Q3 2019 Earnings Call

Good afternoon, and welcome to the Sangamo Therapeutics teleconference to this stuff third quarter 2019 for natural resource.

This call is being recorded.

Operator: This event is being recorded. I will now pass you over to the coordinator of this event, MacDavid Stilwell, Senior Vice President of Corporate Communications and Investor Relations. You may begin.

I would now pass you over to the coordinator of this event Mcdavid Stilwell Senior Vice President Corporate Communications and Investor Relations you may begin.

Hello, and thank you for joining us.

MacDavid Stilwell: Hello, and thank you for joining us. As we begin, I'd like to point out that we've posted our updated corporate presentation on our website, and we'll be referencing several of those slides today. A link to the slide presentation may be found on our website, sangamo.com, on the events and presentations page of the investors and media section of the site. I'd also like to remind everyone that the projections and forward-looking statements that we will discuss during today's conference call are based on the information that we have available today. Forward-looking statements include, but are not limited to, statements related to the timing and scope of Sangamo's genomic medicine platform and products, the potential for Sangamo's product candidates to provide clinical benefit to patients, its development and manufacturing plans, and its expectations regarding its financial performance. Actual results may differ substantially from what we discussed today, and no one should assume at a later date that our comments from today are still valid.

As we begin I'd like to point out that we posted our updated corporate presentation to our website.

We'll be referencing several of those slides today.

A link to the slide presentation may be found on our website Sangamo dot com.

The events and presentations page of the investors and media section of the site.

I'd also like to remind everyone that the projections and forward looking statements that we will discuss during today's conference call or based upon the information that we have available today.

Forward looking statements include but are not limited to statements related to the timing in scope of San Dimas genomic medicine platform.

And products the potential for second proposed product candidates to provide clinical benefit to patients.

Thank you most development and manufacturing plans and second most expectations regarding its financial performance.

Actual results may differ substantially from what we discussed today no one should assume at a later date or comments from today are still Dallas.

These forward looking statements are not guarantees of future performance and are subject to risks and uncertainties and assumptions that are detailed in documents with the company files with the Securities Exchange Commission.

MacDavid Stilwell: These forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties and assumptions that are detailed in documents that the company files with the Securities and Exchange Commission, specifically in our most recent annual report on Form 10-K and in our most recent quarterly report on Form 10-Q. The forward-looking statements stated today are made as of this date, and Sangamo undertakes no duty to update such information, except as required under applicable law. With me this afternoon on this call are several members of the Sangamo senior management team, including Sandy Macrae, Chief Executive Officer. The newest member of our executive leadership team, Sung Lee, Chief Financial Officer; Stephane Boissel, Head of Corporate Strategy; Adrienne Wolfson, Head of Research and Development; Bettina Cockroft, Chief Medical Officer; and Gary Loeb, General Counsel. And again, during this call, we'll refer to several slides in our corporate presentation. And those slides may be found on the events and presentations page of the investors and media section of our website.

Specifically in our most recent annual report on Form 10-K and in our most recent quarterly report on Form 10-Q .

The forward looking statements state or today are made as of this date and thinking about undertakes no duty to update such information, except as required under applicable law.

With me this afternoon on this call or several members of the segment senior management team.

I think Sandy Mcrae, Chief Executive Officer.

It was a member of our executive leadership team sung Lee Chief Financial Officer.

Bump also had a corporate strategy.

It really looks and research and development.

Bettina Cockroft, Chief Medical officer, and carry lower General counsel.

And again during this call will refer to several slides in our corporate presentation and those slides may be found on the events and presentations page of the investors and media section of our website and now I'll turn the call number to sandy.

Alexander D. Macrae: And now, I'll turn the call over to Sandy.

Alexander D. Macrae: Thank you, McDavid, and good afternoon to everyone on the call. Thank you for joining us. At Sangamo, our mission is to translate our groundbreaking science into genomic medicines that transform patients' lives. We are realizing this vision by developing capabilities that allow us to design therapeutic approaches to resolve the underlying genetic causes of disease, using whatever technology is best suited to deliver that treatment, including gene therapy, ex-vibo gene-edited cell therapy, in-vibo genome editing, and In People Gene Regulation. As we move ahead with a robust pipeline of genomic medicines across these various platforms, we understand that investors would like further insights into the many programs that are helping to define the future of Sangamo. Accordingly, we would like to share how we prioritise drug development and research targets, as well as the strategy that we use to help realize the full potential of our suite of technologies through our partner programs and wholly owned pipelines. We plan to cover all these topics and more at Sangamo's R&D Day on Tuesday, December 17th in New York City.

Thank you make David and good afternoon, everyone on the call. Thank you for joining us.

I just think among our mission is to complete our groundbreaking science into genomic medicines the transformed patients flies.

We are realizing this vision by developing capabilities the allow us to design to therapeutic approaches to so the underlying genetic causes of disease.

Using for ever technology is best suited to deliver that treatment, including gene therapy.

Makes people gene edited cell therapy.

In people genome editing.

And in people gene regulation.

As we move ahead with a robust pipeline that you know with made since of course. These theories platforms. We understand investors would like further insights into the many programs are helping to define the future of saying.

Accordingly, we would like to sheer how do we proto-stirrup development in research targets I suppose the strategies that we utilize to help related to potential for suite of technologies through or partner programs, an Julio pipeline.

We plan to cover all these topics and more sanguine R&D on Tuesday December 17th in New York City.

Over the past two years, a newly older vessels with the organization single has transformed into a fully integrated clinical stage biotech company.

Alexander D. Macrae: Over the past three years, and at nearly all levels of the organization, Sangamo has transformed into a fully integrated clinical stage biotech company. The capabilities we have developed allow us to move our growing pipeline of product candidates forward from the research labs, through preclinical development, into the clinic, where we're now driving studies forward and delivering clinical results one study at a time. R&D today will provide an opportunity to pursue an in-depth look at the technological, clinical, and organizational revolution and evolution that has taken place at Sangamo and to demonstrate what makes us a truly unique and innovative genomic medicine. Numerous speakers from across the company, including our leadership team and some of our lead scientists, will present their work and be available to take your questions. This will be our first public presentation following posters at the American Society of Haematology Annual Meeting, or ASH, showing updated clinical data for programs currently in the clinic, follow-up gene therapy data for SV525 for haemophilia A, and preliminary ex vivo gene-editing cell therapy data for ST400 in beta thalassemia.

Capabilities, we have developed a loose to be for growing pipeline of product candidates forward from the research labs to preclinical development into the clinic, we were no trying things somebody's forwards and delivering clinical results one study into Tony.

Aren't DC will provide an opportunity to pursue or an index fluke or the technological clinical an organizational resolution and solution has taken polices sangamo and to demonstrate what makes it was a truly unique and innovative do you know we've made some companies.

Numerous speakers from across the company, including our leadership team in some of our lead selling to will present their work and be able to take your questions.

This would be a first public presentation pulling the posters at the American Society of Hematology annual meeting ash showing updated clinical data for programs currently in the clinic <unk>.

<unk> gene therapy due to for SP five to fight for hemophilia, a and preliminary ex vivo gene edited cell therapy to various T 400, it'd be to tell the C media.

Alexander D. Macrae: We look forward to discussing the progress we've made in these programs. We will also show how insights from our most advanced programs are being incorporated into the next wave of programs that we're pulling forward for clinical development in rare diseases, autoimmunity, and CNS therapeutic areas. Furthermore, we will provide an overview of our long-term strategy to advance our pipeline of genomic medicines, both in partnership with pharmaceutical companies and as programs wholly owned by Sangamo. Before I turn to the call, and turn the call over to the team, to discuss recent business and financial highlights, I'd like to introduce two new members of leadership at Sangamo. The first is Bettina Cockroft, who recently joined Sangamo as its Chief Medical Officer. Dr. Cockroft oversees all the clinical development activities and operations and reports to Adrian Wolfson, our Head of R&D. Bettina brings over 20 years of clinical development experience across multiple therapeutic areas and in several countries.

We look forward to discussing the progress we've made in these programs.

We will also show incentives insights from our most advanced programs are being incorporated into next week programs that were pulling forward to clinical development in rare diseases autoimmunity CNS therapeutic areas.

Further we will provide an overview for long term strategy due to advance our pipeline of genomic mentions booked in partnership with pharmaceutical companies.

As programs wholly owned by saying.

Before I turn to the coal.

Turning to co to the team to discuss recent business and financial highlights I'd like to introduced two new members of leadership is saying.

First just Bettina Cockrell, who recently joined signed them was chief Medical Officer, Dr. corn crop overseas older clinical development activities and operations and reports to 18 moves and or head of R&D.

Bettina brings over 20 years of clinical development experience across multiple therapeutic areas and in several countries.

Alexander D. Macrae: With a steady flow of readouts from her ongoing clinical studies and the initiation of additional trials in the very near future, we are delighted to have her here and look forward to her contributions. We believe she will be a key player in helping us realize our mission. Second, we have Sung Lee, our new Chief Financial Officer. Sung oversees finance, facilities, and information technology functions for Sangamo.

Steady fluid returns from are ongoing clinical studies and the initiation of additional trials in the very near future were to lunch to to hover here and look forward to her contributions. We believe she will be a key player in helping us we'd like sort of mission.

Second to some lead our new Chief Financial Officer, some overseas finance facilities information technology functions for saying.

Alexander D. Macrae: He joins us from Gilead, where he spent nearly 14 years, most recently as Senior Vice President leading the Financial Planning and Analysis and Investor Relations function. His exceptional track record of improving operational performance, leading large teams, and communicating with investors, as well as his deep experience and success in financial planning and analysis, will have a significant impact on Sangamo as we continue to grow. We're very pleased to have both these talented leaders join us. Lastly, I want to acknowledge the promotion this quarter of Andrew Bramall-Meyer to Executive Vice President of Technical Operations. His position on the leadership team highlights the importance of manufacturing and operations for Sangamo in advancing our pipeline forward. We look forward to Andy's continuing contributions in this much-deserved leadership role. I'll now pass the call over to Adrian, who will discuss the ASH abstracts which were posted online this morning.

He joins us from Gilliand, we spent nearly 14 years, most recently as senior Vice President, leading the financial planning and analysis and Investor relations functions.

His exceptional track record of improving operational performance, leading launch teams and communicating with investors as well as his deep experience in success in financial planning and analysis will have a significant impact on sustainable as we continue to grow.

We're very pleased to put these talented leaders join us.

Lastly, I want to acknowledge the promotion this quarter with undue braemar to executive Vice President of technical operations.

His position leadership team highlights importance of manufacturing in operation for sank and advancing our pipeline forward.

We look forward time these continuing contributions in this much deserved leadership.

I'll now pass the co over to Adrian who will discuss the ash abstracts, which posted online this morning.

Thank you Sandy and good afternoon.

This morning, the American Society of Hematology posted several abstracts on their website I would like to highlight the softening.

This would be shun as posters at their annual conference in Orlando, Florida next month and include data from our SP five to five hemophilia Ray gene therapy clinical program and also a rest T 400 ex vivo gene edited cell therapy program for pizza to other senior.

Adrian: Thank you, Sandy, and good afternoon. This morning, the American Society of Haematology posted several abstracts on their website that I would like to highlight this afternoon. These will be shown as posters at their annual conference in Orlando, Florida, next month and include data from our SB525 Haemophilia Array Gene Therapy Clinical Program and also our ST400 Ex vivo Gene Edited Cell Therapy Program for beta thalassemia. I would now like to provide some more context on what you should expect to see in those posters and our perspective on the abstract data.

Well now like to provide some more context, what you should expect to see in those posters and they'll perspective on the abstract data.

Please note due to the ash embargo rules will not be able to discuss the data at this time beyond the scope of what was shown in the abstracts that were published this morning.

The ups trucks, we submitted in early August .

First I'd like to discuss SP five to five well hemophilia Ray gene therapy candidates, which is partnered with Pfizer.

The poster at US will contain updated patient follow up data from the old to study the phase one to open label dose ranging study in adult patients with severe hemophilia Ray.

Adrian: Please note that, due to the ASH embargo rules, we will not be able to discuss the data at this time beyond the scope of what was shown in the abstracts that were published this morning. The abstracts were submitted in early August. First, I'd like to discuss SB525, our Haemophilia A gene therapy candidate, which is partnered with Pfizer. The poster at ASH will contain updated patient follow-up data from the AUTUS study, a Phase 1-2 open-label, dose-ranging study in adult patients with severe haemophilia A. You will recall that our last data follow-up was at ISTH in July 2019, where we showed data from the first four subjects at the high dose, 3E13, the furthest along of whom had been followed for 24 weeks.

You will recall that our law states a follow up with I.S.G.H. in July 2019, where we show data from the first four subjects at the high does 313.

Furthest along with him at being followed for 24 weeks.

Oh, My Gosh, we would have updated data analyses, including facts rate levels bleeding rates and fight to usage for all five there's a high dose patients with follow up ranging from approximately four to 11 months.

We continue to believe the data published in the abstract presented there were presented at ash, including the observed rapid kinetics durability of the response is thus far and they're relatively low intra cohort variability as well as the cessation that bleeding events and the elimination of exogenous factor.

Adrian: At ASH, we will have updated data and analyses including factor eight levels, bleeding rates, and factor usage for all five of the high-dose patients with follow-up ranging from approximately four to eleven months. We continue to believe that the data published in the abstract presented at ASH, including the observed rapid kinetics, durability of the responses thus far, and the relatively low intra-cohort variability, as well as the cessation of bleeding events and the elimination of exogenous factor replacement use, together suggest that we may have a differentiated mechanism. As of the August 3rd ASH abstract submission date, of the 5 patients treated in the highest dose cohort, 3 patients None of these patients experienced a loss of factor VIII activity levels, and no new serious adverse events were reported. As a reminder, patients in the ALTAR study were not treated with prophylactic steroids. We look forward to showing the most up-to-date data at the ASH poster presentation.

Replacement news together suggest that we may have a differentiated hemophilia raging therapy product with the potential to deliver significant benefit to patients.

As a fuel because size ash abstract submission date.

Five patients treated in the highest dose cohorts three patients who have followed for at least eight weeks experience transients mild grade one LTL innovations and were treated with corticosteroids. None of these patients experienced a loss of French rates activity levels and no new serious adverse events will report.

Good.

As a reminder, patients in the old to study were not treated with prophylactic steroids.

We look forward to showing them I stop today data at the Ash poster presentation.

Moving on now two S T 400, or ex vivo gene edited cell therapy for Pizza, Tom a senior.

That's the 400, there's an autologous cell therapy product candidate that involves the editing the patients I'm genes.

Adrian: Moving on now to SG400, our ex vivo gene-edited cell therapy for beta thalassemia. ST400 is an autologous cell therapy product candidate that involves the editing of the patient's own genes, editing the genes in a patient's own hemopoietic stem cells using non-viral delivery of zinc finger nuclease technology. In the Phase 1-2 study, ST400 is being evaluated in patients with transfusion-dependent beta-thalassemia. In pre-clinical studies, zinc finger nuclease mediated disrupts the Gatter Binding Region with the intronic erythroids, arystoid-specific enhancements. BCL11A increased endogenous fetal hemoglobin production in erythroid cells while also allowing healthy multilineage hemopatoiesis. As shown on slide 24 of the corporate deck, for ST400, cells are apheresed from the patient, edited to knock out the erythroid-specific enhancer of the BCL11A repressor gene, harvested, and then infused back into the patient following myelob If you look at slide 26, you can see examples of the various mutations that may lead to beta thalassemia.

Seem to genes and patients own hema plastic stem cells, using non viral delivery everything from getting face technology.

In the phase one two study S. T 400 is being evaluated in patients with transfusion dependent beta thalassemia.

In preclinical studies in finger Nucleases mediated disruption at the gas a binding region refi and tronic resorts.

The risks where its specific in homes.

[noise] Bcl M&A increased unfortunately people hemoglobin production and the risk reward cells, while also allowing healthy mostly lineage remember two recess.

The southern shown on slide 24 of the corporate Guy Foresi 400 sells the rate for reasons from the patient attitude to knock out the a record specific enhance the theater left a neighbor presaging harvested and infuse back into the patient falling Milo place if conditioning it through self fund.

If you could slide 26, you can see examples of the ferrous mutations that may lead to Peter Thomas seem yeah.

The clinical presentation the piece patients varies widely depending on the genotype and other potential disease modifying is.

Pieces. There are pieces zero is the most advanced form of the disease, but even in non pieces. There I'd be interested right patients. The phenotype is patients diaries for miles anemia sort of severe form with the disease, where patients are virtually no endogenous basically had been production.

Bettina M. Cockroft: The clinical presentation of these patients varies widely depending on their genotype and other potential disease modifiers. Beta-0, beta-0 is the most severe form of the disease, but even in non-beta-0, beta-0 patients, the phenotype of patients varies from mild anemia to a severe form of the disease where patients have virtually no endogenous beta-globin production and are clinically indistinguishable from beta-0, beta-0. As a reminder, our study enrollment criteria allows beta-thalassemia patients of any genotype, provided they're transfusion-dependent, with disease that is severe enough to have required at least eight packed red blood cell transfusions for each of the two prior years. It's notable that a competitor study using CRISPR-Cas9 editing technology allows enrollment of significantly less severe patients with potentially as few as four transfusion events per year for a typical adult patient.

They are clinically indistinguishable from pieces there are pieces era.

As a reminder of study enrollment criteria allows piece Italia, Santa seeming to patients with any genesight provided their transfusion dependent with disease that is severe enough. So if required to at least eight packs red blood cell transfusions for each of the two prior yes.

It's notable that a competitive study using CRISPR casnine editing technology allows enrollments have significantly less severe patients with potentially she was four transfusion events per year for typical adult patients.

Yes abstract posted this morning shows at the first three patients enrolled a ride the pieces. There are pieces zero, we'll have a severe genotype.

Disease phenotype functioning equivalent to features there I'd be severe patients.

The first patient has a pizza zero Peter Zero gene are tight this patients demonstrated prompt Siemens few ethic reconstitution with increasing fetal hemoglobin.

Bettina M. Cockroft: The ASH abstract posted this morning shows that the first three patients enrolled are either beta 0, beta 0 or have a severe genotype with disease phenotypes functionally equivalent to beta 0, beta 0 patients. The first patient has a beta 0, beta 0 genotype. This patient demonstrated prompt hemophilic reconstitution with increasing fetal hemoglobin. After being free from packed red blood cell transfusions for six weeks, the patient has subsequently required intermittent transfusions. At the time of the last follow-up, on-target DNA indels at BCL11A were present in the peripheral blood mononuclear, and fetal hemoglobin levels remained elevated at six months post-infusion. Patient 2 is a non-beta-0, beta-0 patient, but he has a severe genotype, where there's a near-complete absence of endogenous hemoglobin production. This patient experienced prompt haemopoietic reconstitution following infusion with on-target indels detected in circulating white blood cells, at the time of the last follow-up, and rising fetal hemoglobin levels observed through to 90 days post infusion.

After being free from pack read books, so transfusions for six weeks the patient has subsequently required intermittent transfusions.

Turning to last follow up on target DNA in goes at the seller. That's the main were present in peripheral blood mononuclear cells and fetal hemoglobin levels remained elevated at six months post infusion.

Patient too is a non pieces there I pieces here at patients, but has a severe genotype, where there's a near complete absence.

Infogenesis hemoglobin production.

This patients experience, prompting the classic reconstitution pulling infusion with on target in dose detected in circulating white blood cells at the time is a loss follow up and rising fetal hemoglobin levels.

Through to 90 days post infusion.

Patient three who is a non because there are pieces or a patient but has the severe genotype where there is need compete absence of intelligence hemoglobin production is the most recent been treated patients and received the S. T 400 infusion in August .

Besides the previously reported I see for patient, one which was an allergic reaction to the Tms cried protection in the product that is resolved by the end of the infusion.

No other resi east related to S. T 415 reported no. Other reports a days have been consistent with those expected floating manipulation.

Bettina M. Cockroft: Patient 3, who is a non-beta 0 beta 0 patient but has a severe genotype where there is a near complete absence of endogenous hemoglobin production, is the most recently treated patient and received the ST400 infusion in August. Besides, a previously reported SAE for patient one, which was an allergic reaction to the DMSO cryoprotectant in the product that was resolved by the end of the infusion. No other SAEs related to SG400 have been reported, and all other reported AEs have been consistent with those expected following mild ablation. Furthermore, no clonal hematopoiesis has been observed to date. As a reminder, our study is still very much in its early stages. Myeloablative conditioning, such as that used in this study, is a reboot of the haemopoietic system, and there are other myeloablative conditioning studies in this patient population have shown.

No clone organ, Massachusetts has been observed to date.

As a reminder of study is still very much in its early stages, my new ablative conditioning, such as that use in this study is a rebates as the hemolytic system and this all the mine to ablative conditioning studies in this patient population, who show him sufficient time is required for this.

Im cells to fully repopulate, the mirror and to try to massive police this.

This may take up to 12 months or even potentially longer.

Accordingly, the data that will show next month at Ash will be very preliminary reflecting and limited follow up from the first three patients dosed in the study.

We look forward to more mature results towards the end of 2020 once all of the patients have been ties and sufficient time has passed to allow for the full potential effects. The best T 400 to manifest and to understand how it impacts transfusion burden.

I'll now turn the call over 20, new CMO Bettina Coke Croft for clinical development and operations update.

Thank you atria and good afternoon.

I'm very pleased to have joined Sangamo as Chief Medical Officer, and I've spent the past few weeks meeting the various project team, bringing myself up to speed with the pipeline clinical development program.

Bettina M. Cockroft: Sufficient time is required for the stem cells to fully repopulate the marrow and to dry out from atopoiesis. This may take up to 12 months or even potentially longer. Accordingly, the data that we'll show next month at ASH will be very preliminary, reflecting only limited follow-up from the first three patients dosed in the study. We look forward to more mature results towards the end of 2020, once all of the patients have been dosed and sufficient time has passed to allow for the full potential effect of ST400 to manifest and to understand how it impacts transfusion burden. I'll now turn the call over to our new CMO, Virginia Cockroft, for a clinical development and operations update.

I was attracted to sangamo by Sandy genomic medicine vision, but also by upcoming flow it read out from the ongoing clinical trials and the second wave of promising pipeline candidates that will enter the clinic over the next few years.

Today I'm going to discuss the progress that we've made in several of our clinical program.

First I'll discuss our hemophilia 18 therapy candidate, which is partnered with tighter.

Activities the transitioning the I indeed to fight that are underway and progressing well.

We expect to complete the transition in the first quarter of 2020 .

The manufacturing technology transfer to Pfizer has been completed on the phase three drug supply is anticipated to be ready by the time fight that begins its phase three registrational study.

Pfizer announced it has enrolled at first patient in the six month phase three lead in study for Hemophilia gene therapy.

The data from this study are expected to provide baseline information to patients with subsequently enrolled into the Registrational phase three study, which is anticipated to be initiated in 2020 .

Bettina M. Cockroft: Thank you, Adrian, and good afternoon. I'm very pleased to have joined Sangamo as Chief Medical Officer, and I've spent the past few weeks meeting the various project teams and bringing myself up to speed with the Pipeline's clinical development program. I was attracted to Sangamo by Sandy's genomic medicine vision, but also by the upcoming flow of readouts from the ongoing clinical trials and the second wave of promising pipeline candidates that will enter the clinic over the next few years. Today, I'm going to discuss the progress that we've made in several of our clinical programs. First, I'll discuss our Haemophilia A gene therapy candidate, which is partnered with Pfizer. Activities for transitioning the IND to Pfizer are underway and progressing well. We expect to complete the transition in the first quarter of 2020.

Pfizer has been an excellent development partners throughout the process and we're excited to have them take this product fluid into late stage development.

It is our hope that positive results from this program will deliver on foot license product.

Turning now to our other gene therapy program as T. Ninetwenty Fabry disease.

I see Nytwenty was recently granted orphan drug designation by the FDA and received approval of the clinical trial authorization application, allowing expansion of the study into the UK.

A phase one two study now has four sites opened with to actively recruiting and we're on track to enrolled patients by the end of again.

We will explore three different dose cohorts and will present results. When we have a full set of data.

In addition to safety and Tolerability, which at the primary endpoint, we will be looking at plasma also go a activity.

Gbpthree substrate levels in plasma Leisel gbpthree in plasma and ultimately successful E. R. T withdrawal, which is the goal.

We believe that our extensive know how in a these six cassette engineering a the delivery on gene therapy dozing obtained from the ongoing hemophilia eight clinical trial has enabled us to design a fabry disease gene therapy that has the potential to deliver meaningful clinical impact to patient.

Bettina M. Cockroft: The manufacturing technology transfer to Pfizer has been completed, and the Phase 3 drug supply is anticipated to be ready by the time Pfizer begins its Phase 3 registrational study. Pfizer announced that it has enrolled its first patient in the six-month Phase 3 lead-in study for hemophilia gene therapy. The data from the study are expected to provide baseline information for patients who are subsequently enrolled into the Registrational Phase 3 study, which is anticipated to be initiated in 2020. Pfizer has been an excellent development partner throughout the process, and we're excited to have them take this product forward into late-stage development. It is our hope that positive results from this program will deliver our first licensed product.

We're encouraged by the draft FDA guidance on Fabry, which we believe will continue we shorten the time to approval and allow us to be among the first gene therapy treatment on the market.

Turning now to be decide to see me, which has partnered with Sanofi.

Following the started patient dosing, we have and $6 million milestone from Sanofi and $2 million from the California Institute for regenerative medicine.

As of today, we have enrolled five of the six patients that we expect in the study.

As Adrian mentioned, we will have preliminary data from this program next month at Ash with more complete and mature results expected in late 2020 . After enrollment is complete and went all six subjects have had sufficient follow up to evaluate the effects of treatment with SP 400.

Our other clinical trials and trial parted with Sanofi and Hemoglobinopathies, it's a sickle cell disease.

Bettina M. Cockroft: Turning now to our other gene therapy program, ST920, for Fabry disease. ST920 was recently granted U.S. orphan drug designation by the FDA and received approval of the clinical trial authorization application, allowing expansion of the study into the UK. Our Phase 1-2 study now has four sites open, with two actively recruiting, and we're on track to enroll the first patient by the end of the year. We will explore three different dose cohorts and will present results when we have a full set of data. In addition to safety and tolerability, which are the primary endpoints, we will be looking at plasma alpha-gal-A activity, GB3 substrate levels in plasma, lyso-GB3 in plasma, and ultimately, successful ERT withdrawal, which is the goal.

Takes a similar autologous cell therapy approach, we took out a senior.

Sanofi is currently recruiting patients in the phase one two open label precise in one trial.

Rating BBB double of three for a telogis hematopoietic stem cell transplantation in patients with severe sickle cell disease.

Turning to slide 34.

We have T X 200, our car T Reg program for a Chile to mismatched kidney transplant.

We're very excited about this first in human car T. Regs study and have recently submitted the SCPA.

And we expect to begin treating patients and 2020 .

As a reminder, about 20% of patients receiving kidney transplant haven't HL 82, mismatch with Donuts and this mismatches a coming cool transplant rejection in necessitates lifelong use of immunosuppressive drugs.

The hope is that the infusion with tier 200.

T Reg.

We'll suppress the immune response to the mismatched, Oregon.

This is an ideal size syndication for car T. Reg as these patients undergo regular kidney biopsies.

We will provide insight into a range of efficacy and safety measurement and will help demonstrate a mechanism of action of car T. Reg.

We very much look forward to presenting an in depth overview of our car T. Reg program and have good candidates T X 200.

I will now turn it over to the fun for the financial results in this important.

Thank you very good afternoon to home.

Has been my pleasure to serve US James ship over the last six months on be excited to welcome Saggy ASM CFO .

Bettina M. Cockroft: We believe that our extensive know-how in AAV6 cassette engineering, AAV delivery, and gene therapy dosing obtained from the ongoing Haemophilia A clinical trial has enabled us to design a Fabry disease gene therapy that has the potential to deliver meaningful clinical impact to patients. We're encouraged by the draft FDA guidance on Fabry, which we believe will considerably shorten the time to approval and allow us to be among the first gene therapy treatments on the market. Turning now to beta thalassemia, which is partnered with Sanofi. Following the third patient dosing, we have earned a $6 million milestone from Sanofi and $2 million from the California Institute for Regenerative Medicine. As of today, we have enrolled five of the six patients that we expect to enroll in the study.

So I guess formally to kind of of the whole on that we did he bought the financial section on future calls on before I discuss the financial update that we'd like him too. So if you will so.

Thank you Stefan and good afternoon, everyone. Its day five at Sangamo for me and I'm very excited about the opportunities that are ahead.

See tremendous potential into technology platform at Sangamo and the right talent to execute on the pipeline I'm pleased to join the leadership team and look forward to speaking with you in the future that's used upon.

Thank you. Thanks for the sub go out to has moved detailed financial statement included in the price could ease that we issued this afternoon.

Well I seem to Form 10-Q that Wi Fi Joe's before the school Accordingly, we only it has the highlights.

Bettina M. Cockroft: As Adrian mentioned, we will have preliminary data from this program next month at ASH, with more complete and mature results expected in late 2020 after enrollment is complete and when all six subjects have had sufficient follow-up to evaluate the effects of treatment with ST400. Our other clinical trial, a trial partnered with Sanofi and Hemoglobinopathies, is for sickle cell disease, which takes a similar autologous cell therapy approach as beta thalass Sanofi is currently recruiting patients in the Phase 1 to Open Label Precisin-1 trial, evaluating VIV-V003 for autologous hematopoietic stem cell transplantation in patients with severe sickle cell disease. Turning to slide 34, we have TX200, our CAR Treg program for HLA-A2 mismatched kidney transplants. We're very excited about this first in human CAR Treg study and have recently submitted the CTA, and we expect to begin treating patients in 2020.

Well the news for this quarter were 22 million compared to 20 323.6 million for the same day, adding 28.

The Dickies of 1.6 million was primarily driven by did decrease of 7 million in revenue related to the Pfizer effect a collaboration on 1.4 million already to way. It's usually when you have said by an increase of $6.5 billion annually to the Sanofi collaboration.

I don't Tc beta well getting expenses, including the sub Walter effecting the company's goals, including increased U.S. head count in support of the I can you couldn't bike ban on the clinical development program as well as manufacturing readiness activities.

Total operating expenses for this quarter were 51.2 million compared to 69.8 million for the send paying 2018.

And the expenses were 76.3 billion for the so called to Aplenty 19, compared to 28.8 median for the scintillating twin aging.

The increase is primarily due to increase your competition comes from headcount.

Bettina M. Cockroft: As a reminder, about 20% of patients receiving kidney transplants have an HLA-A2 mismatch with donors, and this mismatch is a common cause of transplant rejection and necessitates lifelong use of immunosuppressive drugs. The hope is that the infusion of TX200, the CAR-T reg, will suppress the immune response to the mismatched organ. This is an ideal first indication for a CAR-T reg as these patients undergo regular kidney biopsies, which will provide insights into a range of efficacy and safety measurements and will help demonstrate the mechanism of action of CAR-T regs. We very much look forward to presenting an in-depth overview of our CAR T-REx program and our first candidate, TX200, soon. I will now turn it over to Stefan for the financial results in this court.

Are you a facility expenses related to on you'll be has been facility on manufacturing expenses related to a teeny collection.

Gina expenses were 14.9 million in the quarter compared to 11 million for the same period in 2018.

The increase was primarily due to increased competition because you had come close on increased facility expenses.

Construction of our in House GMP, you need in Brisbane is proceeding on schedule on it we would do you expect to commence qualification closer do early next year.

I was at the end of September 2019, the company had cash cash equivalent on investment in the month of followed an 8.3 billion but off.

In line, we felt financial guidance, while 2019, we continue to project, Okay matching expenses endogenous two out on 10 to.

20 medium that off for the year.

We also expect that Joe on cash cash equivalent on investments should provide funds population foodie out of the 2020 what.

Stephane: Thank you, Bettina, and good afternoon to all. It has been my pleasure to serve as interim CFO over the last six months. I'm very excited to welcome Sang Lee as our new CFO. Sang has formally taken over the role and will report on the financial section on future calls. And before I discuss the financial update, I would like him to say a few words.

We know Tony back to Sunday felt closing remarks, thank you Stefan.

The primary focus a sizeable is the programs are currently in the clinic.

SP five to five in hemophilia B continues to generate promising data and he's been met with great interest from both the patient physician communities as well as from investors.

Sung Lee: Thank you, Stéphane, and good afternoon, everyone. It's day five at Sangamo for me, and I'm very excited about the opportunities that are ahead. I see tremendous potential in the technology platform at Sangamo and the right talent to execute on the pipeline. I'm pleased to join the leadership team and look forward to speaking with you in the future. Bye.

This is a really important moment for us as we transition SP five to five or lead us to Pfizer for late stage Registrational development.

It has also been instrumental in driving our future programs, most notably in Fabry disease, where we have a wholly own gene therapy candidate for which we expect to enroll their first patient this year.

Well gene therapy continues to be a near term value driver for sustainable.

We are the zinc finger company and we're also excited suppose the upcoming pipeline you choices you see offense NXP boot junior Twod cell therapy, and finally for in vivo genome editing and gene regulation using this year Pete transcription factors, which we still believe is the ultimate goal, but you know we've made some company.

Stephane: Thank you, Sang. For the third quarter results, detailed financial statements were included in the press release that we issued this afternoon, as well as in the Form 10-Q that we filed just before this. Accordingly, I will only address the I-line.

Stephane: Revenues for the third quarter were $22 million, compared to $23.6 million for the same period in 2018. The decrease of $1.6 million was primarily driven by a decrease of $7 million in revenue related to the Pfizer Factor VIII collaboration and $1.4 million related to YLP revenue, offset by an increase of $6.5 million in revenue related to the Sanofi collaboration. As anticipated, operating expenses increased in the third quarter, reflecting the company's growth, including increased U.S. headcount in support of the Preclinical Pipeline and the Clinical Development Program, as well as manufacturing readiness activities. Total operating expenses for the third quarter were $51.2 million, compared to $39.8 million for the same period in 2018. And the expenses were $36.3 million for the third quarter of 2019 compared to $28.8 million for the same period in 2018.

We will define those on the future of clinical medicine.

Thank you for joining us on the co today.

Operator, please open the co two questions.

Ladies and gentlemen to asked a question you would need to press Star then one well your telephone.

To withdraw your question. Please press the pound key.

Again that start one to asked a question.

Please standby, while we compile the culinary roster.

Our first question comes from the line of Maury Raycroft with Jefferies. Your line is open.

Hi, everyone. Congrats on the progress and thanks for taking my questions and welcome to the new additions to that to the team.

First question is just on the three patients discussed in the SD 400 abstract just wondering if from the different per kick doses are related to that Gino type or is there. Another reason for the different doses and what will the third patients get.

Progress each quarter.

So we.

Good afternoon, Murray, So if I understand your question correctly, you're asking about leasing assa and sell sell number and <unk>.

Stephane: The increase is primarily due to increased or higher compensation costs from Hedcom Grove, higher facility expenses related to our new Brisbane facility, and higher manufacturing expenses related to our clinical facilities. GNA expenses were $14.9 million in the quarter, compared to $11 million for the same period in 2018. The increase was primarily due to increased composition costs due to headcount growth and increased facility expenses. Construction of our in-house GMP unit in Brisbane is proceeding on schedule, and we will still expect to commence the qualification procedure early next year. As at the end of September 2019, the company had cash and cash equivalents on investment in the amount of $408.3 million. In line with our financial guidance for 2019, we continue to project operating expenses in the region of $210 to $220 million for the year. We also expect that Current Cash, the cash equivalent on investment, should provide funds for operations through the end of the year 2020. I will now turn it back to Sandy for closing remarks.

On the index on the CF fuse.

Yeah.

Manufacturing process for each patient is a bespoke process and so what you do as you exit the sales. So you can recover from that patient which varies from patient to patient.

And then put back as many as you can and so the process itself will unfold with time and with learning them with experience rather than a being a dose response experiment us as in other gene therapies or or other gene editing projects.

Got it it makes sense so.

So you're going to use that number itself, we have available credit patient Ben.

That's correct.

Okay, and then for the first patient.

That was treated if you can talk more about why the patient started to be transfusions. After six weeks the rate of intermittent transfusions in any thoughts on whether this patient what SAP required requiring transfusions going forward.

So we're happy to that kind of pass that went over to atrium, yes, Thats fine. Thanks for the question, who we appreciate and you know just like just reiterate you know obviously we call on.

You say too much about the dates for itself because of the Ash Rush Limbaugh ago. I think you know the important points the you'll see from what we said today.

Alexander D. Macrae: Thank you, Stefan. The primary focus at Sangamo is the programs that are currently in the clinic. SB 525 and Haemophilia A continue to generate promising data and has been met with great interest from both the patient and physician communities, as well as from investigators. This is a really important moment for us as we transition SB 525, our lead asset, to Pfizer for late stage registrational development. It has also been instrumental in guiding our future programs, most notably in Fabry disease, where we have a wholly owned gene therapy candidate for which we expect to enroll our first patient this year. Gene therapy continues to be a near-term value driver for Sangamo. We are the Zincfinger company, and we're also excited about the upcoming pipeline that utilizes these ZFNs in ex vivo gene-edited cell therapy and finally for in vivo genome editing and gene regulation using the ZFP transcription factors, which we still believe is the ultimate goal of a genomic medicine company and which will define us and the future of clinical medicine. Thank you for joining us on the call today. Operator, please open the call to questions.

We've got evidence that weve seen successful editing with the same thing going into these days.

That's safe that we've caught on target in those in PCL 11, a in the Pbmcs, we've seen increasing hps and successful.

Im a plastic reconstitution. So what you know specifically address your question I think really as as we said on the coal I mean, it's really early days and.

I think we need to leave sufficient time for the states it to evolve.

If you look at the supplementary information in New England Jono paper.

Blew by published you'll see that it can take very variable amounts of time for the full effect to kick in so I think we just need to works. This.

Hey, truthful and it's a little bit early to make me defensive comments on that and we look forward to showing more data over the course so.

Lisa 2020, when we will have to promote six if the patients.

Operator: Ladies and gentlemen, to ask a question, you will need to press star then 1 on your telephone. To withdraw your question, please press the pound key.

Got it Okay, and then you may have mentioned as but for the Dms. So.

I'm just wondering if I if you watch that out for the second patient that was dose.

Operator: Again, it's star number one to ask the question. Please stand by while we compile the Q&A roster. Our first question comes from the line of Maurice Raycroft with Jeffreys. Your line is open.

And if thats the plan to watch that out going forward.

Not all in London.

Maurice Thomas Raycroft: Hi everyone, congrats on the progress and thanks for taking my questions and welcome to the new additions to the team. First question is just on the three patients discussed in the SD-400 abstract. Just wondering if the different per-kig doses are related to the genotype, or is there another reason for the different doses? And what will the third patient get? A Paparazzi Foreigner.

It's not as much as much of washing your toe to it was it's making sure the patients are protected and we give them.

Tylenol and on T. histamine no routinely.

And just patient had previous reactions to CMS, so in and pack sales.

Please in platelets, so we haven't seen its in any other patients.

Got it Okay, and then I'm just I guess one last question based on the baseline transfusion rate versus competitors you guys mentioned that CRISPR Casnine company. That's also in the space I'm. If you could just provide any perspective into how we should compare and contrast data and I'm wondering if our regulators weight.

Alexander D. Macrae: So good afternoon, Maurice. So if I understand your question correctly, you're asking about the dosing as in cell number, the indels, and the CFUs. For each patient, the manufacturing process for each patient is a bespoke process, and so what you do is you edit the cells that you can recover from that patient, which varies from patient to patient, and then put back as many as you can, and so the process itself will evolve with time and with learning and with experience, rather than it being a dose response experiment as in other gene therapies or other gene editing projects.

Data it differently based on the baseline transfusion right.

I think both companies are a very early stage and we only we only have a handful of patients who have six by the end just next year.

I don't know how far along their friends or CRISPR I think you do need to pay Greeks attention to the.

Alexander D. Macrae: Got it. That makes sense. So, basically, you're going to use the number of cells that you have available for the patient. That's correct. Okay, and then for the first patient that was treated, could you talk more about why the patient started to need transfusions after six weeks, the rate of intermittent transfusions, and any thoughts on whether this patient would stop requiring transfusions going forward?

Genotype and phenotype of patient so can be a great range in.

In transfusion requirements.

We have chosen patients who is really significant to seize.

The CRISPR patients are milder, but I think until there's a substantial body of evidence for both companies it would be.

Adrian: So we're happy to do that. Can I pass that one over to Adrian?

Premature to to compare and contrast.

Got it understood. Thanks for taking my questions.

Adrian: Yeah, thanks for the question. We appreciate it. And, you know, I'd just like to just reiterate, obviously, we can't say too much about the data itself because of the ash embargo. But I think, you know, the important points that you'll see from what we said today are that we've got evidence that we've seen successful editing with the zinc finger nucleases, and we've got on target indels in BCL11A in the PBMCs We've seen increasing HBF and successful haemopoietic reconstitution.

Okay. So pleasure.

Our next question comes from the line of Gena Wang with Barclays. Your line is open.

Thank you for taking my questions I also have a few questions regarding the beta thalassemia data.

So we do understand because you know because you're going to most of the patient population.

Just wondering.

See any significant reduction in you really need yourself.

HM can you to this yes again I think we have to be very careful about.

Adrian: To, you know, specifically address your question, I think, really, as we said on the call, it's really early days. And I think we need to leave sufficient time for this data to evolve. If you look at the supplementary information in the New England Journal paper that Bluebird published, you'll see that it can take very variable amounts of time for the full effect to kick in. So I think we just need to watch this data evolve, and it's a little bit early to make any definitive comments on that.

Mentioning any specific dates from the school because of the Aschenbach I see if you don't mind will defer that too to December but thank you for the question do you know we're trying to be very careful to follow the guidance Abash.

We will show as much data as we can in December yeah, what would I can say, though is you know we've seen very happy with the Democrats. It reconstitution, we've seen so far.

Adrian: And we look forward to showing more data over the course of later 2020, when we'll have data from all six of the patients.

Okay, and then I don't know if you can comment did you see comparable editing efficiency across three patients so far.

Adrian: And then, you may have mentioned this, but for the DMSO, I'm just wondering if you watched that out for the second patient that was dosed and if that's the plan to watch that out going forward.

We'll show you that will show you for ever we can in December at Ash.

Okay [laughter]. Another question regarding the February you can see.

So you're expecting will first patients by the end of this year.

Adrian: [inaudible]

Adrian: It's not as much a matter of washing it out; it's making sure the patients are protected, and we give them Tylenol and antihistamine now routinely, and this patient had previous reactions to DMSO in Pax cells and platelets, so we haven't seen it in any other patients.

Just wondering will the initial dose be putting the therapeutic window and what would be the timing for the data update.

Patina.

So we're expecting the first patient patina, we hope to enrolled the first patient this year.

Next we hope to enroll the pain patients that you currently screening patients.

The start of the studies underway I think that's all we can say at this stage, yeah, and and as always the first time you're going to.

Alexander D. Macrae: Got it, okay. And then just one last question based on the baseline transfusion rate versus competitors. You guys mentioned the CRISPR-Cas9 company that's also in the space. If you could just provide any perspective into how we should compare and contrast data. And I'm wondering if our regulators weigh the data differently based on the baseline transfusion rate.

Clinical trial, we hope to give as much benefit as possible to the patients until we see the results of clinical trial, we can tell.

Okay.

You know Pandora.

You probably saw Sgc T.J., so with the.

Good luck, who Oh Gee like knockout model and you saw that we achieved super therapeutic levels that.

Forgot I am I don't think we've announced the doses.

Alexander D. Macrae: I think both companies are at a very early stage, and we only have a handful of patients. We'll have six by the end of next year.

We plan to use so I I when disclose those on this call. We've just said low medium and high yeah.

Okay.

And the timing for data update is it fair to say like second half next year, we should start to anticipate some data coming.

Alexander D. Macrae: I don't know how far along our friends are at CRISPR. I think you do need to pay great attention to the genotype and phenotype of the patient, as there can be a great range in transfusion requirements. We have chosen patients with really significant disease. The CRISPR patients are milder. But I think until there's a substantial body of evidence for both companies, it would be premature to compare and contrast.

I think we guided to the latter part of 20 to 24, a bike chemical data.

We hope to trial run smoothly recruits quickly and this is an important so.

Event for signing them or should we look forward to talking put it into next year.

Okay, great. Thank you.

Thank you.

Our next question comes from the line of Whitney Jim with Guggenheim Securities. Your line is open.

Maurice Thomas Raycroft: Got it. Understandable. Thanks for taking my question. Always a pleasure.

Hi, guys. Thanks for taking my question and congrats song and count on your old.

Operator: It's a pleasure.

Huidong Wang: Our next question comes from Gina Wang with Barclays. Thank you for taking my questions. I also have a few questions regarding the beta thalassemia data. So we do understand beta 0, beta 0 is the most severe patient population. Just wondering, did you see any significant reduction in urethral lineage cells?

Just had another question on a beta thalassemia I know at the April at it.

Update you kind of commented around 30% fetal hemoglobin.

How are you thinking about the desired level you feel hemoglobin you want to see going forward and are there any leverage can pull too.

And trimming of new patients and increased.

So thank you. Thank you for your your question and also thank you for acknowledging our new stuff I'm really pleased with the quality of people that were not able to attract both with patina and with some.

Adrian: Adrian, can you take this?

Adrian: Yeah, again, I think we have to be very careful about mentioning any specific data on this call because of the ash embargo, so if you don't mind, we'll defer that to December, but thank you for the question.

On a screen the management team is now complete.

Huidong Wang: Gina, we're trying to be very careful to follow the guidance of ASH, and we will show as much data as we can in December.

The.

We're all very early stage of understanding of the effective editing PCR little if any.

Alexander D. Macrae: What I can say though is we've been very happy with the haemopoietic reconstitution that we've seen so far.

I think that data that will accumulate over the coming year to 18 months will be essential to educate tow soon with or on on the utility. If this is an approach.

Adrian: Okay, and then I don't know if you can comment, you know, did you see comparable editing efficiency across three patients so far?

Got it and.

Adrian: We'll show you that; we'll show you whatever we can in December at ASH.

Follow on the manufacturing transfer to Pfizer I understand it's complete is there anything you can say on potential changes that occurred during that process as it was being transferred.

Huidong Wang: Okay, another question regarding Febreeze disease. So you expect to enroll the first patient by the end of this year. Just wondering if the initial dose will be within the therapeutic window, and what will be the timing for the data update?

Yes.

So thank you for that question and I know this this is something that a number if you fast.

The our friends at Pfizer or are very.

Bettina M. Cockroft: Bettina?

Pleased with the transition the or.

Bettina M. Cockroft: Bettina? So we're expecting the first patient between; we hope to enroll the first patient this year.

These the want everyone to new that is all under control and there's nothing remarkable happening they are keeping close squared there how did their manufacturing it but I just want to reassure everyone. The transition is going smoothly and there's nothing remarkable happening.

Bettina M. Cockroft: That's correct. We hope to enroll the first patient this year. We're currently screening patients, so the start of the study is underway. I think that's all we can say at this stage.

Got it and one last question for me can you comment on whether any patients have been treated in sickle cell trial.

Alexander D. Macrae: Yeah, and as always, the first time you go into a clinical trial, you hope to give as much benefit as possible to the patient, and until we see the results of the clinical trial, we can't do anything. The Bulletproof Executive, 2013

Hey, it's mcdavid, so that's up to Santa feed to comment on we've just been able to say that their recruiting the study.

Got it thanks for taking my question.

Thank you.

Next question comes from the line up Debjit.

Alexander D. Macrae: You probably saw our ads.

Adrian: You probably saw our ASGCT data with the... GLACO GLA knockout model, and you saw that we achieved supertherapeutic levels of alpha Galay, and I don't think we've announced the doses that we plan to use, so I won't disclose those on this call.

Telpad Yang with H.C. Wainwright your line is open.

Hi, guys. Congrats on all the progress this is Eric on fared better.

And I just want to add.

At the few liver enzyme elevation said theme SP 525 key tell if there's been any correlation with factor eight activity and the intensity at the liver enzyme elevation.

Adrian: We've just said low, medium, and high.

Adrian: Yeah.

Huidong Wang: Okay, okay. And the timing for data updates, is it fair to say that in the second half next year we should start to anticipate some data coming?

So I can only talk about the data that we've seen so far where are the we've shared so far which have shortened the we haven't lost factory activity.

Alexander D. Macrae: I think we've guided to the latter part of 2020 for biochemical data. We hope the trial runs smoothly and recruits quickly, and this is an important event for Sangamo, so we look forward to talking about it at the end of next year.

I'm very pleased with my clinical team here at the to a great job of monitoring the patients closely and quickly treating with steroids and as the data. This publicly available we have not seen any loss of activity.

Okay, that's great.

Whitney Jim: Okay, great. Thank you. Thank you. Our next question comes from the line of Whitney Jim with Guggenheim Securities. Your line is open.

And then Oh quake so the.

The initial increasing hemoglobin that you saw from treatment as key 400, which seems to perhaps.

Whitney Jim: Hi guys, thanks for taking the question and congrats on your new roles. I just had another question on beta thalassemia. I know at the April update, you kind of commented around 30% fetal hemoglobin. How are you thinking about the desired level of fetal hemoglobin you want to see going forward, and are there any levers you can pull in the treatment of new patients to increase that?

Diminish somewhat do you think that could be explained by.

Transection have short term precursors, Texas quickly died off and then you really need to wait for longer term Knapp track stem cells to replace them.

Or or do you think it contained.

I I as I said to us.

Alexander D. Macrae: So thank you for your question and also thank you for acknowledging our new staff. I'm really pleased with the quality of people that we're now able to attract, both with Bettina and with Sung, and it's great that the management team is now complete. We're all at a very early stage of understanding the effect of editing BCL11A. I think the data that we'll accumulate over the coming year to 18 months will be essential to educate us on whether the utility of this approach is justified.

So thanks for the question.

I think we'll learning about what happens when you.

This.

Enhancer repress are complex I think we'll learning about what happens when you due to the transplantation of the sales back.

I think we're learning about the various population so short term and long term progenitor cells that will hopefully gradually populi this patients MRO and lead to long lasting cure or in a long lasting.

Alexander D. Macrae: Got it. And I have a follow-up on the manufacturing transfer to Pfizer. I understand it's complete. Is there anything you can say about potential changes that occurred during the process as it was being transferred?

Need not to have transfusions, but <unk>, but let's wait and see over the next 12 to 18 months with six patients and we will we will know so much more.

Okay looking forward to thank you.

Alexander D. Macrae: Our friends at Pfizer are very pleased with the transition. They want everyone to know that it's all under control and there's nothing remarkable happening. They are keeping close to where they are, and how they're manufacturing it. But I just want to reassure everyone that the transition has gone smoothly, and there's nothing remarkable happening.

Thank you next question comes from the line up with you a lot with Cowen Your line is open.

Good evening, everyone consider taking your question.

Hello to all the can you focused sangamo.

My first questions on the fabric each program Sandeep, you said it used to present.

Whitney Jim: Got it. And one last question for me.

McDavid Stilwell: Can you comment on whether any patients have been treated in the sickle cell trial? Hey, it's McDavid. So that's up to Sanofi to comment on. We've just been able to say that they're recruiting for the study.

Presented data when you had a full set of data and that you mentioned, a bunch of biomarkers plots and biomarkers.

Alphago Gbpthree license GBC.

Whitney Jim: Got it. Thanks for taking the question.

What kind of full set of data mean for you.

Whitney Jim: Thanks for taking the question.

Oh patient cohort is that comparing one does <unk> person snack.

Devjit Chaptopadhyay: Thank you. Our next question comes from the line of Devjit Chaptopadhyay with H.C. Wainwright. Your line is open.

And.

Alexander D. Macrae: Hi guys, congrats on all the progress. This is Aaron from DebJit, and I just wanted to ask... Of the few liver enzyme elevations that you've seen from SB 525, can you tell if there's been any correlation with factor VIII activity and the intensity of the liver enzyme elevation?

Are we going are you going to wait until you actually withdrawal before you slip.

Thank you for your question you newest very well.

We have.

I have missteps occasionally in the past by releasing data from quarter to Tony.

I would much prefer to show you the two range of a study.

Devjit Chaptopadhyay: So I can only talk about the data that we've shared so far, which shows that we haven't lost factor activity. I'm very pleased with my clinical team here. They do a great job of monitoring the patients closely and quickly treating them with steroids. And based on the data that's publicly available, we have not seen any loss of activity.

I mean I understand that are some long term measures to.

We'll be too late for for for sharing and so bill Tryon.

If you the data when the when all patients have been twos.

And we'll try and give you as much as possible, but we think we're of the opinion to.

Alexander D. Macrae: Okay, yeah, that's great. And then real quick, the initial increase in hemoglobin that you saw from treatment with ST-400, which seems to perhaps have... Diminished somewhat. Do you think that could be explained by... Transfection of short-term precursors that just quickly died off, and then you really need to wait for the longer-term hematopoietic stem cells to replace them, or do you think it's something else?

It's better for you than better for us in better for patients. If we give a more robust did complete picture.

Got it anyway is biased see it can be biopsy part of this critical.

We haven't commented on biopsy.

I think we both new if the F D.

The change in guidance, where they've said that biopsy me a low an earlier registration and we too are interested in the second we will worked with the clinical tooman or regulatory people to understand where we make biopsy Carter the study.

Alexander D. Macrae: As I said, so thanks for the question. I think we're all learning about what happens when you edit this enhancer-repressor complex. I think we're all learning about what happens when you transplant the cells back into the patient. And I think we're learning about the various populations of short-term and long-term progenitor cells that will hopefully gradually populate this patient's marrow and lead to a long-lasting cure or a long-lasting need not to have transfusions. But we will wait and see over the next 12 to 18 months with six patients, and we will know so much more.

Got it.

No I [laughter] [noise].

I also mentioned in your hemophilia a data.

You are seeing signal that.

Yeah.

Hi.

And he can.

Can you comment on long haul.

Yes embargo.

I'll I'll pass it to Adrian to see as carefully as possible.

Yeah, and just remember the principally addressing.

You know data from I.S.T.H., and a tiny little bit of extra data at the time Andy.

Devjit Chaptopadhyay: Okay, I'm looking forward to it. Thank you.

Yolanda Britue-Ballard: Thank you. Our next question comes from Yolanda Britue-Ballard with Cohen. Yolanda?

Obstruct release, but if you recall it was from the day trim Melbourne I think what we're seeing here is.

Yolanda Britue-Ballard: Good evening, everyone. Thanks for taking the question. And hello to all the new folk in Sangamo.

A therapy this well tolerated.

Which.

The highest dose, which we believe this thing has a therapeutic dose we see no bleeding events nextraq to usage.

Alexander D. Macrae: My first question is on the Fabry program. Sandy, you said that you would present the data when you had, quote, a full set of data. And then you mentioned a bunch of biomarkers, plasma biomarkers, alpha-gal, GB3, and glyco-GB3. What does a full set of data mean for you? Is it a full patient cohort? Is it comparing one dose cohort versus the next? And are you going to wait until ERT withdrawal before you present something?

At the date and the data we show.

Kirker, a degree of correction that puts the patients into into the normal range.

We get a couple live a transition and very benign.

Great one LT elevations, which are rapidly managed and which do not in any way impact the degree of Factorized expression.

Alexander D. Macrae: Thank you for your question. You know us very well.

We see a relatively low.

Yolanda Britue-Ballard: I have misstepped occasionally in the past by releasing data at a quarter of the time. I would much prefer to show you the full range of a study. I understand that there are some long-term measures that will be too late for sharing, and so we'll try and give you the data of when all patients have been dosed, and we'll try and give you as much of it as possible, but we think we're of the opinion that it's better for you than better for us and better for patients if we give a more rounded, complete picture.

It's a subject variability within the high dose cohorts remember also by the way we're using off the dose of vow rocks at 313 that says six issar team.

In the dates right I appreciate your since your ability.

You also staying very highly differentiated kinetics, we were getting up there into normal range within seven to 10 days for US is 20 days.

Alexander D. Macrae: Got it. And is kidney biopsy part of this protocol?

We file rocks. We showed you are clear threshold effect.

Alexander D. Macrae: We haven't commented on biopsy. I think we both know of the FDA change in guidance where they said that biopsy may allow an earlier registration, and we too are interested in that, and we will work with the clinical team and our regulatory people to understand where we make biopsy.

And to clear dose response.

And you also see if you recall so it was sustained activity in cohort three are up two year at that time, so for all of the above reasons.

Yolanda Britue-Ballard: got it and apologies for the

Yolanda Britue-Ballard: You also mentioned in your hemophilia A data that you are seeing signals that suggest that your treatment 525 is differentiated. Can you comment on that without upsetting the action barter?

<unk> I think we're still in the position, where we can confidently leaf that we have the potential to deliver it differentiates its hemophilia Ray gene therapy going forward. Thanks, So doing then.

Adrian: I'll pass it to Adrian to say it as carefully as possible.

We we just need to ask yield to be patient to see the data into this year and then to hold hands with those over the coming six months a city to Folson hopefully gives everyone confidence that the efficacy has remained in the sangamo products, which would be them. The biggest differentiating feature and it's also worth.

Adrian: Yeah, and just remember that I'm principally addressing data from ISTH and a tiny little bit of extra data at the time of the abstract release. But if you recall, from the data in Melbourne, I think what we're seeing here is a therapy that's well-tolerated, at the highest dose, which we believe is the therapeutic dose, we see no bleeding events, no factor usage, and the data we showed, to a degree of correction that puts the patients into the normal range. We get a couple of transient and very benign grade 1 ALT elevations which are rapidly managed and which do not in any way impact the degree of factor VIII expression. Hence, we see relatively low inter-subject variability within the high-dose cohorts.

Mentioning you know the older patients that you saw because I can you talk about there's obviously had significant.

Disease burden you know they were truly severe disease and I think that it's important to recall as well.

Can you do you think it's more important to be differentiated on safety or efficacy versus the primary product.

I think safety is the thing that is a synacor know every one must have it because it's the corn to the patients.

Alexander D. Macrae: Remember also, by the way, we're using half the dose of Valrox at 313 versus 6013. You know, in the data from ISTH, you were seeing durability. You're also seeing very highly differentiated kinetics. You know, we were getting up there into the normal range within seven to 10 days versus 20 days with Valrox. We showed you a clear threshold effect and ClearDoseResponse. And you also, if you recall, saw that there was sustained activity in Cohort 3 for up to a year at that time. So for all of the above reasons, you know, I think we're still in a position where we can confidently believe that we have the potential to deliver a differentiated hemophilia-arrayed gene therapy going forward.

I think see efficacy question that everyone is our skin in the old if you ask when when we meet with you is will persist patients who are looking for a medicines that lasts a sufficient length of time I think we're lucky that the so farm dimensions of open relatively safe for such a fundamental benefit to patients.

Both our product tenfold rocks has been remarkably safe and know what the patients are looking for is consistency of effect.

Yes, thanks for taking my questions.

Thank you as a reminder, ladies and gentlemen, if you like to ask the question you may do so by pressing Star then one.

Adrian: Thanks Adrienne, and we just need to ask you all to be patient to see the data at the end of this year and then to hold hands with us over the coming six months as the data evolves and hopefully gives everyone confidence that the efficacy has remained in the Sangamo products, which would be the biggest differentiating feature.

Our next question comes from the line of Eric Joseph J.P. Morgan Your line is old.

Hey, guys. Thanks for taking the questions.

I guess the follow up on that lost your last point Sandy with the important thing around persistency I'm curious to.

Yeah, I get your current view on sort of the the import of.

Duration that you're seeing with in 2013 dose.

Alexander D. Macrae: And it's also worth mentioning, you know, that all the patients that you saw, because I can only talk about those, obviously, had significant disease burdens, you know; they were truly severe diseases. And I think that that's important to recall as well.

How strong of a read through do you think that has to persistency at the higher 313 dose and also whether we would see an updated look on a factory persistency at that lower dose at ash.

Yolanda Britue-Ballard: Sandy, do you think it's more important to be differentiated on safety or efficacy versus the bimer in products?

And I've a follow up.

So it's encouraging that the 113 dose persists and we have seen no sign of its liking, which is excellent and we'll show you more data for its a cash that is currently embargoed.

Alexander D. Macrae: I think safety is the thing that is sine qua non. Everyone must have it because it's important to the patients. I think the efficacy question that everyone is asking and that all of you ask when we meet with you is, will it persist? Patients are looking for a medicine that lasts for a sufficient length of time. I think we're lucky that so far the medicines have all been relatively safe for such a fundamental benefit to patients. Both our product and Valrox have been remarkably safe, and now what patients are looking for is consistency of effect.

We do data we've got.

It's in the public because all that we can talk about an ash will give you. Some more months. So the 313 will be up to almost 11 months worth of data and the $1.13 will consist will be continue to show you that.

And the the question I've been asked by some people is it something about the more efficacious too is that is more.

Yolanda Britue-Ballard: Got it. Thanks for taking the questions. Thank you. As a reminder, ladies and gentlemen, if you would like to ask a question, you may do so by pressing star. Then, our next question comes from the line of Eric Joseph with J.P. Morgan. The line is open.

Taxing to deliver and so I think called the $1.13 is encouraging it really is to three either to induce the everyone wants to see and we look forward to showing you in next month.

Eric Joseph: Hey guys, thanks for taking the questions. I guess to follow up on that last point, Sandy, about the importance of being around persistency, I'm curious to hear your current view on sort of the import of the duration that you're seeing with the 1E13 dose. How strong of a read-through do you think that has to persistency at the higher 3D13 dose and also whether we would see an updated look on factor VIII persistency at that lower dose at ASH? And I have a follow-up.

Got it got it.

That's helpful. And then just on Fabry is.

Understanding your point around.

Conservatism around disclosing doses.

I guess, if there are there different safety considerations in the fabry population that your recruiting when it comes to.

Dose selection compared to he may, particularly around liver sensitivity I'm also curious to know whether your.

Alexander D. Macrae: So it's encouraging that the 1E13 dose persists and we have seen no sign of it flagging which is excellent and we'll show you more data for it at ASH that is currently embargoed. The data we've got that's in the public is all that we can talk about and at ASH we'll give you some more months so the 3E13 will be up to almost 11 months worth of data and the 1E13 will be continued out and we'll show you that and the question I've been asked by some people is if it's something about the more efficacious dose that is more taxing to the liver and so I think although the 1E13 is encouraging it really is the 3E13 dose that everyone wants to see and we look forward to showing you in next month.

Employing prophylactic steroid use.

It would.

Yeah, no, we're not really expecting the safety profile to be any different you know we're using the same have plateaued trophic a V six sector, which we believe played a key role in the in the success. So from SP five to five we're also.

Using a constructs which is near identical so we believe there will be read through passive safety.

And of efficacy.

And yes, we can we obviously you can't disclose the dose other than to reference the Gao Kao mouse states, which was.

Eric Joseph: Got it, got it. That's helpful.

Adrian: And then just on Fab Ray's... Understanding your point about disclosing doses, I guess, are there different safety considerations in the Fabry population that you're recruiting when it comes to dose selection compared to HME, particularly around liver sensitivity? I'm also curious to know whether you're employing prophylactic steroid use. Adrian?

Very compelling.

Sorry was the one that was one other thing you said.

So I think he also with us or do you feel like prophylactic, we already happen. We haven't comment we haven't commented on that yeah.

Got it got it and Eric.

Final question, if I could be that might.

Adrian: Yeah. No, we're not really expecting the safety profile to be any different. You know, we're using the same hepatotrophic AV6 vector which we believe played a key role in the success of SB525. We're also using a construct that is nearly identical. So we believe there will be read through both of safety and of efficacy, and yeah, we obviously can't disclose the dose other than to reference the GAL-KO mouse data, which was very compelling. I'm sorry, was the...

I guess, what how should we thinking about a clinically meaningful reduction in Portland, Gbpthree or life LIFO TV three as we.

I guess as that might informed.

Phase two dose selection.

Oh my goodness.

It's great to be thinking over the next phase of development the.

We will learn and watch what happens so I think we've all been interested in the pro bio data, where the they should some to some reduction in plasma levels and significant effects and the kidney, suggesting that we're all learning about the relationship between the pharmacokinetics and the tissue.

Eric Joseph: No, I think he asked you. Yes, sir.

Adrian: [inaudible]

Eric Joseph: Got it, got it. Yeah, final question, if I could, if you don't mind. I guess, what should we be thinking about a clinically meaningful reduction in plasma and GB3 or lyso-GB3 as we, I guess, as that might inform, you know, phase two dose selection.

Alexander D. Macrae: Oh, my goodness. It's great to be thinking about the next phase of development. We will learn and watch what happens. I think we've all been interested in the AbroBio data where they showed some reduction in plasma levels and significant effects in the kidney, suggesting that we're all learning about the relationship between the pharmacokinetics and the tissue effect of this. So we will show you the data as we go. And the most important thing is, can the patients come off of their ERT? And that really is the goal that we're all trying to aim for.

Effect of this so we will show you the data as we go the most important thing has come the patients come off of the or their ERP and not that really a signal that we're all trying to him for.

Got it thanks for taking the questions guys.

Thank you. Our next question comes from a line of Jim Birch enough well from Wells Fargo Securities.

Your line is open.

Hi, Thanks for taking the questions. This is the yen in for Jim.

Eric Joseph: Got it. Thanks for taking the question.

So first just wondering for the Pfizer phase three study.

Eric Joseph: Got it. Thanks for taking the time.

So we were it not to use a profit prophylactic steroids or have you commented on it.

Eric Joseph: Thank you. The next question comes from Alana.

Yanan Zhu: and Jim Birchinoff, Wells Fargo Security. Your line is open.

We haven't commented on Pfizer nobody will be responsible for talking about it. So we were very careful to respect their privilege.

Yanan Zhu: Hi, thanks for taking the questions. This is Yanan here in place of Jim.

Yanan Zhu: So first, just wondering, for the Pfizer phase 3 study, will it not use prophylactic steroids? Or have you commented on that?

Got it and then could you talk about the.

Alexander D. Macrae: We haven't commented, and Pfizer will now be responsible for talking about it, so we're very careful to respect their privilege.

Interest in for the enrollment.

Fabry study and particularly you can it can shed some light on relative preference for.

Yanan Zhu: Got it. And then, could you talk about the interest in the enrollment of the Fabry study and, particularly, if you can shed some light on relative preference for different gene therapy approaches, that would be helpful.

Different gene therapy approaches that would be helpful. Thank you.

Can you repeat the question to make sure. We are it's time to please yes, so the interest from physicians and patients and participating in the fabry.

Alexander D. Macrae: Can you repeat the question to make sure?

Yanan Zhu: Please.

Alexander D. Macrae: So there is an interest from physicians and patients in participating in the FABRI AAV gene therapy, especially with the context of other gene therapy approaches for FABRI, such as the lentiviral approach.

ABTS therapy.

As it is specialty for that with the context of other gene therapy approaches for fabry, such as Lentiviral approach.

Alexander D. Macrae: So, you would have to ask them. What I can say is that since our last set of clinical trials, we have had a new head of clinical operations, a remarkable woman, who has done a great job of setting the study up. And we have had a lot of interest from investigators who are all looking for something to bring to patients.

Thank you you would tap test them well I can see as we since our last set of clinical trials, we have a new head to clinical operations.

A remarkable women who is made a great job with setting the study up and we have had to lots of interest from investigators who are looking for something to bring to patients.

Yanan Zhu: Got it. And lastly, just on TX200, wondering if you plan to use lymphodepletion for that kidney transplant setting. And if so, what regimen? And also, for your future more broader development in autoimmune disease, how do you think of lymphodepletion in the setting of TRAG therapy? Thanks.

Got it.

And lastly, just on kicks 200 wondering if you plan to use lymphodepletion for that.

Any transplant setting.

And if so what regimen and also for broad for your future more broader divestment in auto immune disease. How do you think of Lymphodepletion in this with in this setting.

Brad therapy. Thanks.

Adrian: Adrian, do you have any thoughts on that?

It didn't you ever thought on that yeah, I think I think it honestly at this point I would.

Adrian: Yeah, I think honestly at this point, I would, I mean, it's a great question, but I would rather not disclose details of how we plan to, you know, as you know, it's suddenly becoming a very, very competitive area, and we've not disclosed any of those types of details. I think at this juncture, it would be prudent for us not to, if you don't mind. But, you know, obviously a very relevant question.

It's a great question, Paul I would rather not disclose details of how we plan to yeah actually you know, it's becoming suddenly it's very very competitive area. We've not disclosed something if those types of T cells and I think if at this juncture it would be prudent for us not not to do that mine.

You know, obviously, a very rather from question.

Yanan Zhu: Got it. Got it. Thank you. Thank you for taking all the questions. Our pleasure.

Got it got it. Thank you. Thank you for taking all the questions.

Our pleasure.

Alexander D. Macrae: Thank you. I'm not showing any further questions. I would now like to turn the call over to Sandy Macrae for closing remarks.

Thank you I'm not showing any further questions.

I'd now like to turn the call over to Sandy Mcrae for closing remarks.

Alexander D. Macrae: Thank you and thanks again to everyone for joining the call and for all your questions. We hope you'll join us for R&D Day next month on December 17th, and we look forward to keeping you updated on future developments. Have a good day.

Thank you and thanks again, everyone for joining the Coke and for all your questions. We hope you'll join US for the R&D day next month in December 17th and we look forward to keeping you updated and future developments.

Good day.

Operator: Ladies and gentlemen, that concludes today's conference. Thank you for participating. You may now disconnect. Everyone have a wonderful day.

Ladies and gentlemen that concludes today's conference. Thank you for participating you may now disconnect everyone have a wonderful day.

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