Q1 2022 Sangamo Therapeutics Inc Earnings Call

May 5, 2022

[music].

Thank you for standing by, and welcome to Sangamo's first quarter 2022 teleconference call.

Thank you for standing by and welcome to <unk> first quarter 2020 do teleconference call.

At this time, all participant lines are in listen-only mode.

Thank you for participating.

I'm all participants' lines are in listen only mode.

After the speaker's presentation, there will be a question and answer session.

The speaker's presentation, there will be a question and answer session to ask a question. During the session. You will need your breasts are wanting your telephone. Please be advised that today's conference is being recorded if you require any further assistance. Please press star zero.

To ask a question during the session, you'll need to press star 1.

Please be advised that today's conference is being recorded.

If you require any further assistance, please press star zero.

I would now like to hand the conference over to your speaker today, Ms. Louise Wilkie.

You may now, Thank you for standing by, and welcome to Sangamo's first quarter 2022 teleconference call.

I would now like to hand, the conference over to your Speaker today Ms. Lewis Wilkie. Thank you. Please go ahead.

Thank you.

At this time, all participant lines are in listen-only mode.

Good afternoon, and thank you for joining us today with me on the call. This afternoon, Sandy Macrae Chief Executive Officer.

Mcclung Chief operating officer.

Sure.

Financial Officer, Jason <unk>, Chief Scientific Officer rupture.

Relevant and Bettina Cockroft, Chief Medical Officer.

Please go ahead.

Slides from our corporate presentation can be found at our website Banco <unk> dot com under the investors and media section of the events and presentation page.

This call includes forward looking statements regarding <unk> current expectations. These statements include but are not limited to statements related to the therapeutic and commercial potential of our product candidates the anticipated plans and timelines for Sangamo and our collaborators for initiating in conducting clinical trials in presenting clinical data.

Execution of our corporate strategy advancement of our product candidate <unk>.

2022 financial guidance and other statements that are not historical facts.

Actual results may differ materially from what we discuss today.

Statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC.

Typically on a quarterly report on Form 10-Q for the fiscal quarter ended March 31 2022.

Our annual report on Form 10-K for the fiscal year ended December 31 2021.

The forward looking statements stated today are made as of the states and we undertake no duty to update such information, except as required by law.

On this call we discuss non-GAAP operating expenses reconciliation of this measure to our GAAP operating expenses can be found in today's press release, which is available on our website.

Good afternoon, and thank you for joining us today.

After the speaker's presentation, there will be a question and answer session.

Now I'd like to turn the call over to our CEO Sandy Macrae. Thank you Luis and good afternoon to everyone on the call.

With me on the call this afternoon are Sandy Macrae, Chief Executive Officer, Mark McClung, Chief Operating Officer, Prathyusha Duraibabu, Chief Financial Officer, Jason Fontenot, Chief Scientific Officer, Rob Schott, Head of Development, and Bettina Cockcroft, Chief Medical Officer.

To ask a question during the session, you'll need to press star 1.

Building on a year of significant clinical and preclinical progress in 2021 <unk> advance multiple programs in the first quarter of 2022 as we continue our mission to create transformative genomic medicines for patients using our innovative technologies.

Slides for my corporate presentation can be found at our website, sangamo.com, under the investors and media section of the events and presentation page.

This call includes forward-looking statements regarding Sangamo's current expectations. These statements include, but are not limited to, statements related to the therapeutic and commercial potential of our product candidates, the anticipated plans and timelines of Sangamo and our collaborators for initiating and conducting clinical trials and presenting clinical data, execution of our corporate strategy, advancement of our product candidates, our 2022 financial guidance, and other statements that are not historical facts.

Bydd y canlyniadau mewn gwirionedd yn wahanol o'r hyn rydyn ni'n ei drafod heddiw.

These statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC, specifically on our quarterly report on Form 10-Q for the fiscal quarter ended March 31, 2022, and our annual report on Form 10-K for the fiscal year ended December 31, 2021.

We are proud to have three programs progressing towards or in late stage development and to be the first company to us to dose a patient in what we believe is a completely new treatment modality.

This quarter, we do have three additional patients and our differentiated and wholly owned gene therapy program for the treatment of adults with fabry disease.

We have now successfully dosed a total of nine patients across four cohorts and the STAAR study to complete the dose escalation portion of the phase one two study.

We are delighted to have achieved this significant milestone and with recent changes in the competitive landscape continue to believe that we are in a leading position amongst gene therapy for fabry disease.

We look forward to presenting updated data in the second half of 'twenty two.

We in Sanofi dose.

Patient in the phase one two precision one study our zinc finger nucleus modified the <unk> cell therapy for the treatment of sickle cell disease.

The forward-looking statements stated today are made as of this date, and we undertake no duty to update such information except as required by law.

We expect to complete patient dosing in the third quarter of 2022 and.

And look forward to sharing an update on data in the second half of this year.

Regarding the phase III hemophilia, a gene therapy trial, Pfizer announced in March the FDA lifted the clinical hold that have been pleased when they are fighting trial.

Pfizer announced that dosing will resume once all necessary conditions are met including approval of updated trial protocols by regulatory authorities.

Pfizer anticipate resuming the trial in the third quarter of 2002 with a pivotal data readout estimates in the second half of 2023.

In March Sangamo dose the first patient in our phase one two steadfast clinical study evaluating TX 200, our wholly owned <unk> car T. Reg cell therapy product candidate for the prevention of immune mediated rejection and easily <unk> mismatched kidney transplantation from a living donor.

We are thrilled to have achieved this momentous milestone, which we believe is a first in human dosing of an engineered car T Reg cell therapy candidate.

Most importantly, the patient continues to be well.

It has not reported any adverse events related to the treatment to date.

We are planning to dose the second patient in the steadfast study around the middle of 'twenty two based on their transplants schedule I'm looking forward to sharing the appropriate data at the right time.

On this call, we discuss our non-GAP operating expenses. Reconciliation of this measure to our GAP operating expenses can be found in today's press release, which is available on our website.

Please be advised that today's conference is being recorded.

Before providing more detail on these programs I want to note that these advancements have resulted from our strategic and focused use of research and development capabilities, which are supported by our in house infrastructure, including AAV and cell therapy manufacturing facilities.

We believe that this positions us well to create new transformative medicines for patients in need and to generate long term value for our shareholders.

With that I'd like to head over turnover the call to our head of development rope short, who will outline the progress of our clinical programs in more detail. Thank.

Now I'd like to turn the call over to our CEO, Andy Macrae.

If you require any further assistance, please press star zero.

Thank you Sandy and good afternoon to everyone on the call.

Thank you, Louise, and good afternoon to everyone on the call.

Our development organization remains focused on execution in the clinic and we are pleased with this quarter's progress.

Building on a year of significant clinical and preclinical progress in 2021, Sangamo advanced multiple programs in the first quarter of 2022 as we continue our mission to create transformative genomic medicines for patients using our innovative technology.

I would now like to hand the conference over to your speaker today, Ms. Louise Wilkie.

<unk> with our phase one two star study examining is routed Jean <unk> or <unk>, which is our wholly owned gene therapy program for the treatment of fabry disease in adults.

We are proud to have three programs progressing towards or in late-stage development and to be the first company known to us to dose a patient in what we believe is a completely new treatment modality. This quarter, we dose three additional patients in our differentiated and wholly owned gene therapy program for the treatment of adults with Fabry disease.

Thank you.

We have now successfully dosed a total of 9 patients across 4 cohorts in the STAR study to complete the dose escalation portion of the Phase 1-2 study.

Please go ahead.

This quarter the safety monitoring committee approved escalating to a fourth dose cohort as outlined in the STAAR study protocol.

We are delighted to have achieved this significant milestone and with recent changes in the competitive landscape, continue to believe that we are in a leading position amongst gene therapies for Fabry disease.

Good afternoon, and thank you for joining us today.

This was based on the totality of data from the previously dose patients.

Two patients have since been dosed in cohort four at the 513.

Victor genomes per kilogram dose level, completing the dose escalation portion of this phase one two study.

Furthermore, this quarter, we dosed an additional patient in cohort three.

<unk> achieved a total of three patients in this cohort and nine patients overall that had been dosed in the STAAR study to date.

In addition, during this quarter, we completed withdraw of enzyme replacement therapy from a second patient, which means that we now have withdrawn one each from the first and second cohorts.

Patients are being closely monitored and investigators have thus far not deemed it necessary to resume enzyme replacement therapy we.

We look forward to presenting updated data in the second half of 2022.

We expect to provide updated results from the STAAR study in the second half of 2022 and are actively preparing for both the phase two expansion cohorts in a phase III clinical trial.

We in Sanofi dosed a fifth patient in the Phase 1 to Precision 1 study.

In the phase one tube precision one study of <unk> <unk> six for the treatment of sickle cell disease. This quarter, we dosed. The first patient. This patient was the first in the study to receive a product candidate manufactured using improved methods that have been shown in internal experiments to increase the number of law.

Our zinc finger nucleus modified autologous cell therapy for the treatment of sickle cell disease.

Long term progenitor cells in the final product.

Expect to dose the remaining patients in this study in the third quarter of this year, we look forward to sharing an update on the precision one study in the second half of 2022 feet.

We expect to complete patient dosing in the third quarter of 2022 and look forward to sharing an update on data in the second half of this year.

Feedback has been received from the FDA in phase III, enabling activities, including manufacturing readiness are in progress.

The orderly transition of Sanofi has rights and obligations under this program back to Sangamo is progressing well and is on track to be completed on June 28.

As previously outlined Sangamo is excited to have this asset back in our hands soon.

Regarding the Phase 3 Haemophilia A gene therapy trial, Pfizer announced that in March the FDA lifted the clinical hold that had been placed on the Affine trial. Pfizer announced that dosing will resume once all necessary conditions are met, including approval of updated trial protocols by regulatory authorities. Pfizer anticipates resuming the trial in the third quarter of 2022, with a pivotal data readout estimated in the second half of 2023.

Slides for my corporate presentation can be found at our website, sangamo.com, under the investors and media section of the events and presentation page.

As sandy outlined in his opening Pfizer recently announced that in March of this year. The FDA lifted its clinical hold on the phase III trial evaluating evaluating <unk> <unk>, an investigational gene therapy for hemophilia a.

The hold was put in place following the observance of factor eight expression levels greater than 150% in some treated participants <unk>.

Pfizer has announced that the voluntary pause remains in place until all necessary conditions are met.

<unk> approval of an updated trial protocols by regulatory authorities.

In addition, Pfizer was made aware of a below the knee deep venous thrombosis and one participant with elevated factor eight levels. This patient had a history of thrombotic events prior to participation in the trial, which is a known risk factor for subsequent events and an exclusion criterion for participation in the <unk> trial.

The case was the SaaS to understand all potential contributing factors, including missed doses of investigator prescribed direct oral anticoagulant.

The patient is reported to be doing well.

All study participants continue to be closely monitored and there have been no. Other thrombotic events reported in the study at this time. The information was shared with study investigators health authorities and the independent external data monitoring committee and Pfizer responding to queries from health authorities.

Pfizer and Sangamo remain committed to the hemophilia community and Pfizer anticipate resuming the trial in the third quarter of 2022 with a pivotal data readout estimated in the second half of 2023.

In March, Sangamo dosed the first patient in our Phase 1-2 Steadfast Clinical Study, evaluating TX200, our wholly-owned autologous CAR Treg cell therapy product candidate, for the prevention of immune-mediated rejection in HLA-A2 mismatched kidney transplantation from a living donor. We are thrilled to have achieved this momentous milestone, which we believe is the first in human dosing of an engineered CAR Treg cell therapy candidate. Most importantly, the patient continues to be well, and has not reported any adverse events related to the treatment to date.

This call includes forward-looking statements regarding Sangamo's current expectations.

In the first quarter Sangamo also had significant and Trailblazing development on our wholly owned TX 200 car T. Reg cell therapy candidate for the prevention of immune mediated rejection in HLA <unk> mismatch kidney transplantation from a living donor on March 22nd we dust.

We're planning to dose the second patient in the Steadfast study around the middle of 22 based on their transplant schedule.

These statements include, but are not limited to, statements related to the therapeutic and commercial potential of our product candidates, the anticipated plans and timelines of Sangamo and our collaborators for initiating and conducting clinical trials and presenting clinical data, execution of our corporate strategy, advancement of our product candidates, our 2022 financial guidance, and other statements that are not historical facts, gall y canlyniadau mewn gwirionedd ddifrif o'r hyn rydyn ni'n ei drafod heddiw. These statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC.

The first patient in our phase one two steadfast clinical study and what we believe is the first ever dosing of a human with a car T. Reg cell therapy candidate continuing <unk> track record of advancing groundbreaking ceremony of therapies and genomic medicine.

I'm looking forward to sharing the appropriate data at the right time.

Specifically, on a quarterly report on Form 10-Q for the fiscal quarter ended March 31, 2022, and our annual report on Form 10-K for the fiscal year ended December 31, 2021.

Before Rob provides more detail on these programmes, I want to note that these advancements have resulted from our strategic and focused use of research and development capabilities, which are supported by our in-house infrastructure, including AAV and cell therapy manufacturing facilities.

The forward-looking statements stated today are made as of this date, and we undertake no duty to update such information, except as required by law.

The patient continues to do well following dosing with the autologous car T. Reg therapy, and it has not reported any adverse events related to the treatment to date as you know safety and Tolerability continue to be among the major goals of the phase one two study.

On this call, we discuss our non-GAP operating expenses. Reconciliation of this measure to our GAP operating expenses can be found in today's press release, which is available on our website.

We believe that this positions us well to create new transformative medicines for patients in need and to generate long-term value for our shareholders.

With that, I'd like to head over, turn over the call to our Head of Development, Rob Schott, who will outline the progress of our clinical programs in more detail.

Now I'd like to turn the call over to our CEO, Andy Macrae.

Thank you, Sandy, and good afternoon to everyone on the call.

Thank you, Louise, and good afternoon to everyone on the call.

TX 200 was designed with the potential to prevent kidney rejection by reducing local inflammation and promoting immunological tolerance to the graft. This investigational cell therapy is composed of autologous T. Reg cells engineered to express an HLA <unk> car and is being assessed in the <unk> <unk> to <unk>.

<unk> patients receiving a mismatched HLA <unk> positive kidney from a living donor.

TX 200 engineered car T regs are expected to localized to the graft and activate upon binding the HLA <unk> antigen.

Through their ability to regulate the immune system, TX 200 cells may protect the graft for immune mediated rejection and reduce or eliminate the need for lifelong treatment with immunosuppressants.

Our development organization remains focused on execution in the clinic, and we are pleased with this quarter's progress.

And the steadfast clinical study design, each patient undergoes a leukapheresis procedure to quicker white blood cells, which after T. Reg cells are isolated or genetically engineered and cryo preserved the patient subsequently undergone transplantation surgery to receive a kidney from a living donor.

Beginning with our Phase 1-2 STAR study examining Israelgic gene Sotoparvovec, or ST920, which is our wholly owned gene therapy program for the treatment of Febreze disease in adults. This quarter, the Safety Monitoring Committee approved escalating to a fourth dose cohort as outlined in the STAR study protocol. This was based on the totality of data from the previously dosed patients. Two patients have since been dosed in Cohort 4 at the 5E13 vector genomes per kilogram dose level, completing the dose escalation portion of the Phase 1-2 study. Furthermore, this quarter, we dosed an additional patient in Cohort 3. This achieves the total of three patients in this cohort and nine patients overall that have been dosed in the STAR study to date.

We are proud to have three programs progressing towards, or in, late-stage development and to be the first company known to us, to dose a patient, in what we believe is a completely new treatment modality. This quarter, we dose three additional patients in our differentiated and wholly owned gene therapy program for the treatment of adults with Fabry disease.

In addition, during this quarter, we completed withdrawal of enzyme replacement therapy from a second patient, which means that we now have withdrawn one each from the first and second cohorts. These patients are being closely monitored and investigators have thus far not deemed it necessary to resume enzyme replacement therapy.

We have now successfully dosed a total of 9 patients across 4 cohorts in the STAR study to complete the dose escalation portion of the Phase 1-2 study.

We expect to provide updated results from the STAR study in the second half of 2022 and are actively preparing for both the Phase 1-2 expansion cohorts and a Phase 3 clinical trial.

We look forward to presenting updated data in the second half of 2022.

In the Phase I-II, Precision I study of SAAR 445136 for the treatment of sickle cell disease, this quarter we dosed the fifth patient. This patient was the first in the study to receive a product candidate manufactured using improved methods, that have been shown in internal experiments to increase the number of long-term progenitor cells in the final product.

We in Sanofi dosed a fifth patient in the Phase 1-2, Precision 1 study.

Following a recovery period, the patient receives their individualized, TX 200 invasive investigational cell therapy.

Our zinc finger nucleus modified autologous cell therapy for the treatment of sickle cell disease.

We expect to complete patient dosing in the third quarter of 2022 and look forward to sharing an update on data in the second half of this year.

Regarding the phase 3 haemophilia A gene therapy trial, Pfizer announced that in March, the FDA lifted the clinical hold that had been placed on the affine trial. Pfizer announced that dosing will resume once all necessary conditions are met, including approval of updated trial protocols by regulatory authorities. Pfizer anticipates resuming the trial in the third quarter of 2022, with a pivotal data readout estimated in the second half of 2023.

We expect to dose the remaining patients in the study in the third quarter of this year.

In March, Sangamo dosed the first patient in our Phase 1-2 Steadfast Clinical Study evaluating TX200, our wholly-owned autologous CAR Treg cell therapy product candidate, for the prevention of immune-mediated rejection in HLA-A2 mismatched kidney transplantation from a living donor. We are thrilled to have achieved this momentous milestone, which we believe is the first in human dosing of an engineered CAR Treg cell therapy candidate. Most importantly, the patient continues to be well, and has not reported any adverse events related to the treatment to date.

Dosing of patients therefore occur several months after patient enrollment.

We look forward to sharing an update on the Precision One study in the second half of 2022. Feedback has been received from the FDA and Phase III enabling activities, including manufacturing readiness, are in progress.

Secondary objectives include the incidence of biopsy confirmed confirmed acute graft rejection incidence of chronic graft rejection and confirmation that TX 200 car T Reg cells localized to the transplanted kidney.

Also plan to evaluate the ability to reduce systemic immunosuppressive therapy, which carries the risk of significant systemic toxicity.

We're planning to dose the second patient in the Steadfast study around the middle of 22 based on their transplant schedule.

Sangamo expects to dose a second patient and the steadfast study around the middle of 2022 based on their transplant schedule and we plan to complete the first cohort which comprises a total of three patients by the end of the year, we look forward to sharing data at the appropriate time.

We see this study as the first step in our R&D journey towards a potential pipeline of car T. Reg therapies for autoimmune diseases. In addition to TX 200, Sangamo is developing car T. Reg cell therapy candidates in preclinical studies, including for potential use in treating multiple sclerosis, and inflammatory bowel disease.

Orders.

I'm looking forward to sharing the appropriate data at the right time.

I will now turn the call over to our Chief Scientific Officer, Jason Fox now for an update on our preclinical programs Jason.

The orderly transition of Sanofi's rights and obligations under this program back to Sangamo is progressing well and is on track to be completed on June 28th.

Before Rob provides more detail on these programmes, I want to note that these advancements have resulted from our strategic and focused use of research and development capability, which are supported by our in-house infrastructure, including AAV and cell therapy manufacturing facilities.

Thank you, Rob and good afternoon, everyone.

As previously outlined, Sangamo is excited to have this asset back in our hands soon.

We believe that this positions us well to create new transformative medicines for patients in need and to generate long-term value for our shareholders.

We continue to make strong progress across a range of preclinical programs based on our cutting edge genomic engineering platform.

Pfizer has announced that the voluntary pause remains in place until all necessary conditions are met, including approval of an updated trial protocols by regulatory authority.

In addition, Pfizer was made aware of a below-the-knee deep penis thrombosis in one participant with elevated factor eight levels. This patient had a history of thrombotic events prior to participation in the trial, which is a known risk factor for subsequent events and an exclusion criterion for participation in the affine trial. The case was assessed to understand all potential contributing factors, including missed doses of investigator prescribed direct oral anticoagulants. The patient is reported to be doing well.

All study participants continue to be closely monitored and there have been no other thrombotic events reported in the study at this time. The information was shared with study investigators, health authorities, and the independent external data monitoring committee, and Pfizer responded to queries from health authorities.

Pfizer and Sangamo remain committed to the hemophilia community, and Pfizer anticipates resuming the trial in the third quarter of 2022 with a pivotal data readout estimated in the second half of 2023.

With that, I'd like to head over, turn over the call to our Head of Development, Rob Schott, who will outline the progress of our clinical programs in more detail.

We're particularly pleased to recently announce second most significant presence at the upcoming American Society of gene and cell therapy, or <unk> annual meeting in Washington D C, which takes place later this month.

Thank you, Sandy, and good afternoon to everyone on the call.

We look forward to presenting a total of eight abstracts across three key areas.

Our development organization remains focused on execution in the clinic, and we are pleased with this quarter's progress.

Firstly, we will show the latest innovations in our genomic engineering platform, including our base editing program and the use of zinc finger transcription factors for multiplex engineering of car T cells without changes to the genetic code.

Secondly, we will highlight important advances in our AAV capsid engineering program, a critical component of our CNS focus in vivo genome engineering portfolio.

In the first quarter, Sangamo also had significant and trailblazing development on our wholly-owned TX200 CAR-T reg cell therapy candidate for the prevention of immune-mediated rejection in HLA-A2 mismatched kidney transplantation from a living donor. On March 22, we dosed the first patient in our Phase I-II Steadfast Clinical Study in what we believe is the first-ever dosing of a human with a CAR-T reg cell therapy candidate, continuing Sangamo's track record of advancing groundbreaking therapies in genomic medicine. The patient continues to do well following dosing with the autologous CAR Treg therapy, and it's not reported any adverse events related to the treatment to date.

And finally, our car T Reg cell therapy platform, including presentations on our TX 200 program and a presentation on our preclinical allogeneic T Reg Engineering program.

As you know, safety and tolerability continue to be among the major goals of the Phase 1-2 study. TX200 was designed with the potential to prevent kidney rejection by reducing local inflammation and promoting immunological tolerance to the graft.

For the full list of Sangamo.

<unk> accepted at http. Please see the press release, we issued earlier this week, which is available on the media and investors page of our website.

These abstracts are represented a robust sangamo research engine and our continuous drive to innovate and evolve our genomic engineering platform.

And privilege to work with a dedicated team responsible for this work.

Worked as the backbone of Sangamo strong long term pipeline that we believe can deliver innovative medicines to patients in need I.

I will now turn the call over to produce <unk> for an overview of our.

Financial results for <unk>.

This investigational cell therapy is composed of autologous Treg cells engineered to express an HLA2 CAR and is being assessed in the HLA2 negative patients receiving a mismatched HLA A2 positive kidney from a living donor. TX200 engineer CAR-T regs are expected to localize to the graft and activate upon binding the HLA-A2 antigen.

Thank you, Jason and good afternoon, everyone.

Our financial results for this quarter are available in the press release issued this afternoon, which can be found on our website.

This quarter, we continued to build on our 2021 investments, including advancement of our clinical programs, our preclinical research pipeline and optimization of our in house manufacturing capabilities.

We ended the quarter with approximately $400 million in cash cash equivalents and marketable securities.

We believe that our balance sheet remains strong with continued execution across our expected upcoming keep Texas.

Turning to 2022 full year guidance.

2022 full year non-GAAP operating expenses continues to be expected to be between $280 million to $310 million for the year.

This range excludes estimated noncash stock based compensation expense of approximately $14 million.

We expect a significant portion of our operating expenses to be invested and continued progress of our lead programs, including <unk>.

February phase III planning activities <unk> activities forgive 200.

And preclinical work and cocky right Mpls indications.

We also expect to grow our investments in sickle cell disease in the second half of the year pulling defense of the program back to Sangamo.

I'll now turn it back to Sandy for closing remarks. Thank.

Thank you Patricia.

Through their ability to regulate the immune system, TX200 cells may protect the graft from immune-mediated rejection and reduce or eliminate the need for lifelong treatment with immunosuppressants.

We expect to provide updated results from the STAR study in the second half of 2022 and are actively preparing for both the Phase I-II expansion cohorts and a Phase III clinical trial.

When we last spoke in February I sit our accomplishments in 2021, which sets us up for a strong 2022.

And I believe our momentum in the first quarter bears this out.

In the steadfast clinical study design, each patient undergoes a leukophoresis procedure to collect their white blood cells, which after Treg cells are isolated, are genetically engineered, and then cryopreserved.

We are a fully integrated genomic medicine company building momentum with our novel Science clinical execution and in house manufacturing.

The patient subsequently undergoes transplantation surgery to receive a kidney from a living donor.

The first quarter progress we have outlined demonstrates how this is coming together to create.

Amongst the patients were working to serve a significant opportunity for our company and the potential for long term sustainable value for our shareholders.

I am very grateful to my leadership team and all my <unk> colleagues for their dedication to.

And hard work towards our mission of creating new transformation genomic medicines for patients.

We look forward to expected key milestones and catalysts throughout the year, including.

Presentation of additional phase one to start data for Pat could you sees as well as the dosing of patients in the expansion cohorts.

In the Phase 1-2, Precision 1 study of SAR 445136 for the treatment of sickle cell disease, this quarter we dosed the fifth patient. This patient was the first in the study to receive a product candidate manufactured using improved methods, that have been shown in internal experiments to increase the number of long-term progenitor cells in the final product.

Dosing of the remaining patients in our phase one two precision one study for sickle cell disease, along with presentation of additional data from this study.

We expect to dose the remaining patients in the study in the third quarter of this year.

The orderly transition of Sanofi's rights and obligations under this program back to Sangamo is progressing well and is on track to be completed on June 28th.

Following the recovery period, the patient receives their individualized TX200 investigational cell therapy. Dosing of patients, therefore, occurs several months after patient enrollment. Secondary objectives include the incidence of biopsy-confirmed acute graft rejection, incidence of chronic graft rejection, and confirmation that TX200 CAR-T reg cells localize to the transplanted kidney.

Dosing of additional patients in our phase one two TX 200 car T. Reg steadfast study and pfizer's potential resumption of the pivotal phase III <unk>.

Trial in hemophilia a.

We also plan to evaluate the ability to reduce systemic immunosuppressive therapy, which carries the risk of significant systemic attacks.

Operator.

Sangamo expects to dose a second patient in the STEDFAST study around the middle of 2022 based on their transplant schedule, and we plan to complete the first cohort, which comprises a total of three patients, by the end of the year.

Please open the line for questions.

We look forward to sharing data at the appropriate time.

As previously outlined, Sangamo is excited to have this asset back in our hands soon.

As a reminder to ask a question. Please press star one your telephone and can we get a question. Please press <unk>.

We see the study as the first step in our R&D journey towards a potential pipeline of CAR Treg therapies for autoimmune diseases.

As Sandy outlined in his opening, Pfizer recently announced that in March of this year, the FDA lifted its clinical hold on the phase three affine trial, evaluating Garotagene-fidoparvovac, an investigational gene therapy for hemophilia A. The hold was put in place following the observance of factor VIII expression levels greater than 150 percent in some treated participants. Pfizer has announced that the voluntary pause remains in place until all necessary conditions are met, including approval of an updated trial protocols by regulatory authorities.

In addition to TX200, Sangamo is developing CAR Treg cell therapy candidates in preclinical studies, including for potential use in treating multiple sclerosis and inflammatory bowel disorders.

Again to ask a question. Please press star one at telephone Keypad, Anthony Joe a question. Please press <unk>.

I will now turn the call over to our Chief Scientific Officer, Jason Fontenot, for an update on our preclinical programs.

In addition, Pfizer was made aware of a below-the-knee deep venous thrombosis in one participant with elevated factor eight levels. This patient had a history of thrombotic events prior to participation in the trial, which is a known risk factor for subsequent events and an exclusion criterion for participation in the affine trial.

Lisa and I will be compile the Q&A roster.

The case was assessed to understand all potential contributing factors, including missed doses of investigator prescribed direct oral anticoagulants.

The patient is reported to be doing well.

Our first question comes from the line of Yanan, Zhu from Wells Fargo.

Jason.

Hi, Thanks for taking my questions.

Thank you, Rob, and good afternoon, everyone.

Congrats on all the progress this quarter.

We continue to make strong progress across a range of preclinical programs based on our cutting-edge genomic engineering platform.

I have a few questions, but relatively quick ones.

We're particularly pleased to recently announce Sangamo's significant presence at the upcoming American Society of Gene and Cell Therapy, ASGCT, annual meeting in Washington, D.C., which takes place later this month. We look forward to presenting a total of eight abstracts across three key areas.

Our <unk> program.

Secondly, we will highlight important advances in our AAV capsid engineering program, a critical component of our CNS focus in vivo genome engineering portfolio.

And finally, our CAR T-REG cell therapy platform, including presentations on our TX200 program and a presentation on our preclinical allogeneic T-REG engineering program, for the full list of Sangamo ad tracts accepted at ASG.

It sounds like two patients have been all CRT.

Please see the press release we issued earlier this week, which is available on the Media and Investors page of our website.

These abstracts are representative of the robust Sangamo research engine and our continuous drive to innovate and evolve our genomic engineering platform.

I'm privileged to work with the dedicated team responsible for this, worked as the backbone of Sangamo's strong, long-term pipeline that we believe can deliver innovative medicines to patients.

Congratulations on that finding and could you share the duration.

Four.

These are both are.

Longer patients and also what is the criteria for restarting PRT is it like a lessor can be three level at baseline or is it.

LIFO GPT level.

And then on the hem.

B program I have very quick.

Question, whether that case has been communicated with regulators and then I have a.

One question on the base editor program. Thank you.

I will now turn the call over to Prathyusha for an overview of our financial results.

Thank you lots of great questions here, so im going to distribute tier and so bettina will take on the.

Great question.

Thank you, Jason.

Jason will talk to you about <unk> and just to.

Give a quick answer for the hemophilia a program, yes, Pfizer reported this immediately to the regulatory authorities and happened at the same time as the clinical hold so has been with food although directly to the authorities for some period of time, so bettina over to you.

And good afternoon, everyone.

Thank you Sandy so thank you also for the question for Fabry. We're obviously very excited to have now the nine patients in the study and as far as those two patients who have come off the first one we had already announced at the World Conference in February . So this patient is being off.

Our financial results for this quarter are available in the press release issued this afternoon, which can be found on our website. This quarter, we continue to build on our 2021 investments, including advancement of our clinical programs, our preclinical research pipeline, and optimization of our in-house manufacturing capabilities.

We ended the quarter with approximately $400 million in cash, cash equivalents, and marketable security. We believe that our balance sheet remains strong for continued execution across our expected upcoming key categories.

Turning to 2022 full year guidance. Our 2022 full-year non-GAAP operating expenses continues to be expected to be between $280 million to $310 million for the year. This range excludes estimated non-cash stock-based compensation expense of approximately $40 million.

I'll now turn it back to Sandy for closing remarks.

We also expect to grow our investment in sickle cell disease in the second half of the year, following the transfer of the program back to Sangamo.

Thank you, Prathyusha.

When we last spoke in February, I said our accomplishments in 2021 would set us up for a strong 2022, and I believe our momentum in the first quarter bears this out. We are a fully integrated genomic medicine company building momentum with our novel science, clinical execution, and in-house manufacturing. The first quarter progress we have outlined demonstrates how this is coming together to create hope amongst the patients we're working to serve, a significant opportunity for our company and the potential for long term sustainable value for our shareholders.

I'm very grateful to my leadership team and all my Sangamo colleagues for their dedication to and hard work towards our mission of creating new transformational genomic medicines for patients.

We look forward to expected key milestones and catalysts throughout the year, including, presentation of additional Phase 1-2 STAR data for Fabry disease, as well as the dosing of patients in the expansion cohort.

Dosing of the remaining patients in our Phase 1 to Precision 1 study for sickle cell disease, along with presentation of additional data from the study.

Dosing of additional patients in our Phase 1-2 TX200 CAR-T reg steadfast study and Pfizer's potential resumption of the pivotal Phase 3 affine trial in haemophilia A.

Operator, please open the line for questions. As a reminder, to ask a question, please press star 1, your telephone, and to withdraw a question, please press the pound key.

Yes.

For months now.

Again, to ask a question, please press star one. It's also in keypad. And to withdraw a question, please press the pound.

The patient came off.

Towards the end of last year.

Please stand by while we compile the Q&A room.

On the.

Second patient came off.

Just a few weeks ago, so he's been in.

Our first question comes from the line of Yanan Zhu from Wells Fargo.

Hi, thanks for taking my questions and congrats on all the progress this quarter.

In terms of whether and when.

I have a few questions, but they're relatively quick ones.

The patients would resume.

Really we're looking at this together with the <unk> in terms of all the data coming out it's not just the biomarker because the clinical picture, it's a compensation.

On Fabry's program, sounds like two patients have been off ERT.

Right now there is no indication that.

<unk> would be necessary in either of these patients.

You mean, they don't need to go back onto ERP correct. Okay.

Congratulations on that finding and could you share the duration?

Thank you Bettina, Jason Jason can you help with some comments about the base editor.

for either both or the longer patients.

No you're very excited about it.

And also, what is the criteria for restarting ERT?

Yes, I'm happy to what is the specific question right. So yes.

Is it like a Lysol-GB3 level at baseline, or is it a specific Lysol-GBT level?

So we see that you have a abstract at TCT.

You have a zinc finger based.

Base editor.

And then on the HIM-B program, I have a very quick question, whether that case has been communicated with regulators.

Obviously with many many questions.

Much looking forward to the presentation such as questions such as how you enable the Nic case.

And then I have one question on the base editor.

Capability, there how you put everything into one vector, but I guess I'll just ask the kind of most.

Interesting question you my.

From my perspective that is.

With this.

<unk>.

I think our base.

With novel Architecture architecture.

Do you still have this phenomena by standard editing and how does that compare with the.

The base editor.

He is already out there.

Thank you.

Yes. So thank you for the question.

Yes.

We are.

<unk>.

A group of World class structural biologists and molecular biologist.

Sangamo team and we're continuously pushing to innovate our platform to develop new functionalities are.

Lots of great questions there.

Prior genomic medicines toolkit the.

So I'm going to distribute them here.

The latest one that we are presenting it as GCT as our base editor.

I think.

And so Bettina will take on the Fabry question.

For the really specific details it's best that you that you <unk>.

Engage with the scientists that are presenting the work and look at the work, but we're tremendously excited about it and I think what's most notable about it or one of the many notable things about the work that we're putting together is.

How because we're leveraging our zinc finger technology, we aren't able to construct a.

Jason will talk to you about base editors.

Compact based editor that we can deliver.

With an AAV.

Vector, which we think is pretty exciting but it can also be.

Used with other delivery modalities. So I think I think we've got something that.

Just another another tool in our kit and.

There are places where using base editors as particularly attractive, especially in multiplex editing of cells ex vivo, but there are other in vivo applications that we're excited about it.

Yes look I look forward to everyone being able to see the data and talk with our scientists and obviously we have a publication on this in the works and that will be another great time to learn more of the details.

And just to give a quick answer for the Haemophilia A programme.

Thanks, Jason just to be just to be clear.

<unk> construct to small if it can go into a single AAV it doesn't have to be broken up.

Other versions of this.

Yes, Pfizer reported this immediately to the regulatory authorities. And it happened about the same time as the clinical hold.

Periodic costs correct.

So it's been with all of the regulatory authorities for some period of time.

Great great. Thanks for the color.

So Bettina, over to you.

Our pleasure. Thank you for your questions.

Thank you, Sandy.

The next question comes from the line of Nicole <unk> from <unk> Securities.

So thank you also for the question for Fabry.

In the first quarter, Sangamo also had significant and trailblazing development on our wholly-owned TX200 CAR Treg cell therapy candidate for the prevention of immune-mediated rejection in HLA-A2 mismatched kidney transplantation from a living donor. On March 22, we dosed the first patient in our Phase I-II Steadfast Clinical Study in what we believe is the first-ever dosing of a human with a CAR Treg cell therapy candidate, continuing Sangamo's track record of advancing groundbreaking therapies in genomic medicine. The patient continues to do well following dosing with the autologous CAR Treg therapy, and has not reported any adverse events related to the treatment to date.

Thanks for taking my question.

We're obviously very excited to have now those nine patients in the study.

And as far as those two patients who have come off ERT, the first one we had already announced at the World Conference in February. So this patient has been off ERT for several months now. The patient came off ERT towards the end of last year.

Congrats on all the progress and given that earlier this week of vertex had a clinical hold on it may be that there are some questions that FDA has before the company can generate more data are you anticipating delays. Our question is from health authorities in Europe or from a slow.

And the the second patient came off ERT just a few weeks ago. So he's been off ERT.

And in terms of whether and when.

The patients would resume ERT.

Really, we are looking at this together with the PIs in terms of all the data coming out.

It's not just the biomarkers, the clinical picture.

It's a conversation.

Right now, there is no indication that ERT withdrawal would be necessary in either of these patients. You mean they don't need to go back on to ERT? Correct.

Okay.

During the dose escalation phase.

The setbacks program.

Thank you, Bettina.

And given that the company is a pioneer in the question I.

With this first in human study.

And higher poorly European sites on the clinical trials that go.

Will there be U S sites coming online in the near term.

Jason, can you help with some comments about the base editor?

Well can I can I hand, this one to roll our head of development who's been working very closely with.

I know you're very excited about it.

<unk> and Pfizer.

Yeah, I'm happy to.

I saw the vertex data and indeed, they had a clinical hold.

Cell therapy for diabetes.

What is the specific question?

We have been interacting regularly with regulators in Europe to ensure that we can proceed through our dose escalation for TX 200 without.

Right, so we see that you have an abstract at ASGCT, you have a zinc finger-based base editor.

Obviously, many, many questions, very much looking forward to the presentation, questions such as how you enable the NICASE capability there, how you put everything into one vector.

But I guess I'll just ask the most interesting question from my perspective, that is, with this kind of a...

They have zinc finger based, you know, totally novel architecture, architecture.

Through their ability to regulate the immune system, TX200 cells may protect the graft from immune-mediated rejection and reduce or eliminate the need for lifelong treatment with immunosuppressants.

In the steadfast clinical study design, each patient undergoes a leukapheresis procedure to collect their white blood cells, which after Treg cells are isolated, are genetically engineered, and then cryopreserved. The patient subsequently undergoes transplantation surgery to receive a kidney from a living donor. Following the recovery period, the patient receives their individualized TX200 investigational cell therapy. Dosing of patients therefore occurs several months after patient enrollment. Secondary objectives include the incidence of biopsy-confirmed acute graft rejection, incidence of chronic graft rejection, and confirmation that TX200 CAR-T reg cells localize to the transplanted kidney.

We also plan to evaluate the ability to reduce systemic immunosuppressive therapy, which carries the risk of significant systemic toxicity.

Annie <unk>.

Anticipated clinical is being placed on the program.

Sangamo expects to dose a second patient in the STEADFAST study around the middle of 2022 based on their transplant schedule and we plan to complete the first cohort which comprises a total of three patients by the end of the year.

We look forward to sharing data at the appropriate time.

We see the study as the first step in our R&D journey towards a potential pipeline of CAR Treg therapies for autoimmune diseases.

To answer that question I Hope does that answer your question with respect to that I think the key to that is regulatory interactions the whole way.

In addition to TX200, Sangamo is developing CAR Treg cell therapy candidates in preclinical studies, including for potential use in treating multiple sclerosis and inflammatory bowel disorders.

I will now turn the call over to our Chief Scientific Officer, Jason Fontenot, for an update on our preclinical programs.

Jason.

Got it.

What additional.

Break it down for me.

The other part of it was that.

Clinical trials that Gov, I only saw European sites clinical sites.

Are there going to be any U S site and the near term that are coming up.

Thank you, Rob, and good afternoon, everyone.

We have I think.

For the first.

The dose escalation, we're going to we're going to be it European sites. We have several sites that are signed on in.

We continue to make strong progress across a range of preclinical programs based on our cutting-edge genomic engineering platform.

Secondly, we will highlight important advances in our AAV capsid engineering program, a critical component of our CNS focus in vivo genome engineering portfolio.

Please see the press release we issued earlier this week, which is available on the Media and Investors page of our website.

We think we're going to be able to escalate.

These abstracts are representative of the robust Sangamo research engine and our continuous drive to innovate and evolve our genomic engineering platform.

I'm privileged to work with the dedicated team responsible for this, worked as the backbone of Sangamo's strong, long-term pipeline that we believe can deliver innovative medicines to patients.

Successfully this year.

Through our European colleagues.

Got it and then my quick follow up is just beyond renal transplant.

Congressionally required for car T. Reg therapy is in other chronic disease indications and other targets or exiting.

Well.

Pending on the cell therapy.

Pre conditioning is required for I think everything thats been its been.

Required preparation of the bone marrow to further <unk> I don't know of any examples where pre conditioning has not been used a number of pre.

Pre conditioning protocols, so theres constant work to reduce the patient burden with respect to that pre conditioning, but.

In order to ensure adequate grassman.

<unk>.

Typically these these arent being used.

Great. Thanks, so much.

Yeah.

Do you still have this phenomenon of bystander editing?

I will now turn the call over to Prathyusha for an overview of our financial results.

The next question comes from the line of looked at EC from RBC capital.

And how does that compare with the you know, the the the base editor that is already out?

Thank you, Jason, and good afternoon, everyone.

Oh, great. Thanks, so much for taking my question. Congrats on the progress I have two quick ones, maybe on Fabry, obviously very impressive serum biochemical response here, but wondering what the plan on actual kidney biopsy would you look at kidney biopsy directly in phase III or we look at them in the expansion cohort trial any calls.

We expect a significant portion of our operating expenses to be invested in continued progress of our LEAP programs, including February Phase III planning activities, Phase I-II activities for TX200, and preclinical work and CART, TREC, and CNS indications. We also expect to grow our investment in sickle cell disease in the second half of the year, following the transfer of the program back to Sangamo.

I'll now turn it back to Sandy for closing remarks.

Great and then maybe circling back on hemophilia, a just to be clear was the advent of deep vein thrombosis reported before or after the clinical hold was lifted it under award did the FDA alissa clinical whole fully aware of it as event or was that not the case. Thanks. So much.

Yeah.

Yeah, so thank you for the question.

Thank you, Prathyusha.

Thank you for your question so bettina taking.

Yeah, you know, we are, we have a group of world class structural biologists and molecular biologists on the Sangamo team, and we're continuously pushing to innovate our platform, to develop new functionalities for our genomic medicines toolkit.

The latest one that we're presenting at ASGCT is our base editor.

I'm very grateful to my leadership team and all my Sangamo colleagues for their dedication to and hard work towards our mission of creating new transformational genomic medicines for patients.

We look forward to expected key milestones and catalysts throughout the year, including, presentation of additional Phase 1-2 STAAR data for Fabry disease, as well as the dosing of patients in the expansion cohort.

Taking the questions for Fabry disease, So bettina please.

Dosing of the remaining patients in our Phase 1-2 Precision 1 study for sickle cell disease, along with presentation of additional data from this study, dosing of additional patients in our Phase 1-2 TX200 CAR-T reg steadfast study and Pfizer's potential resumption of the pivotal Phase 3 affine trial in haemophilia A.

I think, you know, for the really specific details, it's best that you, you know, engage with the scientists that are presenting the work and look at the work.

Operator, please open the line for questions.

But we're tremendously excited about it.

And I think what's most notable about it, or one of the many notable things about the work that we're putting together is how, because we're leveraging our zinc finger technology, we're able to construct a compact base editor that we can deliver with an AAV vector, which we think is pretty exciting.

Yes. So thank you for the question so as far as kidney biopsies are concerned we have now started doing kidney biopsies in the cohort four patients to cohort four patients that we have enrolled and dosed.

But it can also be used with other delivery modalities.

These are two naive patients and as such kidney biopsies.

Alright, good setting for.

For these patients and we will continue to do so in Naples, pseudo naive patients going forward, regardless of whether of which part of the study that added.

As a reminder, to ask a question, please press star 1, your telephone. And to withdraw a question, please press the pound key.

Thank you Bettina, Rob can you help us with the timing of the clinical hold and the DVT patients.

So, you know, I think we've got something that, you know, it's just another tool in our kit.

Again, to ask a question, please press star one. It's also in keypad. And to withdraw a question, please press the pound.

Yes, so just to.

And there are places where using base editors is particularly attractive, especially in the multiplex editing of cells ex vivo.

But there are other in vivo applications that we're excited about.

<unk>.

And, yeah, I look forward to everyone being able to see the data and talk with our scientists.

Please stand by while we compile the Q&A roll.

Set the timeline.

The Fraser Institute of voluntary Hall, and then this was followed shortly thereafter by a clinical hold by the FDA then the DVT occurred.

And obviously, we have a publication on this in the works.

Our first question comes from the line of Yanan Zhu from Wells Fargo.

And.

There was no additional regulatory response after the DVT.

<unk> disclosed that the patients had been enrolled in the trial. Despite a history of prior DVT, which would you be exclusionary normally but the clinical hold was lifted with that knowledge of DVT.

And Pfizer as we've announced his plan to resume the trial likely in the third quarter of 2022.

And that'll be another great time to learn more of the details.

Super helpful and if I may.

Why was that patient enrolled in the first place looks like that was a patient that was supposed to be excluded. So wondering if you have any any color on that thank you so much.

I don't have insight into that particular.

Protocol.

<unk>, but.

The patient the patient was indeed enrolled.

With knowledge of a prior DVT my understanding our understanding of this came after after all the events where were disclosed no.

You can be search and the investigators or no.

Reminded that they shouldnt and enrolled patients with previous history of DVT and I'm sure. The lethal will reflect this.

Once the drug is available in the market.

Got it thanks, so much guys Super helpful.

Thanks Jason.

The next question comes from the line of Ben Burnett from Stifel.

Just to be clear, the construct is small, it can go into a single AAV, it doesn't have to be broken up as other versions of this does. Correct. That's correct.

Hi, thanks for taking my questions and congrats on all the progress this quarter.

Hi, This is Kelly on for Ben Burnett.

Great, great.

I have a few questions, but they're relatively quick ones.

Thanks for taking our questions I.

Thanks for the cover.

And I guess really fast so maybe following up a little bit on prior question regarding the Fabry disease program can you give us a sense of the range of follow up time that the patients in the trial currently have.

Our pleasure.

Thank you for your questions.

On Fabry's program, sounds like two patients have been off ERT.

The next question comes from the line of Nicole Germino from TruWiz Security.

Congratulations on that finding and could you share the duration?

for either both or the longer patients.

And also, what is the criteria for restarting ERT?

Both the ones previously on <unk> and the ones who are naive and then maybe how much follow up time, we could expect to see at the update that.

Expected in the second half of 2022. Thank you.

Thanks for taking my question, and congrats on all the progress.

Certainly we're happy to do that can you give us some some color to that yes, absolutely. So.

Given that earlier this week, Vertex had a clinical hold, and it may be that there are some questions that FDA has before the company can generate more data.

Are you anticipating delays or questions from health authorities in Europe or from FDA during the dose escalation phase of the CEDDFAS program?

Is it like a Lysol-GB3 level at baseline, or is it a specific Lysol-GBT level?

We presented our <unk>.

<unk> data for the first few patients at wells this year.

And given that, you know, the company is a pioneer in the cardiac space with this first-in-human study, and I only see European sites on the clinical trials that does, will there be U.S. sites coming online in the near term?

And then on the HIM-B program, I have a very quick question, whether that case has been communicated with regulators.

And the patients the first patients were enrolled.

Approximately.

And I have one quick follow-up.

And then I have one question on the base editor.

More than it definitely more than a year ago. The first two or three patients are now in the follow up study, which means they are beyond one year follow up so.

Well, can I can I hand this one on to Rob, our Head of Development, who's been working very closely with our friends in Pfizer, Rob?

Thank you.

I saw the Vertex data and indeed they had a clinical hold that's a cell therapy for diabetes.

Up to around 15, or 18 months of follow up for the first patient.

We have been interacting regularly with regulators in Europe to ensure that we can proceed through our dose escalation for TX200 without any anticipated clinical holds being placed on the program.

Lots of great questions there.

To answer that question, I hope, does that answer your question with respect to that?

I think the key to that is regulatory interactions the whole way, um got it what what additional uh, Break it down for me.

And the the last two patients the patients enrolled in cohort four so for cohort four the last patient has.

Sure.

So I'm going to distribute them here.

Approximately four weeks I would say of follow up and we.

And so Bettina will take on the Fabry question.

<unk> paid.

Data for these nine patients in particular for the cohort for patients to be reviewed and upcoming safety monitoring Committee meeting.

And we.

Two then share data.

At an upcoming meeting likely in.

Early or later.

In this year.

The other part of it was, on clinicaltrials.gov, I only saw European sites, clinical sites.

And the thing that's been most impressive bettina has been sustained.

Are there going to be any U.S. sites in the near term that are coming online?

The.

We have, I think, for the first, for the dose escalation, we're going to be at European sites. We have several sites that are signed on, and we think we're going to be able to escalate successfully this year to our European colleagues.

The levels of Alpha Gal has been in both patients <unk> patients that are not near term.

Got it.

We're very pleased with the especially with the Alpha Gal enzyme activity level for these patients.

And then my quick follow up is, just beyond renal transplant, will conditioning be required for CAR Treg therapies and other chronic disease indications in either autologous or allogeneic settings?

Well, depending on the self-therapy, preconditioning is required for I think everything that's been that's been, I don't know of any examples where preconditioning has not been used.

Preconditioning Protocols.

So there's constant work to reduce the patient burden with respect to that preconditioning, but in order to ensure adequate engraftment, Typically, these are being used.

<unk>.

And in fact, the safety and Tolerability as we've.

<unk> gone through thoughtful.

Great, thanks so much.

Escalation processes team.

Very very comforting.

The next question comes from the line of Luca Issi from RBC Capital.

So we look forward to sharing all of that data later this year.

Oh great, thanks so much for taking my question, congrats on the progress, I have two quick ones.

Okay. Thank you very much.

You could also.

Just a quick question on the on the sickle cell disease program. I know you you dosed the first patient with an improved manufacturing method I was wondering if you could elaborate a little bit.

Exactly what those improved methods where at all.

No.

We havent been talking about that we are very pleased that our French incentive fee had been working on that for.

Maybe on Fabry, obviously very impressive serum biochemical response here, but wondering what's the plan on actual kidney biopsy?

For some period of time now and so this new patients as the new manufacturing method. So we're very careful that it's not a sufficient change to make this a new product but it.

It maximizes the chance of long term progenitors, which we think are essential.

For the for the <unk>.

Reduction of hemoglobin F and the prevention of.

Cycling events.

Would you look at kidney biopsy directly in phase 3, or would you look at them in the expansion cohort or trial?

Awesome. Thank you so much for that question.

Any call there would be great.

Next question comes from the line of Greg Harrison from Bank of America.

Hey, good afternoon, thanks for taking our question.

And sickle cell program.

And then maybe circling back on hemophilia A, just to be clear, was the event of deep vein thrombosis reported before or after the clinical hold was lifted?

What factors are driving your decision process on the future of this asset.

<unk> move forward, either on your own or with a new partner.

Where do you see the points of differentiation for your product.

Mark can you take this one.

In other words, did the FDA lift the clinical hold fully aware of this event, or was that not the case?

Sure.

Thanks so much.

Thank you for your questions.

Yes, so obviously, our first priority right now is to complete the phase one two precision trial.

Trying to get a sense of whether the new manufacturing process. Indeed has an effect on the clinical results.

Obviously, we're cognizant that.

Are there competitors, including CRISPR vertex our guiding in terms of when they are planning on filing.

We will basically take a look at the program if we feel it's competitive.

We will either advanced that ourselves or look for someone to advance the program with if we.

We feel that that.

Increases the likelihood that we would be able to get that to patients earlier.

One thing to keep in mind.

With sickle cell disease is that there is about 100000 patients in the United States of which 20% to 30000 are severe.

If you take a look at the ability to service patients with these so.

Personalized cell therapies effectively you're limited in terms of your ability to reach patients based on your manufacturing capacity and so we believe if we've got a competitive profile or if the data suggests we've got an improved profile and there is an opportunity to service that important.

Disease area and will provide the appropriate updates on our plans when we when we get there.

Great that's helpful. Thanks.

So Bettina is taking the questions for Fabry Disease.

The next question comes from the line of Gena Wang from Barclays.

So Bettina, please.

Hi, Good afternoon. This associate on for Gena. Thank you so much for taking our questions I had two on.

Yes.

So thank you for the question.

So as far as kidney biopsies are concerned, we have now started doing kidney biopsies in the cohort four patients, the two cohort four patients that we have enrolled in those.

These are two naive patients and as such, kidney biopsies are a good setting for, for these patients, and we will continue to do so in naïve or pseudo-naïve patients going forward, regardless of which part of the study that is in.

Thank you, Bettina.

So the first one again on the zinc finger architecture for high efficiency base editing.

Rob, can you help us with the timing of the clinical hold and the DPT patient?

I think in your abstract exploring deaminase domain from other bacterial toxins to improve performance and that one domain led to 60% as you think of human T cells. I was curious as to if you could disclose at this point, how many deaminase domains you explored and what was the general range of editing you observed.

And the second is a quick clarification.

For the car T program.

I'm steadfast there was a poster that you'll be presenting at CCT is this on trial design or can we see or are we going to see data from the first patient from your prepared remarks, I'm guessing not but just wanted to confirm thank you so much.

Uh, yes.

So, uh, just to, uh, set the timeline.

Jason will talk to you about base editors.

Hey, Jason just before we go to that Luis can you see it.

The Pfizer instituted a voluntary hold and then this was followed shortly thereafter by a clinical hold by the FDA.

Then the DVT occurred and there was no additional regulatory response after the DVT. We've disclosed that the patient had been enrolled in the trial despite a history of prior DVT, which would be exclusionary normally, but the clinical hold was lifted with that knowledge of a DVT and Pfizer, as we've announced, has planned to resume the trial likely in the third quarter of 2022.

<unk>.

Super helpful.

And just to give a quick answer for the Haemophilia A programme.

T Reg.

Yes, Pfizer reported this immediately to the regulatory authorities. And it happened about the same time as the clinical hold.

So it's been with all of the regulatory authorities for some period of time.

So steadfast in place that we will be presenting at S. GTT as a trial in progress poster, we will not be sharing any clinical data coming from that trial as GTT.

So Bettina, over to you.

Thank you, Sandy.

So thank you also for the question for Fabry.

We're obviously very excited to have now those nine patients in the study.

Jason Jason can you see something about <unk>. Please.

Yes.

On the question of the the different domains that we explored we explored.

A number of domains I would say.

Billy over 'twenty.

I'm not going to get into the details on that right now, but the team did an incredible job of.

Of mining.

Mining.

Proteome for four.

Potential M&A says and we've identified one that is particularly active and effective.

As a as a therapeutic so that's the one that we've moved forward and.

We believe it has all of the qualities necessary to deliver therapeutic grade base.

Base editing.

In the context of our zinc finger architecture, which we went over earlier allows us to design a base editing or is that it is highly compact.

Capable of being delivered by a single AAV.

And also obviously useful for ex vivo engineering.

Or any other delivery platform.

Great. Thank you so much.

Thank you for your questions.

The next question comes from the line of Maury Raycroft.

From Jefferies.

Hi, This is Kevin on for Maury.

Just a quick couple of questions first on the TX 200 patient could you say how that patient is doing and potentially whether you're getting any T. Reg persistent expansion.

And if I may, why was that patient enrolled in the first place?

The second patient came off ERT just a few weeks ago. So he's been off ERT.

It looks like that was a patient that was supposed to be excluded.

And in terms of whether and when.

The patients would resume ERT.

Really, we are looking at this together with the PIs in terms of all the data coming out.

And then could you talk more about.

It's not just the biomarkers, the clinical picture.

How often you're assessing blood biomarkers and what will drive your decision, making process to reduce immune suppressants.

It's a conversation.

Right now, there is no indication that ERT withdrawal would be necessary in either of these patients. You mean they don't need to go back on to ERT? Correct.

Okay.

There's very little I can say at the moment the patient is doing well.

We haven't given any indication yet when we're going to talk about the.

Thank you, Bettina.

Any biopsy data or any biomarker data.

Jason, can you help with some comments about the base editor?

It's early days in this in this study and we look forward to sharing the.

Alicia this year, probably more likely at the beginning of next year.

Okay. Great. Thanks, that's it that was actually my follow up if we could potentially see data.

By the end of this year and what might be included in that data update and then if you could talk about what guiding your.

I know you're very excited about it.

Yeah, I'm happy to.

So wondering if you have any, any color on that.

What is the specific question?

So T V D. How much follow up do you need from cohort Korean cohort four and do you need a biopsy data from cohort for them to make that final determination of what is going into the expansion cohort.

Tina could you do absolutely. Thank you sandy so.

Thank you.

Right, so we see that you have an abstract at ASGCT, you have a ZincFinger-based base editor.

Obviously, many, many questions, very much looking forward to the presentation, questions such as how you enable the NICASE capability there, how you put everything into one vector.

Four is our final cohort for the dosage escalation phase we have those cohort four at five 813, the protocol uhm allowed for us to reach this does.

But I guess I'll just ask the most interesting question from my perspective, that is, with this kind of a...

That was based on the safety and Tolerability profile.

As I mentioned earlier, we will be holding and safety monitoring Committee meeting this will be held by Q3 and at that point in time all of the data that we have up until that point will be used to assess our next steps into the best way.

Forward for our <unk>, our our expansion phase and we intend to those patients and the expansion phase as soon as we help we.

As we gather the safety monitoring committee and make that decision to move forward. So there won't be any biopsy data, we only have baseline biopsy data at this point in time full cohort four and the data will be based on safety tolerability and by marketed.

Okay.

<unk>.

We've been very lucky we've been very lucky to have efficacy from the first tours and this and across each one of the doses. So where it's it's an important decision to make it will be based understanding the total ability maximizing the chance of <unk> [noise].

What kind of points quite the biopsies are you going to look at.

We look at baseline in six months.

And so you can expect that we won't have any biopsy database here will will have to biopsy data likely uhm towards the two share towards the beginning of next year.

Got it and when do you plan on taking two N C. All the way up to commercial product do you expect to enter the extension cohort with commercial grade product or will that before.

Separate cup at all.

So we are we are in plan and plans to transition to the commercial manufacturing, but we're not guiding on which which we're gonna use for the expansion cohort right now but.

But obviously, where it becomes very important for us is to make sure that we've got the commercial.

Production facility ready for enrolling the phase III program and.

That way, we've got a consistent phase III commercialization months.

Got it and and I'm, hoping that two procession <unk> program 50 M. C. You did mention that phase III readiness.

Activities are in progress and you've got the <unk> transfer from Santa fee occurring with their optimize program.

When all of that is said and done will you be at commercial grade product for.

The S T D programmer therapy for their work to be done.

So we we expect to do the tech transfer M. B phase three Reddy as part of the preparation for the phase III plan.

And today's three would be run with commercial product correct.

Correct.

Great. Thanks for taking our questions.

Thank you.

The next question comes from the liner Patrick <unk> from each billing right.

Thanks, Good afternoon, I just have a few follow up questions action on our car to your Red platform. So first I'm wondering if you can discuss the status of the preclinical Carcieri Rag cell therapy program, specifically, an Ivy D and M S and what the timeline to an I M. B R. C. K filings look like for those programs.

And then separately what learning if any have emerged so far from the tea extra under program that could impact the IBD and M. S programs.

So I'm gonna ask Jason to to tell you about his passion for T. Rex in the workplace done by our colleagues in <unk>. We we've only just do as the first two right patient. So there is no new learnings yet that we can apply.

To be out there.

Programs and we haven't <unk> on the timing so Jason <unk> can you give us some indication of the progress that you're seeing on T rank programs.

Yeah. Thanks, Sandi, yeah. So we have we have very active preclinical.

Preclinical programs.

For developing Carty regs for both IBD and multiple sclerosis, we've disclosed that one one of the car targets for the IBD programs as I'll twenty-three receptor and I believe that there was a poster presented on that topic.

In in at a conference in Europe recently, so I I would point you to to that poster airport for details on the program.

For the multiple sclerosis program, we have disclosed a car targeting.

MOG.

Protein that's restricted to the CNS and work is proceeding on both of those preclinical work is proceeding on both of those programs we built a.

Great kind of engine to to evaluate to to generate and evaluate cars through a in vitro and in vivo screening funnel. So that we have the optimal car. That's designed specifically for for working and regulatory T cells.

So that work is well underway and we are now evaluating our car engineered T regs in vivo models and both of those indications and we're really excited about the work that we've done and and the the platform that we put in place and.

And it's true that while we haven't learned anything from the patient instead of a dose with TX 200, I will point out that the investments that we've made.

Process development and manufacturing as well as obviously the biological expertise of of the team that's working on this.

For all developed during the TX 200 <unk>.

Clinical efforts end up all up to this day and all of that information is obviously feeding into both of those preclinical programs.

Very excited about about our progress and then the last thing I'll point out is that the other area that were.

Really invested in his leveraging our zinc finger.

Genome engineering platform to develop allogeneic T regs, and we're doing that by both doing.

Doing engineering of T. Rex derived from healthy donors. So the so called healthy donor route two autologous cell therapies, but we're also doing a lot of work to derive a T. Rex from Ips's sees such that we can engineer induced pluripotent stem cells to be allogeneic and have.

Kind of continuous perpetual source of T. Rex for an off the shelf therapy. So we've got a really active.

<unk> program platform program at the company and tremendous advance and getting the first patient dose and we look forward to tell you more about the latest developments when it's appropriate.

Nope, that's really helpful. Thanks, so much.

Yeah, and your questions at this time and I'll try not to call back to you okay.

Thank you once again for joining us today and for your questions. We look forward to keep you updated on our future developments.

This concludes today's conference call. Thank you for participating he may now disconnect.

[music].

I don't have insight into that particular protocol, violation, but the patient was indeed enrolled with knowledge of a prior DVT.

Zink's finger-based, totally novel architecture, do you still have this phenomenon of bystander editing?

Thank you for standing by and welcome to the Sangamo first quarter 2020 do teleconference call. At this time all participants lines are in listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During the session you will need a restaurant on your telephone. Please be advised that today's conference is being recorded if you require any further.

My understanding, our understanding of this came after all the events were disclosed.

And how does that compare with the base editor that is already out there?

At this time, please press star Zero I would now like to hand, the conference over to your speaker today, Mr. Louis Wilkie. Thank you. Please go ahead.

And you can be certain that the investigators are now reminded that they shouldn't enroll patients with previous history of DVTs, and I'm sure the label will reflect this once a drug is available on the market.

Yeah, so thank you for the question.

Got it.

Good afternoon, and thank you for joining us today with me on the call. This afternoon, Sandy Macrae, Chief Executive Officer, Mark Mcclung, Chief Operating Officer, Patricia Barber, Chief Financial Officer, Jason <unk>, Chief Scientific Officer, Rob shops haven't had the development.

Ciena Cockrell, Chief Medical Officer lots.

The latest one that we're presenting at ASGCT is our base editor.

Lots more corporate presentation can be found at our website Banco my dot com under the investors and media section of the events and presentation page.

This call includes forward looking statements regarding Sangamo current expectations. These statements include but are not limited to statements related to the therapeutic and commercial potential of our product candidates the anticipated plans and timelines for Sangamo and our collaborators for initiating in conducting clinical trials in presenting clinical data.

Execution of our corporate strategy advancement of our product candidates.

22 financial guidance and other statements that are not historical facts.

Actual results may differ materially from what we discuss today.

These statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC.

On a quarterly report on Form 10-Q for the fiscal quarter ended March 31 2022.

Annual report on Form 10-K for the fiscal year ended December 31 2021.

The forward looking statements stated today are made as of the sites and we undertake no duty to update such information, except as required by law.

It's cool we discuss a non-GAAP operating expenses reconciliation of this measure to our GAAP operating expenses can be found in today's press release, which is available on our website.

Thanks so much, guys.

I think, you know, for the really specific details, it's best that you, you know, engage with the scientists that are presenting the work and look at the work.

Now I'd like to turn the call over to our CEO .

Sandy Macrae, Thank you Luis and good afternoon to everyone on Nicole.

Super helpful.

But we're tremendously excited about it.

Building on a year of significant clinical and preclinical progress in 2021 <unk>.

The next question comes from the line of Ben Burnett from Stiefel.

<unk> advanced multiple programs in the first quarter of 2022, as we continue our mission to create transformative genomic medicines for patients using our innovative technologies.

Hi, this is Kaylee Brizon for Ben Burnett.

But it can also be used with other delivery modalities.

Thanks for taking our questions.

We are proud to have three programs progressing towards or in late stage development and to be the first company known to us to dose a patient in what we believe is a completely new treatment modality.

I guess really fast, this may be following up a little bit on prior question, but regarding the Fabry disease program, can you give us a sense of the range of follow-up time that the patients in the trial currently have, including both the ones previously on ERT and the ones who were naive, and then maybe how much follow-up time we could expect to see at the update that's expected in the second half of 2022?

This quarter, we do have three additional patients and are differentiated and wholly owned gene therapy program for the treatment of adults with fabry disease.

Thank you.

We have now successfully dose or two of the nine patients across four cohorts and the STAAR study just to complete the dose escalation portion of the phase one two study.

We're delighted to have achieved this significant milestone was.

With recent changes in the competitive landscape.

We believe that we are in a leading position amongst gene therapies are fabry disease.

We look forward to presenting updated data in the second half of 'twenty two.

Certainly, we're happy to do that.

We incentive fee dose a patient in the phase one two precision one study.

Bettina, can you give some color to that?

Finger nucleus modified to totally this cell therapy for the treatment of sickle cell disease.

Yes, absolutely.

We expect to complete patient dosing in the third quarter of 2022.

And look forward to sharing an update on data in the second half of this year.

Regarding the phase III hemophilia, a gene therapy trial, Pfizer announced in March the FDA lifted the clinical hold that have been pleased when they are finding trial.

Pfizer noticed that dosing will resume once all necessary conditions are met including approval of updated trial protocols by regulatory authorities.

Pfizer anticipate resuming the trial in the third quarter of 2002 with a pivotal data readout estimates in the second half of 2023.

So we presented our Fabry data for the first, few patients at World this year. And the patient, the first patient were enrolled approximately Definitely more than a year ago, the first two or three patients are now in the follow-up study, which means they are beyond one year of follow-up, so up to around 15 or 18 months of follow-up for the first patient.

In March <unk> dosed, the first patient in our phase one two steadfast clinical study evaluating TX 200, our wholly owned just totally this car T. Reg cell therapy product candidate for the prevention of immune mediated rejection and easily <unk> mismatched kidney transplantation from a living donor.

And the last two patients are the patients enrolled in cohort four.

We are thrilled to have achieved this momentous milestone, which you believe is the first in human dosing of an engineered car T Reg cell therapy candidate.

So for cohort four, the last patient had approximately four weeks, I would say, of follow-up and we, anticipate that data for these nine patients, in particular for the cohort four patients, to be reviewed at an upcoming safety monitoring committee meeting.

Most importantly, the patient continues to be well.

And has not reported any adverse events related to the treatment to date.

We are planning to dose the second patient in the steadfast study around the middle of 'twenty two.

And Theyre transplants schedule I'm looking forward to sharing the appropriate data at the right time.

So, you know, I think we've got something that, you know, it's just another tool in our kit.

Before providing more details on these programs I want to note. These advancements have resulted from our strategic and focused use of research and development capabilities, which are supported by our in house infrastructure, including AAV and cell therapy manufacturing facilities.

We believe that this positions us well to create new transformative medicines for patients in need and to generate long term value for our.

Shareholders.

And we plan to then share data at an upcoming meeting likely in early or later in this year.

With that I'd like to head over turnover the call to our head of development rope short too.

I would tell you in the progress of our clinical programs in more detail.

And the thing that's been most impressive, Bettina, has been how sustained the levels of alpha-gal have been in both patients on ERT and patients that are not on ERT.

And there are places where using base editors is particularly attractive, especially in the multiplex editing of cells ex vivo.

You Sandy and good afternoon to everyone on the call.

But there are other in vivo applications that we're excited about.

Our development organization remains focused on execution in the clinic and we are pleased with this quarter's progress beginning with our phase one two star study examining as Rob the genes that are <unk> or <unk>, which is our wholly owned gene therapy program for the treatment of fabry disease in adults.

And, yeah, I look forward to everyone being able to see the data and talk with our scientists.

Exactly.

And obviously, we have a publication on this in the works.

We're very pleased with the, especially with the alpha-gal enzyme activity levels for these patients.

And that'll be another great time to learn more of the details.

And in fact, the safety and tolerability as we've gone through with this thoughtful dose escalation process has been very, very comforting.

Thanks, Jason.

This quarter the safety monitoring committee approved escalating to a fourth dose cohort as outlined in the STAAR study protocol.

And so we look forward to sharing all of that data later this year.

This was based on the totality of data from the previously dose patients.

Okay, thank you so much.

Two patients have since been dosed in cohort four at the five E. <unk> vector genomes per kilogram dose level completing the dose escalation portion of this phase <unk> study.

If you could also, just a quick question on the sickle cell disease program.

Furthermore, this quarter, we dosed an additional patient in cohort three this achieved the total of three patients in this cohort and nine patients overall that had been dosed in the STAAR study to date.

In addition, during this quarter, we completed withdraw of enzyme replacement therapy from a second patient, which means that we now have withdrawn one each from the first and second cohorts. These patients are being closely monitored and investigators have thus far not deemed it necessary to resume enzyme replacement therapy we.

Spec to provide updated results from the STAAR study in the second half of 2022 and are actively preparing for both the phase two expansion cohorts in a phase III clinical trials.

I know you you dosed the fifth patient with an improved manufacturing method.

In the phase one two precision one study of SAR 45136 for the treatment of sickle cell disease. This quarter, we dosed. The first patient. This patient was the first in the study to receive a product candidate manufactured using improved methods that have been shown in internal experiments to increase the number of long.

I was wondering if you could elaborate a little bit exactly what those improved methods were at all.

Term progenitor cells in the final product mix.

Back to dose the remaining patients in this study in the third quarter of this year, we look forward to sharing an update on the precision one study in the second half of 2022.

Feedback has been received from the FDA in phase III, enabling activities, including manufacturing readiness are in progress.

The orderly transition of Sanofi has rights and obligations under this program back to Sangamo is progressing well and is on track to be completed on June 28.

As previously outlined Sangamo is excited to have this asset back in our hands soon.

Thank you.

Just to be clear, the construct is small enough that it can go into a single AAV. It doesn't have to be broken up as other versions of this does. Correct. That's correct.

As sandy outlined in his opening Pfizer recently announced that in March of this year. The FDA lifted its clinical hold on the phase III find trial evaluating evaluating <unk> <unk>, an investigational gene therapy for hemophilia a.

We haven't been talking about that.

Great, great.

We're very pleased that our friends at Sanofi had been working on that for some period of time now.

Thanks for the cover.

And so this new patient is the new manufacturing method.

Our pleasure.

So we're very careful that it's not a sufficient change to make it a new product.

Thank you for your questions.

But it maximizes the chance of long-term progenitors, which we think are essential for the engraftment and the production of hemoglobin F and the prevention of sickling events.

It was put in place following the observance of factor eight expression levels greater than 150% in some treated participants.

Awesome, thank you so much for that question.

The next question comes from the line of Nicole Germino from TruWiz Security.

Next question comes from the line of Greg Harrison from Bank of America.

Thanks for taking my question and congrats on all the progress.

Given that earlier this week Vertex had a clinical hold and it may be that there are some questions that FDA has before the company can generate more data.

Pfizer has announced that the voluntary pause remains in place until all necessary conditions are met including approval of an updated trial protocols by regulatory authorities.

In addition, Pfizer was made aware of a below the knee deep venous thrombosis in one participant with elevated factor eight levels. This patient had a history of thrombotic events prior to participation in the trial, which is a known risk factor for subsequent events and an exclusion criterion for participation in the <unk> trial.

The case was the SaaS to understand all potential contributing factors, including Miss doses of investigator prescribed direct oral anti coagulant. The patient is reported to be doing well.

What factors are driving your decision process on the future of this asset as you move forward, either on your own or with a new partner?

Are you anticipating delays or questions from health authorities in Europe or from FDA during the dose escalation phase of the CEDDFAS program?

Pfizer and Sangamo remained committed to the hemophilia community and Pfizer anticipate resuming the trial in the third quarter of 2022 with a pivotal data readout estimated in the second half of 2023.

In the first quarter and Sangamo also had significant and Trailblazing development and our wholly on TX 200 car T. Reg cell therapy candidate for the prevention of immune mediated rejection in HLA <unk> mismatch kidney transplantation from a living donor on March 22nd we dust.

Where do you see the points of differentiation for your product?

And given that, you know, the company is a pioneer in the cardiac space with this first in human studies, and I only see European sites on the clinical trials that does, will there be U.S. sites coming online in the near term?

Our first patient in our phase one two steadfast clinical study and what we believe is the first ever dosing of a human with a car T Reg cell therapy candidate.

Mark, can you take this one?

And I have one quick follow up.

Continuing <unk> track record of advancing groundbreaking ceremony of therapies and genomic medicine.