate emerging from our iPSC product platform, represents a novel therapeutic strategy to potentially resensitize patients to checkpoint inhibitor therapy and overcome disease resistance. We are currently investigating FT500 in a multi-dose, phase 1 clinical trial for the treatment of advanced solid tumors. The study is designed to assess the safety and activity of three once-weekly doses of FT500 as monotherapy in the salvaged setting of disease and in combination with one of three FDA-approved checkpoint inhibitor therapies in patients whose tumors failed to respond or progressed following initial response with prior checkpoint inhibitor therapies. Patients who are clinically stable following the first cycle of FT500 treatment are eligible to receive a second treatment cycle of three additional once-weekly doses of FT500 for a total of up to six doses at each dose level.

Compelling biological evidence continues to emerge.

Supports the potential for NK cells to recognize and directly kill tumors with these mutations and convert checkpoint inhibitor therapy resistant patients into clinical responders.

We believe ft 500, the first off the shelf NK cell product candidate emerging from our IP FC product platform represents a novel therapeutic strategy to potentially re sensitize patients to checkpoint inhibitor therapy and overcome disease resistance.

We are currently investigating ft 500 in a multi dose phase one clinical trial for the treatment of advanced solid tumors.

The study is designed to assess the safety in activity of three once weekly doses of Aktiv 500, as a monotherapy in the salvage setting of disease.

And in combination with one of three FDA approved checkpoint inhibitor therapies and patients whose tumors failed to respond or progressed. Following initial response with prior checkpoint inhibitor therapy.

Patients who are clinically stable following the first cycle that HTI 500 treatment are eligible to receive the second treatment cycle of three additional once weekly doses of S&P 500 for a total of up to six doses at each dose level.

Importantly, the dose escalation stage of the of the Phase. One study of 5500 is designed to assess safety and Tolerability.

Scott Walshco: Importantly, the dose escalation stage of the phase one study of FT500 is designed to assess safety and tolerability. The FT500 clinical trial is the first ever clinical trial in the United States of an ITF-derived cell product. Additionally, it is one of the first ever clinical trials to systematically evaluate a novel treatment paradigm for cell therapy, where multiple doses are administered over multiple cycles. Finally, FT500 is the first universal off-the-shelf and K-cell product to be combined with checkpoint inhibitor therapy. To best promote a first principles assessment of safety and tolerability of FT500, patients in dose escalation are to receive a mild outpatient lymphoconditioning regimen prior to the first treatment cycle only and no cytokine support. A key objective for the dose escalation stage is to complete a robust assessment of the patient's immunological response to FT500, including, first and foremost, measuring endogenous immune cell reconstitution and 2. Cytokine activity, including evidence of cytokine release syndrome, neurotoxicity, and GVHD 3.

The S&P 500 clinical trial is the first ever clinical trial in the United States of an IP us drive cell product.

Additionally, it is one of the first of all clinical trials to systematically evaluate a novel treatment paradigm for cell therapy.

Or multiple doses are administered over multiple cycles.

Finally FC 500 is the first universal off the shelf NK cell product to be combined with checkpoint inhibitor therapy.

To best promote a first principles assessment of safety and Tolerability of HTI 500 patients in dose escalation are to receive a mild outpatient lymphoma conditioning regimen prior to the first treatment cycle only.

No cytokine support.

A key objective for the dose escalation stage is to complete a robust assessment of the patients immunological response to ft 500, including.

Number one measuring and dodging us immune cell reconstitution and activation, including CD eight cytotoxic T cells and T regulatory cells.

Two cytokine activity, including evidence of cytokine release syndrome, neuro toxicity, and Gvhd and three the occurrence of untied sell immunogenicity, including evidence of rejection mediated by by endogenous b cells and T cells.

Scott Walshco: The occurrence of anti-cell immunogenicity, including evidence of rejection mediated by endogenous B-cells and T-cells. We continue to be pleased with the progress and preliminary indications of clinical safety and tolerability we have observed to date in the dose-escalating stage of the FT500 Phase I clinical trial. In the monotherapy arm of the study, three patients have been treated at 100 million cells per dose, and five patients have been treated at 300 million cells per dose, with no reported dose-limiting toxicities or FT500-related serious adverse events. Additionally, in the combination arm of the study in patients that have failed prior checkpoint inhibitor therapy, three patients have been treated at 100 million cells per dose in combination with checkpoint inhibitor therapy with no reported dose-limiting toxicities or FT500-related serious adverse events.

We continue to be pleased with the progress and preliminary indications of clinical safety and Tolerability. We have observed to date in the dose escalating stage of the 5500 phase one clinical trial.

In the monotherapy arm of the study three patients have been treated at 100 million cells per dose and five patients have been treated at 300 million cells per dose with no reported dose limiting toxicities or EFT HTI 500 related serious adverse events. Additionally, in the combination arm of the study in patients.

That has failed prior checkpoint inhibitor therapy three patients have been treated at 100 million cells per dose in combination with checkpoint inhibitor therapy with no reported dose limiting toxicities or EFT HTI 500 related serious adverse events.

Enrollment in the dose escalating stage.

Scott Walshco: Enrollment in the Dose Escalating Stage of the FT500 Phase I clinical trial is currently ongoing at 300 million cells per dose in the combination arm of the study. Subject to establishing safety at this dose level, we plan to initiate dose expansion in the combination arm of the study only, with an amended clinical protocol that is specifically designed to promote FT500 anti-tumor activity. These modifications include enriching for tumors with partial or complete loss of MHC class 1 expression based on pretreatment biopsy, adding cytokine support to induce NK cell activity, and selecting cancers that are most amenable to NK cell infiltration.

Of the FTC 500 phase one clinical trial is currently ongoing at 300 million cells per dose in the combination arm of the study.

Subject to establishing safety at this dose level, we plan to initiate dose expansion.

In the combination arm of the study only.

With an amended clinical protocol that is specifically designed to promote F. T 500 anti tumor activity. These modifications include enriching for tumors with partial or complete loss of MHC class one expression based on pretreatment biopsies.

Adding cytokine support to induce NK cell activity and selecting cancers that are most amenable NK cell infiltration.

Scott Walshco: We look forward to sharing our initial clinical insights into our first in-human clinical experience with FT500 and our plans for the design of the dose expansion stage of the FT500 clinical trial at the upcoming 61st American Society of Hematology annual meeting. As we look toward the end of 2019, we are pleased that our IPS-derived self-based cancer immunotherapy pipeline will be featured at both the 34th Annual Meeting of the Society for Immunotherapy of Cancer, as well as the 61st Annual ASH Meeting. At CITSE, during the Sunday plenary session entitled Innovations in Cellular Therapy for Therapeutically Targeting Advanced Malignancies, Dr. Jeff Miller of the University of Minnesota is scheduled to showcase the company's off-the-shelf IPS-derived NK cell platform and present preclinical data demonstrating the cytotoxic function of FT500 as compared to donor-derived NK cells, and the synergistic anti-tumor activity of FT500 in combination with checkpoint inhibitor therapy.

We look forward to sharing our initial clinical insights into our first in human clinical experience with up to 500.

And our plans for the design of the dose expansion stage of the F. T 500 clinical trial at the upcoming 60, Onest American Society Hematology annual meeting.

As we look toward the end of 2019, we're pleased that our IP us derived cell based cancer immunotherapy pipeline will be featured at both the 34th annual meeting of the Sidey for immunotherapy of cancer as well as the 60 Onest annual Ash meeting.

At city during the Sunday plenary session entitled innovations in cellular therapy for therapeutically targeting advanced malignancies, Dr., Jeff Miller of the University of Minnesota is scheduled to showcase the companys off the shelf IP us derived NK cell platform and presented preclinical data demonstrating the.

Cytotoxic function of HTI 500, as compared to donor derived NK cells and the synergistic anti tumor activity of that HTI 500 in combination with checkpoint inhibitor therapy.

Scott Walshco: Additionally, I'm pleased to announce that we had six abstracts accepted for presentation at ASH, which will be unveiled tomorrow morning, and that we will be hosting our fourth annual ASH Investor event on Friday evening, where we will be joined by esteemed guests, including Dr. Miller of the University of Minnesota, a pioneer of adoptive NK cell therapy and our collaborator in developing IPS-derived NK cell cancer immunotherapies. Dr. Eric Smith of Memorial Sloan Kettering Cancer Center, an expert in cellular immunotherapy for multiple myeloma, and Dr. Michelle Satterlein of Memorial Sloan Kettering Cancer Center, a pioneer of CAR T-cell therapy, and our collaborator in developing off-the-shelf, IPS-derived T-cell immunotherapies, including FT8, our first IPS-derived CAR T-cell product targeting Finally, I want to recognize recent accomplishments of the Protoimmune Clinical Trial and Manufacturing. In October, we completed patient enrollment and treated the 80th patient in the randomized, controlled, and double-blinded Phase 2 PROTECT study of prognosis.

Additionally, I'm pleased to announce that we had six abstracts accepted for presentation at Ash, which will be unveil tomorrow morning.

And that we will be hosting our fourth annual ash investor event on Friday evening.

Where we will be joined by a steam guests, including Dr. Miller of the University of Minnesota, a pioneer of adoptive NK cell therapy, and our collaborator and developing IP us derived NK cell cancer Immunotherapies.

Dr., Eric Smith of Memorial Sloan Kettering Cancer Center, an expert in cellular immunotherapy for multiple myeloma.

And Dr. Michel satellite of Memorial Sloan Kettering Cancer Center, a pioneer of car T cell therapy, and our collaborator and developing off the shelf IP EPS derive T cell immune therapies, including FDA 19, our first IP has derived car T cell product targeting b cell malignancies.

Finally, I want to recognize recent accomplishments of the proto immune clinical trial and manufacturing team.

In October we completed patient enrollment and treat the 80 patient in the randomized controlled and double blinded phase to protect study of production.

Scott Walshco: Proteimmune is the company's first-in-class allogeneic hematopoietic cell product candidate for the prevention of acute graft-versus-host disease in patients undergoing hematopoietic cell transplantation for the treatment of hematologic malignancy. GVHD is the leading cause of early morbidity and mortality following allogeneic transplantation, and there are currently no therapies for the prevention The completion of patient enrollment is a notable operational achievement for the company, and we look forward to seeing the data from this blinded study in 2020. Turning to our financial results, revenue was $2.4 million for the third quarter of 2019, compared to $1 million for the same period last year.

Permian is the Companys first in class Allogeneic hematopoietic cell product candidate for the prevention of acute graft versus host disease in patients undergoing hematopoietic cell transplantation for the treatment of hematologic malignancies.

Gvhd is the leading cause of early morbidity and mortality following allogeneic transplant and there are currently no therapies for the prevention of acute gvhd approved by the FDA.

The completion of patient enrollment is a notable operational achievement for the company and we look forward to seeing the data from this blinded study in 2020.

Turning to our financial results revenue was $2.4 million for the third quarter of 2019 compared to $1 million for the same period last year revenue in the current quarter was derived from the company's IP FC derived car T cell collaboration with Ono pharmaceutical.

Scott Walshco: Revenue in the current quarter was derived from the company's IPSC-derived CAR T-cell collaboration with Ono Pharmaceutical. Research and development expenses for the third quarter of 2019 were $23.2 million compared to $13.6 million for the same period last year. The increase in our R&D expenses was attributable primarily to an increase in employee compensation, including stock-based compensation associated with growth in headcount; internal and third-party expenses associated with the clinical development and manufacture of the company's product candidates; and expenses associated with conducting research activities under our collaboration with Ono Pharmaceuticals. G&A expenses for the third quarter of 2019 were $6.3 million, compared to $4.1 million for the same period last year. The increase in our G&A expenses was attributable primarily to an increase in employee compensation, including share-based compensation.

Research and development expenses for the third quarter of 2019 or $23.2 million compared to $13.6 million for the same period last year.

The increase in our R&D expenses was attributable primarily to an increase in employee compensation, including stock based compensation associated with growth in head count.

Internal and third party expenses associated with a clinical development and manufacture of the company's product candidates and expenses associated with conduct of research activities under our collaboration with Ono pharmaceutical.

Gionee expenses for the third quarter of 2019 were $6.3 million compared to $4.1 million for the same period last year. The increase in our Gina expenses was attributable primarily to an increase in employee compensation, including share based compensation.

Scott Walshco: Total operating expenses were $25 million for the third quarter of 2019, net of non-cash stock-based compensation expense of approximately $4.6 million. In September, the company completed a $173 million common stock offering. Including net proceeds from the offering, the company ended the third quarter of 2019 with $303 million of cash, cash equivalents, and short-term investments. Common Stock Outstanding was 75.4 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.

Total operating expenses were $25 million for the third quarter 2019, net of noncash stock based compensation expense of approximately $4.6 million.

In September the company completed a 100 $173 million common stock offering.

Including net proceeds from the offering the company ended the third quarter of 2019 with $303 million of cash cash equivalents in short term investments.

Common stock outstanding was 75.4 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.

Scott Walshco: I continue to be pleased with the company's operational progress, its expanding leader position, and our pursuit of bringing disruptive cellular immunotherapies to patients with cancer, and we are well positioned to generate decisive clinical data across multiple product candidates from our IPSC product platform. And with that, I'll open the call to questions. Please, gentlemen, to ask a question, you will need to press the start and the 1 key on your touch-tone telephone.

I continue to be pleased with the company's operational progress and expanding leadership position and our pursuit of bringing disruptive cellular immunotherapies to patients with cancer and we are well positioned to generate decisive clinical data across multiple product candidates from our IPO C product platform.

And with that ill open the call up to questions.

Ladies and gentlemen to ask question you will need to press the star agenda, one key touched on telephone.

Scott Walshco: To withdraw your question, please press the pound, Please stand by while we compile the Q&A. And our first question coming from the line of Alethea Young. Yolana So, Hey guys, thanks for taking my questions and congrats as we move toward closer to kind of a readout, your ASH, I guess, to one, you know, we saw the release from Allogene going after IPSCs today with Notch Therapeutics, so maybe just talk about points of differentiation that you perceive in that technology and then, you know, also you are starting to add a notable amount of patients in FT500, so I just want you to talk about what it means from the safety that you're seeing and the implications around re-dosing and how we should make a read to the platform.

Your question please press the pound.

Please standby compile the keanu roster.

And our first question coming from the line of lead.

From Cantor Fitzgerald Your line is open.

Hey, guys. Thanks for taking my questions and congrats as we move toward closer to kind of it read out.

Yes, I guess too.

We saw the release from Al Jane I am going after IPO assays today with non sterile. So maybe just talk about plant that differentiation that you perceive and that technology and then it also you are starting to add a notable amount of patients NFC 500 sounds like it's mainly from the safety that you're seeing and the implications around re dosing and how we should make.

The read to the platform. Thanks.

Sure. So I'll talk about Allen gene and sort of there.

Initiative in IP Etsys Wayne should feel free to talk about your initial results were seeing with up to 500, which we can are going to talk much more about at ash.

Scott Walshco: Sure. So, I'll talk about Allogene and their sort of initiative in IPSCs. Wayne should feel free to talk about, you know, the initial results we're seeing with FT500, which we are going to talk much more about at ASH. The group that Allogene did the collaboration with is led by an investigator, Juan Carlos Fucher. And so, we are very familiar with Dr. Fucher. We've had conversations with Dr. Fucher, quite frankly, dating back to probably five years. And we're very familiar with his technology. Our understanding of his technology is that it primarily relates to the maturation of T-Cells and Maturing T-Cells to Specific Phenotypes. In all my conversations with Juan Carlos, interestingly enough, I have never viewed him as someone who is an expert in IPS cell technology.

The group that allergy and did the collaboration with is led by an investigator Juan Carlos few curve.

And so we are very familiar with Dr. fluker, we've had conversations with Dr. fluker quite frankly dating back for probably five years and were very familiar with this technology.

Hi.

Our read of his technology is that his technology, primarily relates to maturation of T cells and maturing T cells to specific phenotypes I mean in all my conversations with one Carlos Interestingly enough have never viewed him as someone who is an X.

For an IPO cell technology quite frankly, so I think the technology is interesting as it relates to how you might mature us sell.

Scott Walshco: So, I think the technology is interesting as it relates to how you might mature a cell to a specific T cell phenotype. But I did not, and I don't think Juan Carlos necessarily views himself as an expert in IPS cell technology. I would say we've looked at the technology that is being used by that group, and we are very comfortable with the technology we've developed under our Memorial Sloan-Kettering collaboration, the phenotype of the T cells we're generating, and we plan to highlight some very significant in vivo data at ASH. Bob, if you have anything to add to that, No, that's exactly right.

To a specific T cell phenotype.

But I did not and I don't think Juan Carlos necessarily views himself as an expert in IP cell technology I would say we've looked at that technology that is being used by that group and we are.

Very comfortable.

With the technology, we have developed under a memorial Sloan Kettering collaboration.

The phenotype of the T cells were generating and we plan to highlight some very significant in vivo data at ash.

I don't know bogs, you have anything to add to that no. That's exactly right. We've we've been talking to JC for quite some time as Scott mentioned and as technology is associated with ticket him out of places down that T cell lineage, specifically micro beat that have expecting ligands deal for and become which has been published a couple of years ago.

Scott Walshco: You know, we've been talking to JC for quite some time, as Scott mentioned, and his technology is associated with taking hematopoiesis down the T cell lineage, specifically microbeads that have expressing ligands, DL4, and VCAM, which has been published a couple years ago. He is amazing in T cell development, but when it comes to iPSC culture, I think, as Scott, seen by J.C.'s technology. And then with respect to FT500, I mean, I'll turn it over to Wayne, and he's obviously very closest to running the FT500 clinical study, and he can comment, you know, a little bit more on safety that we're seeing with respect to the multi-dose paradigm. But really, we're looking forward to unveiling, you know, a deeper dive on what we're seeing at our ASH Investor Event. Yeah.

He is amazing and T cell development, but when it comes I PSC culture, I think as Scott mentioned.

There is that yes, we're still thing we have a differentiated platform that Scott.

Seen by Jaycees technology.

And then with respect to 5500, I mean alternative I'll turn it over to Wayne I mean is obviously very closest to running the 5500 clinical study and he can comment on.

A little bit more on saved on safety and that we're seeing with respect to the multi dose paradigm, but really we're looking forward to on dialing a deeper dive on what we're seeing at our ash invest investor event.

But I can say about 5500 us as was a Scott mentioned.

Earlier that I think what are the key objectives of 5500 is demonstrating that safety and tolerability of giving multiple doses on demand of ft 500 patients that I think one important point to remember is that all of these F. 3500 doses are administered on an outpatient basis. So unlike.

Scott Walshco: What I can say about FT500 is, as Scott mentioned earlier, that I think one of the key objectives of FT500 is demonstrating the safety and tolerability of giving multiple doses on demand of FT500 to patients. And I think one important point to remember is that all of these FT500 doses are administered on an outpatient basis. So unlike some of the other autologous CAR-T products that require mandatory hospitalization for monitoring, we do not have such a requirement.

Some of the other autologous car T products that require mandatory hospitalization for monitoring we do not have such requirement.

And the patients that we have treated to date with 5500 have all tolerated you. The 5500 quite well really the there's been no dose limiting toxicities or any related serious adverse events as was mentioned before.

Scott Walshco: And, you know, the patients that we have treated to date with FT500 have all tolerated FT500 quite well. Really, there have been no dose-limiting toxicities or any related serious adverse events, as mentioned before. And really, primarily, reasons for not continuing to the full course of FT500 are really related to underlying disease rather than anything related to FT500. So it's still relatively early days, but we're very encouraged by what we've seen so far from a safety and tolerability perspective. Great, thank you. And our next question comes from the line of..., with Guggenheim Securities, Yelena Sobchak. Hey, this is Kelsey on behalf of Michael.

And really primarily reasons for not continuing to the full course of ft, 500 are really related to underlying disease.

Anything related to 500, so it's still relatively early days, but we're very encouraged by what we've seen so far from a safety and Tolerability perspective.

Great. Thank you.

And our next question coming from the line.

With Guggenheim Securities. Your line is open.

Hey, Mrs Kelcy on for Michael Thanks for taking our questions.

I guess kind of more bigger picture and now that you kind of keep adding increasingly more at its now are up to three kind of in the clinic I guess, how have you seen regulators respond to this increased complexity and do you see a ceiling for the number of edits that you could make to the sales. Thanks.

Scott Walshco: Thanks for taking our questions. I guess kind of a bigger picture, now that you kind of keep adding increasingly more edits, now we're up to three kind of in the clinic. I guess, how have you seen regulators respond to this increased complexity? And do you see a ceiling for the number of edits that you could make to these sales? Thanks.

Sure.

I'll touch lightly on this topic because it has to do with regulatory regulators view the editing I do think as we've talked about in the past I do think we have a significant advantage when it comes to gene editing.

Scott Walshco: Sure. I'll touch lightly on this topic because it has to do with regulators' views on editing. I do think, as we've talked about in the past, I do think we have a significant advantage when it comes to gene editing. And that is imparted upon us based on the specific nature of our platform where we're engineering iPS cells and selecting a specific clone where the engineered properties are locked in, and they are uniform just by the very nature of selecting a single clone. And so I think that is very unique.

And that is imparted.

Upon us based on the specific nature of our platform were were engineering IP Upsells and we're selecting a specific loan.

Where that and the engineered properties are locked in and they are uniform just by the very nature of selecting a single clung.

And so I think that is very unique I think in the world of patient derived cell therapy or donor derived cell therapy, where your engineering at a batch level.

Scott Walshco: I think in the world of patient-derived cell therapy or donor-derived cell therapy where you're engineering at a batch level, I believe, and our experience has been, at least pre-clinically, it is very challenging, to create homogeneous product and that there are significant off-target effects associated with batch engineering, especially when you're trying to do two, three, four, five edits. I mean, Dan can talk a little bit about the work we're doing under Ono collaboration right now, but we're certainly, you know, have not stopped at three. Certainly we've stopped there with FC596 in the clinic, but what we're doing under the Ono collaboration and the limits that we're seeing, I mean, we're thinking about for solid tumors ultimately that, you know, we are exploring right now four or five, six edits as part of a IPSC platform, again, where you have the benefit of one-time engineering, selecting a single clone, and fully characterizing the elements associated with that engineering event.

I believe in our experience has been at least Preclinically. It is very challenging to create homogeneous product and that there are significant off target effects associated with batch engineering, especially when you're trying to do to three.

345 edits.

Dan can talk a little bit about the work we're doing what under Ono collaboration right now, but we're certainly have not stopped at three certainly we'd stop there with FC five six in the clinic, but what we're doing under the Ono collaboration and the limits that we're seeing I mean, we're thinking about for solid tumors. Ultimately that we are exploring right now.

456 edits.

As part of a IP FC platform again, where you have the benefit of onetime engineering selecting a single clone and fully characterizing the elements associated with that engineering event, and then that translates all the way to the patient because ultimately the patient is receiving a homogeneous cell.

Our product and quite frankly that homogeneous cell product has been that exact product with those engineering features has been thoroughly pre clinically tested before seeing a patient and I think thats and that's I think a very that's another unique difference.

Scott Walshco: And then that translates all the way to the patient, because ultimately, the patient is receiving a homogeneous cell product, and quite frankly, that homogeneous cell product has been, that exact product with those engineering features has been thoroughly preclinically tested before seeing a patient, and I think that's another unique difference. We can do preclinical evaluation of all that editing and ensure that the patient is receiving that product. And that is very different than batch production.

We can do re clinical evaluation of all that editing.

And ensure that the patient is receiving that product and that is very different than batch engineering I'll turn it over to Danny provide more insight into these on collaboration.

Just a few thoughts here is we're really as I said their lead products now have three edits, it's really focused on dual targeting persistence and just sort of the function of the base.

Cards, including KSL as we then look towards.

Scott Walshco: And I'll turn it over to Dan to provide more insight into the collaboration. Just a few thoughts here: we're really, as you just said, our lead products now have three edits. It's really focused on dual targeting, you know, persistence, and just sort of the function of the base CAR-T and CAR-NK cell. As we then look towards solid tumors, there are whole new realms of opportunity to make these cells better, stronger, faster with respect to trafficking, infiltration into the tumor, overcoming the tumor microenvironment, and recruiting other immune cells into the tumor to turn cold tumors hot. So I think the future is really going to take the shape of how we are going to build on this current generation of basic products to overcome the challenge of solid tumors.

All the tumors, there's there's whole new realms of opportunity to make the sells better stronger faster with respected trafficking trafficking infiltration into the tumor overcoming the tumor microenvironment and recruiting other immune cells into the.

Tumor to turn cold tumors Hot so I think the future is really going to take the shape of how are we going to build on this current generation of based products.

To to overcome the challenge in solid tumors and I think as we sort of assessed the competitive landscape of what different platforms are capable of doing I think one of the unique strengths of our IP has called platform is the ability to generate these highly edited quotable I guess populations in performed extensive characterization to demonstrate.

All of the.

Rigorous copy number variation and translocations and things that can happen. These are just part of our standard QC process that we think is a unique path to getting to these really extraordinary processes and.

Scott Walshco: And I think as we sort of assess the competitive landscape of what different platforms are capable of doing, I think one of the unique strengths of our IPS clonal platform is the ability to generate these highly edited clonal IPS populations and perform extensive characterization to demonstrate all of the, you know, rigorous copy number variation and translocations and things that can happen. These are just part of our standard QC process that we think is a unique path to getting to these, you know, really extraordinary processes, and this is, you know, one of the things we're most proud about. Great, thanks for the color.

One of things were most proud about.

Great Thanks to the color.

Our next question coming from the line Ben.

Stifel. Your line is open.

Great. Thanks for the question.

Just two questions and and thank you for laying out so explicitly the T 500 updates at city National we can expect but can you provide maybe just a little bit more color as to whether any ft 516 data will be disclosed by their dr. Miller at Citi. Your by fate.

The company's I've been at Ash.

Sure so at Ft, sorry at Citi.

Can absolutely confirmed that Dr. Miller is not going to disclose clinical data around 55 16.

Scott Walshco: Our next question comes from the line of Ben Burnett, for Yolanda Salter. Good. Thanks for the question. Just two questions, and thank you for laying out so explicitly the FT500 updates at CITSE and ASH that we can expect, but can you please provide maybe just a little bit more color as to whether any FT516 data will be disclosed by either Dr. Miller at CITSE or by Fate at the company's event at ASH? Sure, so at FT, sorry, at CITSE, I can absolutely confirm that Dr. Miller is not going to disclose clinical data around FT-516. His presentation at CITSE is about FT500 and the preclinical data package around FT500, including the value of NK cells synergizing with checkpoint inhibitor therapy, which he has a publication that I think is currently in review around that. So he will be discussing that at CITSE. At the ASH conference, we do have an ASH event.

His presentation at city is around 5500, and the preclinical data package around 5500, including the value of NK cells Synergizing with checkpoint inhibitor therapy, which has a publication that I think is currently in review around that so he will be discussing that at Citi.

At the Ash conference, we do have an actual events or events, obviously I can't speak to what.

Abstracts will be unveil tomorrow, but we will give an update certainly on up to 500 I think it's a little too early for us to say definitively whether ft 516 will be part of the clinical update or not but certainly we're very pleased with the fact that weve dose the first two patients.

The first obviously being in lymphoma arm in combination with her toxin and.

The second being in AML.

Okay got it that's helpful and.

Maybe if I could just ask beyond ash and ended this year sort of what sort of the cadence of clinical updates for 55, 16, and and I don't know if it's early but also ft. Fiveninety six so we can expect.

Scott Walshco: Obviously, I can't speak to what abstracts will be unveiled tomorrow, but we will give an update, certainly on FT500. I think it's a little too early for us to say definitively whether FT516 will be part of the clinical update or not. But certainly, we're very pleased with the fact that we've dosed the first two patients, the first obviously being in the lymphoma arm in combination with rituxan, and the second being in AR. Okay, I got it.

Yes, I think I think we'll be happy to talk talk more about this at ash.

Okay, Okay, and maybe if I could just squeeze one more on pressure then.

If I recall, there were some discussion or other potential to use a day 100 endpoint versus maybe waiting for days mature and look at a longer I think we talked about a one year end point, which could potentially informal on survival. I guess can you just remind us sort of current thinking and wondering when we can expect pardon me and try to read out in sort of what the endpoints are that.

That you're looking at.

Yeah. The primary endpoint of the study you are correct as a day 100 endpoint its cumulative incidence of grade two through four Gvhd at day 100.

Scott Walshco: That's helpful. And maybe if I could just ask, beyond ASH and into this year, sort of, what's the cadence of clinical updates for FT-516 and, I don't know if it's too early, but also for FT-596 that we can expect. Yeah, I think we'll be happy to talk more about this at ASH. Okay, okay.

We are finalizing the statistical plan right now with respect to the primary endpoint and we are looking very closely at also including a key secondary endpoint, which is a composite around freedom from chronic gvhd relapse and death.

At day 365, and we've been we are going to discuss this more at ash with our key investigators in the in the protect study, but that key composite endpoint as we've thought about it and gotten feedback is important to at least consider that as a potential secondary end point given.

Scott Walshco: And maybe if I could just squeeze one more on protamine, then. You know, if I recall, there was some discussion around the potential to use a day 100 endpoint versus maybe waiting for data to mature and look at a longer, I think we talked about a one-year endpoint, which could potentially inform on survival. I guess, can you just remind us sort of current thinking and when we can expect the protamine trial to read out and sort of what the endpoints are that you're looking at? Yeah, the primary endpoint of the study, you are correct, is a day 100 endpoint. It's cumulative incidence of grade 2 through 4 GVHD at day 100.

And it does represent essentially that the totality of the outcome of transplant.

Okay perfect. Thank you.

Our next question coming from the line.

Oppenheimer Your line is open.

Hey, guys. Thanks for taking my questions.

Definitely lot of progress lot to digest.

A quick clarification on FC Fivenine Sixs stays on is it only a single patient that will be enrolled in the monotherapy cohort.

And also on that phase one isn't all comers by design or will you be excluding patients who are cdnineteen negative.

Sure I'll, let Wayne answer those questions, Yes, RFP fivenine fix it will initially start as a monotherapy cohort by will directly transition into an escalation that focuses on the combination of 50 596.

Scott Walshco: We are finalizing the statistical plan right now with respect to the primary endpoint, and we are looking very closely at also including a key secondary endpoint, which is a composite around freedom from chronic GVHD, relapse, and death at day 365. And we've been, and we are going to discuss this more at ASH with our key investigators in the PROTECT study. But that key composite endpoint, as we've thought about it and gotten feedback, it is important to at least consider that as a potential secondary endpoint, given it does represent essentially the totality of the outcome of transplantation. Okay, perfect. Thank you. Our next question comes from the line of Matt Biegler with Oppenheimer, your line. Hey guys, thanks for taking our questions.

With the anti Cdtwenty monoclonal antibodies, specifically, we are tougher have so that initial cohort as just the three patient cohort and adherence to 3.3 dose escalation principle. So minimum three patients will need to be enrolled in that monotherapy cohort before being tested at that same dose.

Those but in combination with were tux map and then dose escalation will proceed from there as far as the types of patients to be enrolled.

We it's generally quite broad across multiple sub types of non hodgkin's lymphoma with the goal of of getting to the maximum tolerated dose or maximum assess dose as quickly as possible and then at the point of dose expansion.

Scott Walshco: Definitely a lot of progress, a lot to digest. A quick clarification on FT596's phase one. Is it only a single patient that will be enrolled in the monotherapy cohort? And also, in that phase one, is it all covered by design, or will you be excluding patients who are CD19 negative? Sure, I'll let Wayne answer those questions.

And we have the optionality of enrolling specific cohort.

Based on histology and other baseline characteristics, where we would then look at the overall safety tolerability and anti tumor activity in greater depth.

Got it that's helpful. On and then I was just wondering if we should expect any updated data from the NK 100 program I mean, I do realize that these programs have been discontinued in the focuses on the IPO thing I pfcs going forward.

Scott Walshco: Yeah, so for FT-596, it will initially start as a monotherapy cohort, but it will directly transition into an escalation that focuses on the combination of FT-596 with anti-CD20 monoclonal antibodies, specifically Rituximab. So that initial cohort is just a three-patient cohort in adherence to three plus three dose escalation principles. So, at least three patients will need to be enrolled in that monotherapy cohort before being tested at that same dose but in combination with Rituximab, and then dose escalation will proceed from there.

Yes, I think on we're having discussions right now with the investigators that that are involved in that study with respect to whether they would like to publish that data presented data at various conferences.

We're very open to that and I think actually at sea, Jeff May provide a little bit of update on the ovarian study quite frankly I've seen a draft of his presentation. There is a little bit of an update on the of ovarian study with NK 100.

Scott Walshco: As far as the types of patients to be enrolled, you know, it's generally quite broad across multiple subtypes of non-Hodgkin's lymphoma, you know, with the goal of getting to the maximum tolerated dose or maximum assessed dose as quickly as possible. And then at the point of dose expansion, we have the optionality of enrolling specific cohorts based on histology and other baseline characteristics, where we would then look at the overall safety, tolerability, and anti-tumor activity in greater depth. I got it.

Okay. Thanks, guys.

Sure.

Our next question coming from the line of men.

Your line is open.

Hi, Thank you.

Just a question on slide nine six.

Obviously, then it gets added 500 516 in terms of laying out.

What you view to me the comparable.

And your efficacy targets, I guess or ER Bogeys, how do you think about that.

Nine six perspective, I know there is not obviously.

Scott Walshco: That's helpful. And then I was just wondering if we should expect any updated data from the NK-100 programs. I mean, I do realize that these programs and the focus is on the IPSC going forward. Yeah, I think, you know, we are having discussions right now with the investigators that are involved in that study with respect to whether they would like to publish that data or present data at various conferences. You know, we're very open to that, and I think actually at CITSE, Jeff may provide a little bit of an update on the ovarian study. Quite frankly, I've seen a draft of his presentation.

The comparisons that are already out there.

I wanted to MD Anderson slightly different but just kind of thinking about what you're looking for in both arms and our sponsor and durability in theory for that went to that.

Therapeutic.

So for so far ft 596.

Because it has many of the features that we think our desirable to maximize efficacy against lymphoma.

And based on what information has been that it's been released so far regarding NK cell based therapies with a cdnineteen directed car, but we're expecting to see with ft. Fivenine six quite frankly is the level of efficacy.

Scott Walshco: There's a little bit of an update on the ovarian study with NK100. Okay, thanks guys. Our next question comes from the line of Amanda Murphy with VTIG. Hi, thank you.

Matt approaches the level of that's seen with other adoptive cell therapies.

But potentially with a safety profile that is quite manageable in the sense that minimal cytokine release syndrome minimal neurotoxicity.

Scott Walshco: Just a question on 596. You know, you've obviously done a good job with 50516 in terms of laying out, what you view to be the comparable, you know, efficacy targets, I guess, or sort of the bogeys. How do you think about that from a 596 perspective? I know there's not, you know, obviously easy comparisons that are already out there, other than maybe MD Anderson, slightly different, but just kind of thinking about what you're looking for in both arms and response and durability in theory for that one, for that therapeutics. So for FT-596, because it has many of the features that we think are desirable to maximize efficacy against lymphoma, and based on what information that has been released so far regarding NK cell-based therapies with a CD19-directed CAR, what we're expecting to see with FT-596, quite frankly, is a level of efficacy that, you know, approaches the level that's seen with other adoptive cell therapies, but potentially with a safety profile, you know, that is quite manageable in the sense that minimal cytokine release syndrome, minimal neurotoxicity, you know, in totality, which still enables us, despite the addition of these genetic engineering elements, to administer FT-596 on an outpatient basis.

In totality of which still enables us. Despite the addition of use genetic engineering element to administer ft fivenine fix on an outpatient basis and certainly.

Because of the flexibility with respect to multiple dosing and even flexibility with dose and schedule. One would hope that we would not only be able to achieve deep responses at a meaningful level of.

Frequency, but also have these responses be durable.

Do you have the apps into tweak the lymphodepletion as well or is that pretty much set at the plant.

If you want asset I mean, when can answer I mean, basically are I think our view is that.

What we've seen him and the conversations we've had the with the FDA ft is very amenable to protocol changes.

That are based on clinical data.

Yes that.

So certainly given this is still a relatively new area.

I think that the limbo conditioning regimen that we specified for F 35.6, I would consider as a starting point.

As we get more data regarding the persistence of empty fivenine six maybe in data around the pharmacokinetics of 55 dissect the safety efficacy, so and so forth, we'll have the opportunity to look into the possibility of modifying lymphoma conditioning.

Scott Walshco: And certainly, because of the flexibility with respect to multiple dosing and even flexibility with dose and schedule, one would hope that we would not only be able to achieve deep responses at a meaningful level of frequency but also have these responses be durable. Do you have the option to tweak the lymphodipletion as well, or is that pretty much set at this point? Wayne can answer that.

Even if it means modifying liberal conditioning with a subsequent cycle compared to the first there are lot of different variables that one can consider but we would need to generate that data before we wouldn't make informed decision on that.

Second sneaking, one about sort of longer term cost and I guess in the answer maybe just wait for asked so thats fair, but just curious obviously made a lot of progress on the team saw back on site as well.

Scott Walshco: Basically, I think our view is that, based on what we've seen and the conversations we've had with the FDA, the FDA is very amenable to protocol changes that are based on clinical data. Yeah, I think that, you know, certainly given that this is still a relatively new area, I think that the lymphoconditioning regimen that we specified for FT-596 could be considered as a starting point. You know, as we get more data regarding the persistence of FT-596, maybe, you know, data around the pharmacokinetics of FT-596, the safety, the efficacy, so on and so forth, we'll have the opportunity to look into the possibility of modifying lymphoconditioning, you know, even if it means modifying lymphoconditioning with a subsequent cycle compared to the first. There are a lot of I can just sneak in one about sort of a longer-term question, I guess, and the answer may be just wait for Ash, so that's fair.

When you think going forward from here.

How are you thinking that prior to the extent of the pipeline between.

That's in the energy products, you talked about PCB cars to be 30, it not got et cetera. These are the at T. T cell back then.

Candidate.

So from my perspective.

We are doing both.

And we're completely committed to doing both.

There may be we've talked about this a little the past there may be situations, where T cells. We think T cells are particularly advantaged there may be tumor types for instance, we've talked about the solid tumor types, where MHC class. One has been down regulated where T cells are clearly not advantaged and NK cells might be advantaged and.

I have said this publicly before it will not surprise me within.

Well, let's just give a two years if a cell therapy as given that is comprised of both NK cells in T cells.

I could just simply not at that I can simply add.

In terms of prioritization of where to persuade individual products I think there will be largely dictated by what we see in terms of the clinical data that defines the risk benefit profile for these products and then matching them with the into what the individual disease, because as as many of US no lymphomas, a very heterogeneous disease.

Scott Walshco: But I just was curious, you obviously made a lot of progress on the T-cell backbone side as well. When you think going forward from here, how are you thinking about prioritizing the pipeline between some of the NQ products you talked about, you know, BCMA CAR, CD38 knockout, etc., vis-a-vis a T-cell backbone candidate? So from my perspective, we're doing both, and we're completely committed to doing both. There may be, we talked about this a little in the past, there may be situations where T-cells are particularly advantaged. There may be tumor types, for instance, we've talked about the solid tumor types where MHC class one has been downregulated, where T-cells are clearly not advantaged, and NK cells might be advantaged. And I have said this publicly before; it will not surprise me within, well, let's just give it two years.

Yes.

And what works what works really well in one indication may not necessarily work well in another indication.

That makes sense. Thank you.

Our next question coming from your line of foreign Amanda.

Jefferies. Your line is open.

Yes, hi, guys. Thanks for taking my questions.

Scott on Fiveninety, six what criteria would trigger re dosing of patients in that trial and I guess how are you.

Defining moderate Lymphodepletion, if you could just for the characterize that a bit more.

Sure I mean, we could touch on that so I mean actually I'll, let Bob both Bob in Wayne touch on this.

One of the things with that is very unique to 50 596 as Weve discussed it has three antitumor functionalities embedded into it one of them as the IL 15 receptor fusion I'll, let Bob talk about some of the preclinical data we've seen with that I'll 15 receptor fusion, which has led us on certainly to the conclusion that we are looking.

Scott Walshco: If a cell therapy is given that is comprised of both NK cells, I could simply add that, you know, I could simply add that in terms of prioritization of where to place individual products, I think it will be largely dictated by what we see in terms of the clinical data that defines the risk-benefit profile for these products and then matching them with the individual disease because, as many of us know, lymphoma is a very heterogeneous disease and, you know, what works really well in one indication may not That makes sense.

And only giving one dose per cycle based on what we've seen Preclinically and then I'll, let Wayne talk about the conditioning regimen, specifically that we're starting out for 50, 596, which I think you'll be very familiar with its a condition regimen that is used quite frankly by multiple groups in the car T cell space that are better conditions.

Scott Walshco: Thank you. Our next question comes from the line of Byron Amin with Jeffrey C. Alanisop. Yeah, hi guys, thanks for taking my questions.

And not depleting.

Yes, So Scott was mentioning that these modalities our tailor made for NK cell expansion and so for example, you take Io 50 receptor fusion that brings and not just fluctuation, but also survival and growth. So these cells are autonomous they can be cultured and the manufacturing process without the need for aisle to and how 15.

Scott Walshco: Scott, on 596, what criteria would trigger redosing of patients in that trial? And I guess, how are you defining moderate lymphodepletion? If you could just further characterize that a bit more? Sure, I mean, we can touch on that. So, I mean, actually, I'll let Bob, both Bob and Wayne touch on this.

That lack of.

Independence of cytokine support continues into the Nvvault models, we have and so we're very confident that the cells will persist.

Scott Walshco: You know, one of the things that is very unique to FT596, as we've discussed, it has three antitumor functionalities embedded into it. One of them is the IL-15 receptor fusion. I'll let Bob talk about some of the preclinical data we've seen with that IL-15 receptor fusion, which has led us, certainly to the conclusion that we are looking at only giving one dose per cycle, based on what we've seen preclinically. And then I'll let Wayne talk about the conditioning regimen, specifically, that we're starting out for FT596, which I think you'll be very familiar with. It's a conditioning regimen that is used, quite frankly, by multiple groups in the CAR T cell space that are conditioning and not.

As second triggering mechanism thats going to give details persistence and antigen mediated expansion is that card has been calibrated for and K biology, that's been highlighted by Scott in previous discussions and so the combination of these two modalities really gives the cells at boost where.

Onetime dose will be triggering enough of the activation and expansion of the cells to have it and effective clinical response.

And then add to the F 35006 clinical trial with specifically with respect to the lymphoma conditioning. It's essentially the same limbo conditioning regimen thats used for the car T. Specifically three consecutive days of Fludarabine and cyclophosphamide with the Fludarabine goes of being 30 milligrams per meter squared per dose and cyclophilin.

So my being 500 milligrams per meter square per dose.

You know importantly, what the F 30, 596 phase one is currently written with a single administration of Ft, 596, and then and then dose escalating based on that but you know in line with all of the other products. Our intention on goal is to get to a point, where we can give.

Scott Walshco: Yes, as Scott was mentioning, these modalities are tailor-made for NK cell expansion. And so, for example, you take the IL-15 receptor fusion, that brings about not just proliferation, but also survival and growth. So these cells are autonomous. They can be cultured in the manufacturing process without the need for IL-2 and IL-15.

Multiple doses of multiple cycles of 50 596, so even in the protocol is currently constructed as Scott mentioned.

Is the opportunity to give an additional cycle of ft fivenine six contingent on patients being clinically stable to receive a dose and that includes.

Scott Walshco: That independence of cytokine support continues into the in vivo models we have. And so we're very confident that the cells will persist. A second triggering mechanism that's going to give these cells persistence and antigen-mediated expansion is the CAR that's been calibrated for NK biology that's been highlighted by Scott in previous discussions. And so the combination of these two modalities really gives the cells a boost where one time dose will be triggering enough of the activation and expansion of the cells to have an effective clinical response. And then as to the FT-596 clinical trial, specifically with respect to the lymphoconditioning, it's essentially the same lymphoconditioning regimen that's used for the CAR-T, specifically three consecutive days of fludarabine and cyclophosphamide, with the fludarabine dose of being 30 milligrams per meter squared per dose, and cyclophosphamide being 500 milligrams per meter squared per dose.

Sufficient recovery from any treatment emergent adverse events following cycle, one and then any evidence of clinical improvement either clinically or radio graphically.

And then as Scott mentioned.

Once that data packages reviewed with FDA than patients potentially could get another cycle of 50 596, ultimately once we have sufficient data from several patients and have that discussion with FDA. The intention is that we would amend the ft Fivenine six phase one study.

Such that every patient coming on would have the opportunity to receive multiple cycles of ft, fivenine six without having to going through a data review on an individual patient by patient basis with the FDA.

Scott Walshco: Importantly, with FT-596 Phase I, it's currently written with a single administration of FT-596 and then dose escalating based on that. But, in line with all of the other products, our intention and goal is to get to a point where we can give multiple cycles of FT-596. So even in the protocol that's currently constructed, as Scott mentioned, there is the opportunity to give an additional cycle of FT-596 contingent on patients being clinically stable to receive a dose, and that includes sufficient recovery from any treatment or emergent adverse events following cycle one, and then any evidence of clinical improvement either clinically or radiographically. And then, as Scott mentioned, once that data package is reviewed with FDA, then patients could potentially get another cycle of FT-596.

So just on the FDA.

Review, how many patients.

With that fee a need before they're comfortable comfortable in approving an amendment to the protocol.

Have they disclose what that number is.

We don't know what that number is they have not disclose that number to us I do not believe.

It is.

A significant number of patients I think the FDA was asking us to.

As I have said before I mean this this is a first for cell therapy forget about IPO sees as a cell therapy that has three anti tumor modalities engineered into it and so I think the FDA is appropriately asking us to demonstrate a little bit of safety before launching into a treatment paradigm, which is all.

So novel, giving multiple cycles of therapy.

That's fair and I've got a couple of follow ups on.

For the other programs. So on 500, Scott you mentioned that.

Scott Walshco: Ultimately, once we have sufficient data from, you know, at least several patients and have that discussion with FDA, the intention is that we would amend the FT-596 Phase 1 study such that every patient coming on would have the opportunity to receive multiple cycles of FT-596 without having to go through a data review on an individual patient-by-patient basis with the FDA. So just on the FDA patient review, how many patients would FDA need before they're comfortable with approving an amendment to the protocol? Have they disclosed what that number is? We don't know what that number is. They've not disclosed that number to us.

You could potentially be enriching for tumors with partial or complete loss, if I may see one expression as well as and rushing for cancers with NK cell for infiltration and filtration. So for both of these parameters, how well to the quarterly in terms of.

Let's say long or renal cancer.

Yes, so I think on.

There's a high correlation with alone.

So I think about 40% of patients, 30% to 40% of patients that progress or fail on checkpoint inhibitor therapy.

If you look at the tumor the actual tumor that the mechanism of resistance.

Appears to be associated with significant down regulation, and then a C class one expression.

Scott Walshco: I do not believe it is a significant number of patients. I think the FDA was asking us to, you know, as I have said before, this is a first for cell therapy. Forget about IPSCs.

Additionally, when you administer NK cells systemically, they absolutely traffic through the long.

So based on when you look at.

Scott Walshco: This is a cell therapy that has three anti-tumor modalities engineered into it. And so I think the FDA is appropriately asking us to demonstrate a little bit of safety before launching into a treatment paradigm, which is also novel, giving multiple cycles of therapy. That's fair.

Significant in areas of resistance areas of resistance that are associated with a loss of MHC class won and potential for NK cells to traffic and infill trade.

Lung is rises to the top of the list.

Got it and then I guess on you also mentioned that you may have meant for cytokine support so.

Scott Walshco: And I've got a couple of follow-ups on the other programs. So, on 500, Scott, you mentioned that you could potentially be enriching for tumors with partial or complete loss of MHC1 expression, as well as enriching for cancers with NK cell infiltration. So, for both of these parameters, how well do they correlate in terms of, you know, let's say lung or renal cancer? Yeah, so I think, um... There's a high correlation with the lung.

Are you thinking about.

Ill administering I'll too.

After dosing B cells, yes, yes, I mean, that's historically what has been done with donor derived NK cell therapy and I believe it's also done with.

A particular til therapy that is everyone has sort of people's attention right now I'll twos, commonly given with doses and so when we think about amending the protocol to now promote NK cell.

Scott Walshco: So I think about 40% of patients, 30% to 40% of patients that progress or fail on checkpoint inhibitor therapy. If you look at the tumor, the actual tumor, the mechanism of resistance appears to be associated with significant downregulation of MHC class one expression. Additionally, when you administer NK cells systemically, they absolutely travel through the lung. So, based on when you look at, you know, significant areas of resistance, areas of resistance that are associated with a loss of MHC class 1 and the potential for NK cells to travel and infiltrate. Lung rises to the top of the list.

Anti tumor activity, yes, I'll two would be an obvious thing to add.

With the dose.

Got it and then maybe if I could get a last question then.

You talked about Jeff Miller.

Presenting it to see.

What do you think is the biggest differentiator of your platform versus donor derived NK cells.

As it non cleavable CV 16 component that you've talked about or is it or is there some other component.

Our next year.

The platform generally just some color on the.

The platform generally I think there's a month.

Who'd have factors that differentiate this platform I mean, we spoke a little while ago about just the nature of engineering.

Scott Walshco: Got it. And then I guess you also mentioned that you may amend for cytokine support. So are you thinking about, you know, administering IL-2 after dosing these cells? Yes. Yes.

I fundamentally believe cell therapy.

We'll incorporate multiple engineering elements to best promote anti tumor activity and I.

Scott Walshco: I mean, that's historically what has been done with donor-derived NK cell therapy. And I believe it's also done with a particular till therapy that everyone has sort of people's attention right now. IL-2 is commonly given with, and so when we think about amending the protocol to now promote NK cell anti-tumor activity, yes, IL-2 would be an obvious thing to add to the dose. Got it. And then, maybe I could get a last question in. You talked about Jeff Miller, you know, presenting at CITSE.

I believe that is going to be very hard will complex.

At scale.

In a predictable way and produce homogeneous product if those edits are occurring batch by batch as part of the manufacturing process.

I think thats going to be super challenging not to mention super expensive.

That's so the engineering is one element because weve collapsed all the engineering into a onetime event at a master cell line.

I do believe in the world of cancer immunotherapy, just like oncology. There's very few agents that are given as a single administration and there's going to be plenty of data and there is plenty of data coming out with car T cell therapy talking about the challenges of single dose administration.

Scott Walshco: What do you think is the biggest differentiator of your platform versus donor-derived NK cells? Is it, you know, the non-cleavable CD16 component that you've talked about, or is there some other component that you feel differentiates it? The platform generally, I think there's a multitude of factors that differentiate this platform. I mean, we spoke a little while ago about just the nature of engineering. I fundamentally believe cell therapy... will incorporate multiple engineering elements to best promote anti-tumor activity. And I believe that is going to be very hard to accomplish at scale, in a predictable way and produce a homogeneous product if those edits are occurring batch by batch as part of a manufacturing process.

In single antigen targeting that is leading to relapses and lack of durable responses and so to me the idea of being able to give multiple doses over multiple cycles like monoclonal antibodies are given.

But doing that with a cell therapy, where you can now engineer in multiple mechanisms of action.

I don't know any other way to do this other than Usan IPO cell based approach.

Great. Thank you.

Sure.

Our next question coming.

Jim.

Hi, Michael Your line is open.

Hi, guys. Thanks for all the detail it's just.

On high level question across Ft, 505, Onesix and 596, what's going to be the best opportunity tight densify the efficacy of the cell therapy itself.

Scott Walshco: I think that's going to be super challenging, not to mention super expensive. The engineering is one element because we've collapsed all the engineering into a one-time event at a master salon. I do believe in the world of cancer immunotherapy, just like oncology, there are very few agents that are given as a single administration. And there's going to be plenty of data, and there is plenty of data coming out with CAR-T cell therapy, talking about the challenges of single-dose administration, single-antigen targeting that is leading to relapses and lack of durable response. And so, to me, the idea of being able to give multiple doses over multiple cycles, like monoclonal antibodies... But doing that with a cell therapy where you can now engineer in multiple mechanisms of action, I don't know any other way to do this other than using an IPS cell-based approach. Great, thank you.

So.

I don't think it's a fair question quite honestly with respect to the product candidates I mean, 596, I mean, you're sitting here talking about three different functional modalities being embedded into it. So it's not a fair flight some basic level between the three product candidates.

So, but given that I guess what.

I'm trying to understand with 596, it sounds like we're moving into a were talks and combo pretty quickly if theyre going to be a good opportunities assessed monotherapy activity of the sells at a reasonable dose and and benchmark it against what we've seen from the car NK data from MD Anderson as an example.

There there may be but thats not our objective our objective is our belief that multi antigen targeting as a best in class approach I don't think word alone in that belief and ft. Fivenine six was designed to exploited.

Scott Walshco: Sure. Our next question comes from the line of Jim Brisendorf, ago, Yolanda Selby. Hi guys.

And Thats, where were and then maybe just.

Just thinking about the Rituxan combinations could you maybe speak to how many patients you need to treat or what level of response, you need to see to rule out contribution from Rituxan and I get the point that you have maybe responses in some patience as low as 10% to 20% but.

Scott Walshco: Thanks for all the detail. It's just one high-level question. Across FT500, 516, and 596, what's going to be the best opportunity to identify the efficacy of the cell therapy itself? Um, so I don't think it's a fair question, quite honestly, with respect to the product candidates.

Need to treat quite a few patients to rule out.

That levels response at the lower bound of confidence intervals could you speak to that because like tickets at some point, we're going to be trying to figure out the contribution of the cells and the antibody.

Scott Walshco: I mean, FT-596, you're sitting here talking about three different, you know, functional modalities being embedded into it, so, you know, it's not a fair fight at some basic level between the three product candidates. So, but given that, I guess, what I'm trying to understand with 596, it sounds like we're moving into a Rituxan combo pretty quickly. Is there going to be a good opportunity to assess the monotherapy activity of the cells at a reasonable dose and benchmark it against what we've seen from the CAR-NK data from MD Anderson, as an example? There may be, but that's not our objective.

In this data going forward.

Well to be clear they will have failed or toxin.

And with the definition of protection failure.

So the definition of a toughmet Baylor quite simply as a patients who received prior with Toughmet based therapy and either did not respond to that or progressed. Following an initial response.

So as just as a kind of a rough benchmark. If you look at what are the monoclonal antibody clinical experience in this patient population. There basically two examples one is single agent open a to them up and the others. The is the single agent more to eight that's the Cdnineteen directed monoclonal antibody from Morphoses.

Both.

Molecules have been tested a single agent in a patient population of failed rituximab and it's been fairly consistent in diffuse large b cell lymphoma, a complete response rate for both as ranges are approximately 10% best overall response is about 30, 35% those numbers are little bit higher in some of them.

Scott Walshco: Our objective is a belief that multi-antigen targeting is a best-in-class approach. I don't think we're alone in that belief, and FT-596 was designed to exploit us. And that's what we're going to do. Just thinking about the Rituxan combinations, could you maybe speak to how many patients you need to treat or what level of response you need to see to rule out contribution from Rituxan? And I get the point that you might have responses in some patients as low as 10 to 20%, but you need to treat quite a few patients to rule out that level of response at the lower bound of confidence intervals. Could you speak to that?

Indolent lymphomas, so as we do our initial assessment.

55, Onesix NFC Fivenine six those are the rock rough benchmarks that we used to see whether or not theirs.

Additional activity of conferred by that sell product, but to your point in order to rigorously rule that out we would have to do it in an expansion cohort with the requisite number of patients to rollout that lower bound.

But I would also just reiterate to be clear.

As Wayne discussed the target product profile for 15 596, if we're looking for I would say CMO. Her response rates that have been achieved with car T cell therapy.

Scott Walshco: Because I think it's at some point we're going to be trying to figure out the contribution of the cells and the antibody in this data going forward. Well, to be clear, they will have failed Rituximab, and the definition of retoxin failure. So the definition of rituximab failure is, quite simply, a patient who received prior rituximab-based therapy and either did not respond to that or progressed following an initial response.

Got it okay. That's terrific. Thanks, thanks for the follow up.

Our next question coming from the line.

And with Mizuho Your line is open.

Great. Thanks very much.

So I have a couple of questions going on on the S&P 500 program, what higher number of Gareth that engage our has received so far in the trial or is that something that you're going to disclose at ash.

And then I'm curious if you could characterize for.

And then Fysixteen program, what mild cytokine support.

And thirdly.

A question come.

Hi, Craig its regulatory question and that has taken a rig in your interaction with FDA and discussion characterizing.

Yes, you're right so product.

Okay on Curtis.

Typically and and and functionality.

Scott Walshco: So just as a kind of a rough benchmark, if you look at the monoclonal antibody clinical experience in this patient population, there are basically two examples. One is single-agent ocituzumab, and the other is single-agent MOR-208. That's the CE19-directed monoclonal antibody from morphosis. Both molecules have been tested as a single agent in a patient population of failed rituximab.

Correct Miss versus.

What does that access Craig.

So I'll I'll sort of going reverse.

There is a.

Tremendous amount that goes into.

The regulatory discussions with respect to clearing and investigational new drug application for clinical study.

There are multiple elements that are important.

I will tell you that.

Scott Walshco: And it's been fairly consistent in diffuse large basal lymphoma. The complete response rates for both ranges are approximately 10%. The best overall response is about 30%, 35%. Those numbers are a little bit higher in some of the more indolent lymphomas.

Characterizing the engineering events is absolutely characterizing the effective engineering the integrity of engineering is absolutely important.

Safety is absolutely important.

And there's a whole host of.

Scott Walshco: So as we do our initial assessment of FT516 and FT596, those are the rough benchmarks that we use to see whether or not there's additional activity that's conferred by the cell product. But to your point, in order to rigorously rule that out, we would have to do it in an expansion cohort with the requisite number of patients to rule out that lower bound. But I would also just reiterate, to be clear, as Wayne discussed, the target product profile for FTE-596. We are looking for, I would say, similar response rates that have been achieved with CAR T cell therapy. Okay. That's terrific.

Factors that go into putting together the regulatory package and demonstrating to the FDA that we have a product that we believe is safe to justify clinical study.

And engineering certainly one of those elements looking at the engineered features yes, and being able to characterize the product with respect to those features I think is really important and as I think it's one of the areas where were aided by the fact that ultimately we can chase trace the final product back to a single clone, which ensures uniformity of those engineered.

Heaters.

I'll, let Wayne talk about the clinical experiences with 50 565 16 ft 500, the clinical protocol with up to 500 initially in its initial form.

Scott Walshco: Thanks for the follow-up. Our next question comes from the line of Mara Goldstein with Missouho. Your line is open. Great. Thanks very much.

Was written to allow for up to six doses. So three doses in the first cycle three doses in the second cycle right that was that is how it was originally written for the for the first part of dose escalation.

Scott Walshco: So, I have a couple questions. One on the FT500 program. What's the highest number of doses that an individual has received so far in the trial, or is that something that you're going to disclose at ASH? And then I'm curious if you could characterize for us in the 516 program what mild cytokine support means. And thirdly, just a question from a quasi, I guess, regulatory perspective, and that has to do with your interaction with FDAs and sort of discussion and characterizing iPSC-derived cell products. Is the focus on sort of phenotypical and functionality correctness versus safety, and what does that access look like? So I'll sort of go in reverse. There is a.

And then with respect of Ft 516, this that dose and schedule of iPhone Sixs similar in the sense that it's three weekly doses per treatment cycle given on day, one day in day 15 of each treatment cycle, and then patients would be eligible to receive up to two treatment cycles. So that would mean.

Six total doses of Ft 516, and then your specific question around cytokine support it would be aisle to given added dose of 6 million international units given subcutaneously with each dose of ft 506. So there will be a total of up to six doses of aisle to support.

Scott Walshco: There is a tremendous amount that goes into the Regulatory Discussion with respect to clearing an investigational new drug application for clinical study. There are multiple elements that are important. I will tell you that... Characterizing the engineering events, characterizing the effect of engineering, the integrity of engineering is absolutely important.

For the 50 506 clinical trial.

Thanks, Brian .

Our next question coming from the line.

Scott Walshco: Safety is absolutely important, and there's a whole host of factors that go into putting together the regulatory package and demonstrating to the FDA that we have a product that we believe is safe enough to justify clinical study. Engineering is certainly one of those elements.

Great.

Ed.

Your line is open.

Great. Thank you.

Good discussions thus far one more question for me, maybe taking it back to the very first a question with more and more competitors coming in.

Scott Walshco: Looking at the engineered features, yes, and being able to characterize the product with respect to those engineered features is really important, and I think it's one of the areas where we're aided by the fact that, ultimately, we can trace the final product back to a single clone, which ensures the uniformity of those engineered features. I'll let Wayne talk about the clinical experiences with FT-516. FT-500, the clinical protocol with FT-500 initially, in its initial form, was written to allow for up to six doses, so three doses in the first cycle, three doses in the second cycle. That is how it was originally written for the first part of dose escalation. And then with respect to FT516, the dose and schedule of FT516 is similar in the sense that it's three weekly doses per treatment cycle given on day one, day eight, and day fifteen of each treatment cycle.

I think as a testament to your approach and the value that you've been talking so much about how do you think we should start comparing the data as it comes out from these competitors, but things in particular do you think are most interesting and helpful to compare pre clinically both for the IPO sees as well as the car.

NK competitors that that start to come.

So were discussed just to be clear, we're discussing preclinical data because I don't think we'll be discussing clinical data from a competitor for probably exactly no agree we're going to and we're going to recycle the preclinical data. So how should we judge that and your perspective and compare it to your programs Preclinically.

Sure I mean, I'll, let Bob answer that question, because Bob has sort of the greatest purview of what people are trying argues that we're trying to do in the IP FC field.

Hi.

Well, one thing I'll say before turning over to Bob as much as people have talked about IPO cell technology. I mean, we have spoken a lot about the value of selecting a single clone and we believe there's a lot of value to that.

Scott Walshco: And then patients would be eligible to receive up to two treatment cycles, so that would mean six total doses of FT516. And then your specific question around cytokine support, it would be IL-2 given at a dose of 6 million international units given subcutaneously with each dose of FT516, so there would be a total of up to six doses of IL-2 support in the FT516 clinical trial. Okay, thanks a

I still have not seen anyone talk about being able to select a single clone and making master cell bank I still have not seen that from one person.

So when you see that let me know, but I'll, let Bob.

I'll, let Bob go.

Thats a good question and then Scott kind of started it we've been talking about at the whole time I mean, I think you can think about in four stages. The first stage is exactly what Scott said, you make that math to sell bank and massive felt banks and generate from a single cell authentiguard any of your master cell Bank, how we'll have you characterized it.

Scott Walshco: Our next question comes from the line of Daina Graybosch. Great, thank you. Good discussion thus far. One more question from me, maybe going back to the very first question. With more and more competitors coming in, I think as a testament to your approach and the value that you've been talking so much about, how do you think we should start comparing the data as it comes out from these competitors? What things in particular do you think are most interesting and helpful to compare preclinically both for the IPSCs as well as the CAR-NK competitors that are starting to come?

And do you have genomics stability after netting massive expansion.

So first stage one generation of the massive fell bank that contention modalities in a uniform manner that as.

Well characterized the second stages and any specific differentiation how low can you take that vial that you've created in the master cell Bank and then guided through differentiation to make yourself. The final cell product have fully mature tiering NK cell that has the ability to do exactly what you told that are you engineer to do that the second stage.

Scott Walshco: So, just to be clear, we're discussing preclinical data because I don't think we'll be discussing clinical data from a competitor for probably two years. Exactly. No, I agree.

Scott Walshco: We're going to be stuck with preclinical data, so how should we judge that from your perspective and compare it to your programs preclinically? Sure. I mean, I'll let Bob answer that question because Bob has sort of the greatest purview of what, you know, people are trying, I'll use the word trying, to do in the IPSC field. But one thing I'll say before turning it over to Bob, as much as people have talked about IPS cell technology, I mean, we have spoken a lot about the value of selecting a single clone, and we believe there's I still have not seen anyone talk about being able to select a single clone and make a master cell bank. I still have not seen that from any person.

Last year manufacturing process to create homogeneous process product every time that as of desired attribute.

Third stage of that is now the distribution of that off the shelf product can you directly thawing fuse can you make the back can you shipped to the hospitals and can you go through that all that stability all the things that the regulatory challenges and manufacturing operations the clinical logistics, so thats the to off the shelf stage and then finally as the product itself.

I think on the things that we were very proud of its not just the manufacturing of IPO says that the intelligence that goes behind product development. This dual targeting approach is something that working with Michel satellite Jeff Miller, another collaborators that Kaufman Kelly Melbourne, we've been able to put together I think as next year rolls out you'll see more.

Scott Walshco: So when you see that, let me know, but I'll let Bob, I'll let Bob go. So that's a great question. And Scott kind of started it, and we've been talking about it the whole time. I mean, I think you could think about it in four stages. The first stage is exactly what Scott said. When you make that master cell bank, and that master cell bank's been generated from a single cell, what's the integrity of your master cell bank? How well have you characterized it? And do you have genomic stability after that massive expansion?

Siding products that our entry point into solid tumor for example, so the actual modalities you put in and it's also going to be acquiring so if you look at those four unique stages.

I don't think anybody today can say, we got it all puffer and it let me think we're here, saying that we think we've got all coverage because I've been doing this with 12 years now.

I guess thing that I would add from just a more practical regulatory perspective, I mean, one of the thing I was asked about actually Didnt touch on us.

Scott Walshco: So, stage one is the generation of the master cell bank that contains your modalities in a uniform manner that is well characterized. The second stage is lineage-specific differentiation. How well can you take that vial that you've created in the master cell bank and then guide it through differentiation to make the final cell product? A fully matured tRNA case cell that has the ability to do exactly what you told it, or you engineered it to do? So that's the second stage. And then the third stage is your manufacturing process to create a homogeneous product every time that is of desired attributes. The third stage of that process is now the distribution of that off-the-shelf product. Can you directly thaw and infuse it? Can you make the bags? Can you ship them to the hospitals?

You have an IPO sell right that I'd DSL has the potential walk down arguably 200 different.

As of life.

The.

Purity of your final product.

Is going to be critical and we've discussed our purity levels.

And then as Bob sort of touched on the potency post fall.

You have and truly have an off the shelf product is also going to be critical.

So when people, we and talk about preclinical data in mice and all that kind of good stuff, but when you have a scalable manufacturing process that starts with a genomically stable master cell line that's colonial.

Scott Walshco: And can you go through all that stability, all the things that regulatory challenges of manufacturing operations, clinical logistics? So that's the off-the-shelf stage. And then finally, is the product itself. I think one of the things that we've been very proud of is not just the manufacturing of iPSCs but the intelligence that goes behind product development. This dual-targeting approach is something that, working with Michelle Satterlein, Jeff Miller, and other collaborators, Dan Kaufman, and Kelly Malberg, we've been able to put together. And I think as next year rolls out, you'll see more exciting products that are entry points into solid tumors, for example. So the actual modalities you put in are also going to be important. So if you look at those four unique stages, I don't think anybody today can say we've got it all covered.

And when you have a final product candidate that is almost pure coming out of manufacturer with high potency post fall.

Let me know.

But curious to look at that data.

It's ours.

Great. Thank you very much for that.

No not showing any further questions at this time.

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

Closing remarks.

Great. Thank you everyone for participating on today's call. We look forward to seeing you in the next couple of weeks, including it sits in our ash investor event.

Thank you.

Ladies and gentlemen. This concludes today's conference call. Thank you for participating you may all disconnect have a good day.

Scott Walshco: And the only reason we're here is because we think we have it all covered is because we've been doing this for 12 years now. I think that I would add from just a more practical regulatory perspective. I mean, one of the things I was asked about, and I actually didn't touch on this. You know, you have an iPS cell, right? That iPS cell has the potential to walk down, arguably, 200 different paths of life. The security of your final product is going to be critical, and we've discussed our purity levels. And then, as Bob sort of touched on, the potency post-thaw, if you truly have an off-the-shelf product, is also going to be critical.

Scott Walshco: So when people, we didn't talk about preclinical data and mice and all that kind of good stuff, but when you have a scalable manufacturing process that starts with a genomically stable master cell line that's clonal, and when you have a final product candidate that is almost pure coming out of manufacture with high potency, post-thaw... Let me know. I'd be curious to look at that data.

Scott Walshco: Great. Thank you very much for that. I'm not showing any further questions at this time; I would now like... Please call back over to Mr. Scott Walshko for closing remarks. Great. Thank you everyone for participating in today's call, and we look forward to seeing you in the next couple weeks, including at CITSE for our Ash Investor event. Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.