Q2 2019 Earnings Call

Operator: BF-WATCH TV 2021

Operator: Ladies and gentlemen, thank you for your patience and for standing by. Your conference call will begin momentarily. Again, ladies and gentlemen, thank you for your patience and for standing by.

Ladies and gentlemen, thank you for your patience and for standby Your conference call will begin momentarily again, ladies and gentlemen, Thank you for your patience and for standing by your conference call will begin momentarily.

Operator: BF-WATCH TV 2021 BF-WATCH TV 2021

Operator: Good afternoon, and welcome to the Sangamo Therapeutics teleconference to discuss second quarter 2019 financial results. The call is being recorded. I will now pass over to the coordinator of the event, McDavid Stilwell, Vice President of Corporate Communications and Investor Relations. The floor is yours.

McDavid Stilwell: Hello, and thank you for joining us. As we begin, I'd like to point out that we have posted our updated corporate presentation on the Sangamo website, and we'll be referencing several of these 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 this 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 product, and the potential for its product candidates to provide clinical benefit to patients.

The call is being recorded.

I'll pass over to the coordinator via that David Stilwell, Vice President of corporate Communications and Investor Relations.

Floor is yours.

Thank you for joining us.

We began.

Now that we have adjusted our updated corporate presentation to the SEC website.

We'll be referencing several of these slides today.

The slide presentation may be found on our website.

Think about dot com.

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

McDavid Stilwell: Sangamo's Development and Manufacturing Plan and Sangamo's expectations regarding its financial performance. However, 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. These forward-looking statements are not guarantees of future performance and are subject to certain risks, 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 foregoing 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 on the call this afternoon are several members of the Sangamo Senior Management Team, including Sandy Macrae, Chief Executive Officer, Adrienne Wilson, Head of Research and Development, Gary Loeb, General Counsel, and Ed Rebar, Chief Technology Officer. And again, as a reminder, during the call, we will refer to several slides in our corporate presentation. And those slides are to be found on the events and presentations page of the investors and media section of the

I'd also like to remind everyone that the projections and forward looking statements that we will discuss during this conference call.

Or 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 sacrifice genomic medicine platform products.

The potential for satcom product candidates to provide clinical benefit to patients.

Second as development and manufacturing plans.

And second most expectations regarding its financial performance.

Actual results may differ substantially from what we discuss today.

No one should assume at a later date our comments from today are still valid.

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

Specifically, 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 need and undertakes no duty to update such information, except as required under applicable law.

With me this afternoon on the call are several members of the second most senior management team, including Sandy Macrae Chief Executive Officer.

Adrian Watson head of research and development.

Alexander D. Macrae: Now I'd like to turn the call over to Sandy. Thank you, McDavid.

Gary No General counsel.

And that rebar Chief Technology Officer.

Alexander D. Macrae: Thank you, guys.

Alexander D. Macrae: and Good afternoon to everyone on the call. Thank you all 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, xBeef, or gene-edited cell therapy, in Z-Board Genome Editing and Gene Regulation. We are accelerating near-term opportunities with gene therapies because gene therapy is practical now and has defined regulatory pathways and well-documented manufacturing processes, and because it can provide immense value to patients. It also leverages our extensive experience in transgene and cassette engineering. We continue to advance ex vivo gene edited cell therapy because we've shown that we can do it well with our foundational HIV cell editing studies. It has a relatively straightforward application that builds on the science of our core CFM platform technology.

And again as a reminder, during the call we will refer to several slides in our corporate presentation.

And then finally to be found on the events and presentations page of the investors and media section of the site.

Now I'd like to turn the call over to Sandy document, David and good afternoon, everyone on the call.

Thank you all for joining us.

That cycle, 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 dissolve the underlying genetic causes of disease, using whatever technology space suits its different that treatment.

Including gene therapy.

X before gene editing cell therapy.

In seafood genome editing.

Gene regulation.

We are accelerating near term opportunities the gene therapies, because gene therapy is track Tonight.

And has defined regulatory pathways and well documented manufacturing processes.

Because it can provide immense value to patients.

He also leverage his extensive experience and transgene 'cause site engineering.

We continue to advance ex vivo gene edited so because we've shown that we can do well with our foundational HIV self testing studies as a relatively straightforward application that builds on the science of course, yes, I'm platform technology.

Alexander D. Macrae: And because it's an emerging approach with a defined regulatory pathway and significant therapeutic potential, which is understood by both the medical and the patient community. Finally, we're building momentum toward in vivo genome editing and gene regulation, as we believe that they are the therapeutic approaches that will define the future and transform the practice of clinical medicine. We're continuously learning from our experience and improving our technology and believe that we will solve the technical challenges associated with efficient delivery that are likely to be necessary to achieve successful in vivo editing. Given the tremendous diversity and optionality inherent to our platform, we are sometimes asked how to prioritize our education.

Cost is an emerging approach the defined regulatory path, we have significant therapeutic potential which is understood by both the magical and the patient communities.

Finally, we're building momentum towards in people genome editing and gene regulation as we believe that they aren't the therapeutic approaches to point in the future and transform the practice of clinical medicine.

We are continuously learning from our experience and improving our technology and believe that we will solve the technical challenges associated with delivery.

Are likely to be necessary to achieve successful in people entity.

Given the tremendous diversity and optionality inherent to our platform, we're sometimes asked how to prioritize our indications.

Alexander D. Macrae: The answer is that we select potential indications that satisfy four key criteria. Firstly, they address a significant unmet medical need. Second, that the underlying biology is well understood, and third, that our suite of genomic medicine technologies have the potential to efficiently address the relevant underlying molecular abnormalities. And finally, that there is sufficient potential commercial value. In the context of these core criteria that inform and define our strategy, I would also like to discuss our portfolio of priorities.

The answer is that we select potential indications and successfully for key criteria.

Personally at the address a significant unmet medical need.

Second.

Underlying biology is well understood.

All right, that's our suite of genomic medicine technologies have the potential to.

I shall be addressed the relevant underlying molecular abnormalities. Unfortunately, there is suspicion potential commercial value.

In the context of these core cartoon form to fight our strategy.

I'd also like just comes from.

Pull apart.

Alexander D. Macrae: Portfolio Prioritization Within the Context of the Three-Principle Developmental Ways at Sangamo, week one of our New York time opportunity, includes programs that are in the clinic or close to entering the clinic and have the potential to deliver approved products within the next few years. These include the Haemophilia A and Fabry Disease Gene Therapy Program, which are ex-human gene editing programs in beta thalassemia and sickle cell disease And our cellular therapies include our CD19 CAR-T, our TX200 CAR-T reg for HLA-A2 mismatch in renal transplant patients, and our in vivo genome editing program.

Portfolio prioritization within the context of the steep principal development two waves and site.

We won on or near term opportunities includes pro crops are in the clinic or close to entering the clinic.

I have the potential to live.

Within the next few years.

These include the hemophilia, a and part B disease gene therapy programs.

Our ex vivo gene editing programs would be $10 see man sickle cell disease, and our cellular therapies include our Cdnineteen car T.

T X 200 car T Reg for each lead to mismatch.

On spot patients.

In people genome editing.

The experience gained to need clinical applications for various technologies and an understanding delivery in engineering.

Alexander D. Macrae: The experience gained in the clinical applications of our various technologies and in understanding delivery and engineering both informs our prioritization and enables us to build the path forward for strong next wave of clinical candidates. Weave 2 or mid-term opportunities are programs that we expect to progress into clinical trials within the coming years. These include follow-on gene therapy products for rare diseases, currently reg programs for autoimmune and inflammatory diseases under CMS. These programs incorporate improvements to our platform technologies that build upon many of the lessons learned from our earlier clinical studies. Wave 3, or our Long-Term Opportunities, will include projects that will utilize new technologies currently under development.

Most importantly, our current position enables us to build the path forward our strong next week clinical candidates.

We have to or mid term opportunities are programs that we expect to progressing to the clinic within the coming years.

These include follow on gene therapy products, a rare disease.

Come to break programs for altering in summit two diseases.

I don't see it as possible.

These programs and copy improvements to our platform technologies to build upon many of the lessons learned from our clinical studies.

We are.

On our long term opportunities.

Quick projects that will utilize new technology is currently under development cycle.

Alexander D. Macrae: We expect these to help define the long-term future of our company and to redefine the field of genomic medicine. These would include extensions to our core gene editing and genome targeting capabilities, including novel strategies for integrating and editing genes, as well as an expanded set of options for efficient and precise in-person delivery. As a fully integrated clinical stage company, it's clearly important to prioritise wave one, the near-term value drivers, as these promise to bring medicines to patients in need the soonest. This strategy enables us to realize the near-term value of our portfolio while at the same time building a sustainable long-term pipeline.

We expect these to help define the long term future of our company and to redefine the future generally meds.

These would include extensions to our core gene editing and genome targeting capabilities, including multiple subsidies for integrating that into genes as well as an expanded set of options for efficient and precise people right.

As a fully integrated clinical stage company is clearly important to Prioritise. We've won the near term value drivers as these promise to bring medicines to patients in need soonest.

The strategy isn't it was supposed to be like near term problems or older.

But at the same time building a sustainable long term like fun.

This quarter's accomplishments illustrate how do we continue to make progress across a few weeks and sanguine tepid season has progressed as being formed by lessons from our experiences and then you an emergency medicine.

Alexander D. Macrae: This quarter's accomplishments illustrate how we continue to make progress across the three ways of Sango activities and how this progress has been formed by lessons learned from our experiences in the new and emerging field that you know we've encountered. By way of example, last month at the Congress of the International Society of Thrombosis and Haemostasis, or ISTH, in Melbourne, Australia, we presented updated Phase 1-2 results for FB525, our investigational haemophilia gene therapy candidate in partnership with Pfizer. We are pleased that the data continues to look promising and may represent a well-tolerated, predictable, and reliable product candidate. In the SB525 program, we observed significant increases in efficacy above a defined vector dose threshold as the dose was increased from 1E13, where factor VIII production was measurable but low, to 3E13 VG per kg, where factor VIII activity rises well into the normal range.

By way of example last month, the Congress of the International Society on thrombosis, and haemostasis or I guess to use in Melbourne, Australia.

We presented updated phase one two results for SP, five to five or investigational hemophilia gene therapy candidate partnered with Pfizer.

We were pleased that the team continues to look promising and represent a well tolerated predictable and reliable product comes with it.

[noise] NSP fight to fight program, we observed significant increases in efficacy up a defined term post threshold. So to US was increased from 2013 were factory production was measurable but move to eat 13 Vg per kg, we're factory activity prices well into the normal range.

Alexander D. Macrae: This taught us a lot about AAV6 transduction behavior and the efficiency of AAV6 transduction in humans. These learnings are likely to be helpful for our in vivo genome editing studies where we use the identical AAV6 vector as our delivery vehicle. We're using this information to help improve delivery in our in vivo genome editing clinical trials by increasing transduction efficiency and, thereby, editing efficiency. And I've asked Adrian to speak more about the SB525 results and how these insights are helping us to make improvements in our in vivo genome editing platform later this year. In addition to the compelling clinical data that we're obtaining, we've recently published two manuscripts in the high-impact journals Nature Medicine and Nature Biotechnology, which describe novel and powerful approaches for engineering zinc finger transcription factors for ambulo-specific depression, as well as how zinc finger nucleases can be engineered to enhance their genome-wide editing specificity in a way that substantially extends their therapeutic utility.

This taught us a lot to the 86 construction behavior.

Mission CTP six construction in humans.

These learnings are likely to be helpful partner in vivo genome interesting studies, where we use the identical 86 sector as our delivery vehicle.

We are using this information to help improve delivery center in people you know matching clinical trials by increasing transduction efficiency, thereby the editing efficiency and I ask Adrian to speak more about that.

SP five to fight results and had these insights are helping us to make improvements in our in vivo genome editing platform, we thrown in the year.

In addition to the compelling clinical data that we are teaming with recently published two manuscripts in high impact Journal nuclear medicine, and B to buy technology, which is quite hopeful and powerful approaches for engineering zinc finger transcription factors for a few specific depression.

Israel is hosting finger nucleases can be engineered to enhance their genome editing specificity and it's been a substantially extends the therapeutic utility.

Alexander D. Macrae: These publications illustrate how our commitment to innovative science enables new therapeutic opportunities, and I've asked Ed Rieber to describe these two papers in more detail later in the call. Before I turn the call over to the leadership team, I'd like to introduce our newest member, Gary Loeb, who has recently joined Sangamo as EVP and General Counsel. Gary will lead all of our legal affairs and has over 20 years of experience in biotechnology and pharmaceutical law, compliance, intellectual property, and litigation. We are truly delighted to have him on board; I look forward to working together with him as we continue to grow as a clinical stage development company and enter into commercialization. I'll now turn the call over to Adrian Wilson, who will provide more detail on our clinical updates. Adrian

These publications illustrate our commitment to innovative science any post new therapeutic opportunities and if instead report to describe these two papers more detail the DRONCO.

Before I turn the call the parts and leadership team I'd like to introduce our newest member Gary Lu who has recently joined saying as SVP and General counsel.

Gary will lead all of our legal affairs, and just over 20 years of experience and biotechnology and pharmaceutical compliance intellectual property litigation.

We're trying to like to touch on board I look forward to working together and as we continue to grow as a clinical stage development and it turns the commercialization phase.

I'll now turn the conference in Boston will provide more detail on our clinical updates.

Thank you Sandy and thanks to everybody on the call for joining us today.

Adrienne Wilson: Thank you Sandy and thanks to everybody on the call for joining us today. I'd like to start by elaborating on the SB55 haemophilia rate gene therapy results we recently presented at ISTH. And that was a meeting that I was fortunate enough to attend. While I was in Melbourne, Australia, I was really struck by the powerful excitement in the room about the potential of gene therapy and by the way in which it provides such an enormous improvement over the standard of care for haemophilia A patients, and especially by the intensity of the medical community's interest in our clinical data. And it's really remarkable to see how gene therapy, even at these early stages, has already transformed patients' lives, and this makes us all the more motivated to work with Pfizer to get a product into the market as swiftly as possible.

I want to start by elaborating on the SP five to five hemophilia raging sorry, if you recall, we recently presented at last year and that was a meeting I was fortunate enough to attack.

A woman Melbourne, Australia, I was really struck by the public cytokines in the row crop protection of gene therapy.

No way in which we provide such an enormous improvement over the standard of care.

Okay, Messineo ray patients and especially by the intensity so medical community's interest.

Okay.

That's really remarkable to see how gene therapy.

He does he stages has already transformed patients' lives.

Thank you saw us move more motivated to what Pfizer, It's got a product into the market was swiftly as possible.

Adrienne Wilson: And the ultrastudy data presented at ISPH by our PI, Barbara Conkle, details the results of 10 patients treated across four different ascending dose cohorts. These were 9E11, two patients treated, 2E12, two patients treated, 1E13, two patients treated, and 3E13, four patients treated. SB 55 was generally well tolerated, and unlike other studies, patients on the after study were not treated with prophylactic steroids. A single treatment-related serious adverse event was reported, but this patient experienced hypotension and fever six hours after completing the sp525 infusion. It was fully resolved with treatment, and the patient was discharged as planned within 24 hours of the onset of the event, and we haven't seen any similar grade 3 hypertension events subsequently.

He also study data presented last year its final appeal I offer comical.

Picked up the results of 10 patients treated across four different spending levels. These for 911.

C patients treated to Charles two patients treated when he started saying to patients treated three school, so asking for pensions tranches.

Espeed spicy fyfe was generally well tolerated and unlike other studies patients on me up the study were not treated with prophylactic steroids.

I think some treatment related serious adverse events reported.

I mean, this patient's experience hypertension or FIFA six hours after completing the SP five to five.

Sure.

Putting this all three treatments patients discharged pardon.

24 hours on the onsite will be events.

And we don't see very similar grade three hypertension or events subsequent.

Adrienne Wilson: Treatment-related adverse events in this study are detailed on slide 14. No patients treated with SP55 had a loss of factor VIII expression associated with an alanine aminotransferase elevation. However, in the 313 cohort, two subjects experienced a transient grade 1 ALT elevation, which was around greater than 1.5 times the baseline.

[noise] treatment related adverse events spotty here at Ti talent on slide 14.

That patients treated we've asked the parties five cover losses to raise expression associated with me I mean, I mean, I mean, our troms phrase that innovation.

313 cohort two subjects is experiencing strong see a great one.

She has a nation which was around.

Great.

<unk> five times the baseline.

Adrienne Wilson: But both of these patients were successfully managed with a tapering course of oral steroids. Slides 15 to 16 in our presentation show factor VIII activity across the different dose cohorts as measured by both the one stage assay and the chromogenic assay. And as you can see, patients demonstrated a dose-dependent increase in factor VIII activity with a pronounced increase in factor VIII activity as the dose was increased from the 1-13 dose to 3-13. And we believe that this provides evidence of a threshold effect in AV6 transduction and that this may be relevant to our understanding of clinical programs that use the same AV6 factor. And it's worth also noting that in the two patients treated at the 1-E13 dose, factor VIII activity levels have been durable through to the time of the data cutoff, which is respectively 52 and 32 weeks.

But most of these patients were successfully package.

Print Colestipol steroids.

Slide 15 to 16 year old presentation true traits activity across the different parts towables as measured by gross.

The one stage Android chrome and trying to test things that you can see patients demonstrated a times it depends in increase in fact strikes activity with the pronounced increase in stock trades activity. That's it dose was increased from the 113.

It's a three star team.

We believe this provides evidence of a threshold effects, an 86 Trump assumption.

This may be irrelevant swap is thinking about clinical programs the same decent specs out.

That's wonderful I think I think that in the two patients treated the warranties 13 times.

Trace activity levels have been terrible threats and it's hard to say to Kosovo, respectively, 50 to 52 weeks.

Adrienne Wilson: I'm turning now to slide 17, which focuses on the factor VIII activity levels of the four patients treated in the high-dose 313 cohort that were measured using the chromogenic assay. For these patients, factor VIII activity data were available through to 24, 19, 6, and 4 weeks of follow-up, respectively. The first two patients treated in the 313-dose cohort, patients 7 and 8, remained within their factor VIII activity normal range, as measured using the chromogenic assay, through weeks 24 and 19, respectively. The next two patients in the 3-13 cohort, patients 9 and 10, with 6 and 4 weeks of follow-up, respectively, demonstrated rapid factor VIII activity kinetics that generally appeared consistent with those of patients 7 and 8, which were measured at similarly early time points. As shown in slides 18 and 19, no patient treated at the 313-dose cohort had any documented bleeding events at all at the time of the data cut-off, and neither have patients in this dose cohort required factor VIII replacement following the initial use of prophylactic factor.

Turning now to slide 17, which focuses on the stock trades activity levels of the four patients treated in the high Thirtys Threes 13 cohort. This message using the crime is trying to say.

For these patients spot trace activity takes who were favorable three to 20 419 six.

A follow up respectively.

Two patients treated ministries heart teams I've traveled bits of patient center names.

Remains within the factory activity normal range, that's Mexicans using the perimeter and the cafe through week 24, and 19, respectively.

The next two patients in this respect team terrible actions by that time.

Thanks for the follow up prospectively demonstrates its rapid tax rate activity kinetics.

Which are pretty appears consistent with those of patient segment names, which we measure it separately Ivy talking points.

As shown in slide 18, or 1990 patient treated three sites. He says no then documented.

The tool.

Time is it takes a cut off.

Patients in this.

I was kind of what the court spots ranked replacement following the initial use of personalized.

Adrienne Wilson: Now, it will clearly be important to continue to follow these patients in order to determine the long-term durability of the response to 525 and to determine whether these results are recapitulated in subsequent patients. Persistence to factor VIII activity is important, and the data will need to mature for a longer duration to determine the durability of the response, and we plan to present longer-term follow-up data from these patients later in the year. But I'm happy to say that based on these data, the program was recently granted Regenerative Medicine Pharmacotherapy, or RMAP, status by the FDA. This designation allows the FDA to be more responsive to our requests for meetings and has the potential to expedite the regulatory process in the context of the planned Phase 3 registration or study.

We will continue to be important to continue to follow these insurance you know whats it to Tom long. Some jure affinity is in response to five to five.

Determine whether these results recapitulated in subsequent patients.

With the stock trading activity is important.

So we need to mature for a longer duration to determine the true.

Arms, and we talked about that longer term follow up data from these patients they true yes.

Based on these data program was recently brought in regenerative medicine for fuel all Matt. Thanks.

Yes.

And this designation allows me asking to be more responsive to our requesting insane.

Protect to expedite the regulatory process.

Concepts at the planned phase three Registrational study.

Adrienne Wilson: We've seen discussions at the FDA regarding requirements for the registrational study are currently ongoing. With regard to the current study status, patient 11, the fifth and final patient treated in three 13-dose cohorts, is now being dosed. Treatment of these five high-dose COVID-4 patients completes our Phase 1-2 trial enrolment commitment to Pfizer. As announced earlier, the transfer of the SD55 manufacturing process from Sangamo to Pfizer has already been initiated. Pfizer is currently progressing the CMC work on schedule with a commercial process that is now being scaled up to 2,000 liters.

But you have discussions with the FTC reporting requirements for the Registrational study the current young sorry.

With regards to the current studies basis patients unless I missed it.

Oh patient treated in three starting first cohorts.

Insiders.

Treatments at this point fives high dose cohort four patients complete.

Phase one two trial enrollment.

Finds out.

Well its announced idea what transpired, yes, the five C manufacturing process from secondary to find stuff has already been initiated.

FICA is currently progressing the CMC work on schedule with the commercial process, it's now being scaled up to 2000 retail.

Adrienne Wilson: We look forward to working with Pfizer on the registrational study and are very excited to see the program moving forward into late-stage development. And we've been informed by Pfizer that their lead-in study for the registrational phase 3 has already been submitted to clinicaltrials.gov and is expected to post in the coming days. So in summary then, the combination of achieving factor VIII activity levels in the high normal range, the rapid kinetics, and the durability of the factor VIII response observed so far in patients treated at the lower doses, as well as the relatively low intra-cohort variability in the context of zero bleeding events and the complete elimination of exogenous factor VIII usage in patients treated at the highest dose, suggests to us that we have the opportunity to move forward into late stage development with potentially differentiated haemophilia A gene therapy that could have a meaningful clinical impact for patients with haemophilia A.

We look forward to working with flights on a Registrational study I'm very excited to see the program moving forward into late stage development.

And we have been informed by flying the lesion studies Registrational phase three it's already been submitted to clinical trials Dot com.

And expect to post.

In the coming days.

So in summary, then the combination of determining factor IX activity levels in the height normal range erratic Tonight and mature.

Perfect Great response, so far in patients treated lumber prices. It's one it's the run its a filler trickle who variability.

In the context of meeting their friends and the competes elimination of exogenous factors usage in patients treated.

Hi, guys suggests to us.

So we have the opportunity to move forward into late stage development with potentially differentiated hemophilia gene therapy that could have a meaningful clinical impact the patients with hemophilia Ray.

Especially as mentioned by sending our recent positive experience best be five to fight. This helps inform the development of a hernia and as seen on T zero type, reaching three program, which is our next gene therapy to Ansible clinic.

Adrienne Wilson: As mentioned by Sandy, our recent positive experience with SP525 has helped inform the development of our wholly owned ST920 Fabry gene therapy program, which is our next gene therapy to enter the clinic. We believe that our considerable know-how in AUV process engineering, AUV delivery, and gene therapy dosing that we've obtained from the ongoing SB525 clinical trial has enabled us to design a Fabry gene therapy that has the potential to deliver a meaningful clinical impact to patients. And I'm happy to say that our clinical operations team has recently activated the first two clinical study sites. We expect to enroll the first patient into this STAR study later this year, and we look forward to providing further progress updates to you in due course. I want to move on briefly now and to update you on some of the other programs.

When we believe well consider full know how you see that.

Engineering, maybe deferring.

She repeat dosing.

From the ongoing SP five few fights clinical trial.

This enabled us to decide this therapy gene therapy. This the potential.

A meaningful clinical impact patients.

To say that our clinical operations team has recently activated.

Two clinical study sites.

Two enrolled the first patients into this study later this year.

When you look towards providing the purpose, it's two years into course.

I want to briefly move on now to update you on some of the other programs.

Adrienne Wilson: And first, with regard to the ST400 Thales study, which you'll remember is our investigational gene-edited cell therapy study in beta-thalassemia, which is partnered with Sanofi, and two patients have to date been treated in that study. Treatment of a third patient is imminent, and a fourth patient has recently entered the study. We anticipate completing enrolment in the SPARLAY study later this year, with a total of six patients approved. As a reminder, TFAR-BASE is enrolling patients with severe transfusion-dependent beta-thalassemia with either a B0-B0 or a non-B0-B0 genotype, and they have had at least eight documented red blood cell transfusion events per year in the two years prior to screening. We expect to have preliminary data available for this study by the end of the year. It's important to note that the collective evidence from other stem cell studies suggests that autologous stem cell transplants like SB400 require long-term data of at least a year and data from multiple patients before a treatment effect may be adequately understood. I'm going to move on now to a self-therapy portfolio.

First with regard to the S. T 400, falling study, which you remember is our investigational gene habits. So therapy study in DC senior which Uh huh.

Sanofi.

C patients being treated in America, let me.

Treatments.

Patient awareness and the fourth patient has recently entered into the study.

Yes.

Completing enrollments at the start of the study later this year.

Total of six patients accrued.

As a reminder, all basis enrolling patients with severe problems.

Pizza thalassemia, because if I'd repeat erode the zero Werent lumpiness, there I'd be zero gene at site near or at least a documented red blood cell transfusion failure.

Yes, he is processed screening.

Preliminary states were favorable for this study by the end of the year.

So no cut backs of evidence from other stem cell studies suggest an autologous stem cell transplants like before great for quite a long time, thanks Robin yes.

Data from multiple patients before treatment effect.

Yes. Thanks.

We will now to a cell therapy portfolio.

Adrienne Wilson: We currently remain on track to file the CTA for our CAR-T reg, TX200, in HLA-A2 mismatch kidney transplantation later this year, and the tech transfer to our CMO is sad to state is nearly complete. This trial is important to us as we believe it will be the first CAR T-Rex cell therapy to ever be tested in humans. This milestone event will represent yet another first for Sangamo, and it will comprise an important catalyst as we believe that the TX200 program will play a key role in establishing a human proof of concept for the safety and therapeutic viability of CAR Tregs in general. Now, if successful, it promises to pave the way for the broader application of CAR T-Rex to other medically and commercially significant autoimmune and inflammatory conditions. And lastly, Kite, the Giyad company, is planning to initiate a clinical study of Kite-037, which is an allogeneic anti-CD19 CAR T-cell product, in 2020.

We currently remain on track to follow the CJ for car T. Reg TX 200.

Actually the two mismatch kidney transplantation later this year.

And the tech transfer Torsiello, yes, I'm happy to say the complete.

This trial is important to us as we believe it will be the first car T Reg cells therapy to ever be tested in humans.

Small.

Will represent yet another first for thinking about it.

I never comprised import tariff for that is we believe that the tips to lunch program will play a key role in establishing a human proof of concept safety and therapeutic five affinity for car T regs in general.

No.

This fall it promises to pave the way for the broader application of car T. Rex. He was admitted clean commercially significant also view.

Summitry implications.

But long sleek high cap company is planning to initiate a clinical study of quite serious read seven which is the other generic anti cdnineteen car T cell products in 2020.

No no.

Adrienne Wilson: Moving on now to our in vivo genome editing program, which I believe has the potential, if successful, to eventually redefine genomic medicine. We've previously mentioned that we plan to open a new MPS2 study that utilizes our second generation albumin locus positive ZFNs that incorporate engineered modifications both to the zinc finger protein alpha helix recognition domains and also to the FOC1 nuclease fragments as well as the expression process In cellulose studies, these upgraded reagents have exhibited substantially improved gene editing activity.

So our in vivo genome editing program, which I believe has the potential if successful. So eventually you redefine genomic medicine.

We previously mentioned we plan to open a new MTS to study utilizes our second generation albumin locus targeted ZFN that incorporate engineered modification, but there's anything approaching healthy index recognition domain.

And also to the spoke quite unique taste fragment, that's why the expression of the status.

In setting the studies these are great get reagents that exhibits insights to improve gene editing simplicity.

Adrienne Wilson: And in recent months, we've identified several additional potential improvements that may further enhance the potency of our in vivo genome editing platform. Now, each of these is anticipated to enhance the delivery of Fink's fingers into hepatocytes, which we believe is the rate-limiting step that must be overcome to achieve clinical and meaningful levels of editing. And as Santa mentioned earlier, we've gained important insights into our AV6 delivery vehicle through our various clinical studies, including ESB525 and hemophilia A, where we observed significant increases in efficacy above a defined vector dose threshold when the doses increased from the 1E13 to the 3E13 dose level. This may be seen clearly on slide 16. And we believe that this suggests that AV6 will be an effective delivery vehicle in the in vivo setting once the critical intracellular vector concentration has been achieved.

We've identified several additional attached to improve further enhance the potency.

Vivo gene editing platform.

Each of these is anticipated to enhance the delivery the same thing doesn't suit.

The site, which we believe is that right.

It seems that there must be overcome sort achieve clinical meaningful levels of advertising and expense mentioned earlier these days.

These insights into our 86 delivery vehicles to our various clinical studies, including yes. These parts you Fourteenthree programming hemostat here right. So significant increases in efficacy, but let's define expected those thresholds. When does this increase from 13 to the street.

Lateral.

This may be seen clearly on slide 16.

We believe that May suggest the 86 will be an effective delivery vehicle in vivo setting what's the critical interest.

That's a concentration has been achieved what we already know prepared in vitro and in vivo preclinical studies. They think things are extremely efficient genome editing.

Adrienne Wilson: Now, we already know from both in vitro and in vivo preclinical studies that Fink's fingers are extremely efficient genome editors once sufficient intracellular levels have been obtained. And this understanding, combined with our knowledge of the AV6 threshold, has led us to consider several complementary methods for further increasing the efficiency of hepatocellular transduction. The key measures under consideration are as follows.

Mission infrastructure levels have been attained.

Despite being combined with our knowledge of the 86 thresholds.

The slots to consider several complementary metric further increasing efficiency and surpassed the foreseeable troms option.

Keith its under consideration are as follows.

Adrienne Wilson: First, increasing the total dose of administered AV, which is supported by current safety experience. Second, adjusting the ratio of the zinc fingers to the donor transgene to increase the concentration of each zinc finger-containing AV species. And third, engineering AV6 for enhanced transduction efficiency. And finally, deploying our next generation albumin locus construct with updated zinc fingers to improve genome editing precision, efficiency, and specificity. We're currently in the process of planning and initiating several new pre-clinical studies to evaluate these options, and based on our current assumptions, including the timeframe to manufacture the new AV6, we believe that this program will be in the clinic by the end of 2020. We will update investors on this timing as and when we know more. And I'd now like to turn the call over to our Chief Technology Officer, Ed Reifart, who will provide a pre-clinical and technology update.

Increasing the total size that administered aging, which is supported by current safety experience second the trusting the ratio, but there is I think there was to be turned the troms Jane.

Chris the concentration with each thing.

88 feet spacing.

Right.

At Charing 86 sprint transduction efficiency.

Finally to properly.

Our next generation of human rights as constructs with updates instinct is to improve genome editing precision efficiency.

Specificity.

We're currently in the process of talking in initiating several new preclinical studies to evaluate these options and based on our current assumptions, including the timeframe. So manufacturing Yeah 86, we believe that this program will be in the clinic by the end of 2020.

Well Peyton fast is on this timing as to when we know more.

I'd like to turn the call over to our Chief Technology officer at reasonable who'll provide a preclinical and technology I'll say.

Ed Rebar: Thank you, Adrienne, and good afternoon, everyone. At Sangamo, one of our foundational and most enduring commitments has been to advancing the science of genomic medicine. We feel strongly that the most impactful medical advances result not only from the skillful use of current knowledge but also from the application of new capabilities and insights developed through innovative research. This past quarter, we published two manuscripts that exemplify this philosophy and that demonstrate how scientific advances can enable new therapeutic opportunities. For my comments today, I will provide a brief overview of each. I hope that you will be as excited by their implications as I am.

Thank you Adrian and good afternoon, everyone.

Second one of our foundational and most enduring commitment has been to advancing the science of genomic medicine.

We feel strongly that the most impactful medical advances results not only from the scope we use a current knowledge, but also by the application of new capabilities insights develop through innovative research.

This past quarter, we published two manuscripts that exemplify this philosophy.

And that demonstrate how scientific advances can enable new therapeutic opportunities.

For my comments today I will provide a brief overview of each I hope that you will be as excited as I am but other applications.

I'll begin by describing the work of my colleague, Jeff Miller, who has developed a fundamentally new strategy for optimizing the specificity of gene editing Nucleases.

Ed Rebar: I'll begin by describing the work of my colleague, Jeff Miller, who has developed a fundamentally new strategy for optimizing the specificity of gene-editing... This work, titled Enhancing Gene Editing Specificity by Attenuating DNA Cleavage Kinetics, was published just this last week in Nature Biotechnology. In the paper, Jeff and colleagues showed that zinc-finger nucleases may be optimized for highly specific function via the novel approach of engineering their catalytic domain to slow down its cleavage rate. In pursuing this approach, they identified single residue variants of the catalytic domain that could fully preserve on-target activity while globally suppressing off-target cleavage. By combining these substitutions with others within the zinc fingers at 2 DFINITY, Jeff developed ZFNs for a therapeutic target gene, T-cell receptor alpha, that could mediate essentially complete editing with no detectable off-targets under highly sensitive assay conditions with a median background signal of less than 0.1%. This work has substantially improved our ability to rapidly engineer highly specific ZFNs for clinical use.

This work titled enhancing gene editing specificity by Attenuating DNA cleavage kinetics was published just this last weekend victory biotechnology.

In the paper jumping colleagues showed that some finger nucleases, maybe optimized for highly specific function by the novel approach of engineering, the catalytic domain to slow down its seepage rate.

In pursuing this approach just identified single residue variance of the catalytic domain that could fully preserved on target activity globally suppressing off target cleavage.

By combining these substitutions with others within zinc fingers at to DEFINITY, just develop ZFN funds for a therapeutic target gene T cell receptor alpha that could media is essentially complete editing with no detectable off targets under highly sensitive assay conditions.

He and background signal at less than 1%.

This work is substantially improved our ability to rapidly engineer highly specific see offense for clinical use.

Ed Rebar: More generally, the principles that Jeff has elucidated will likely find broad utility beyond the field of gene editing for optimizing the performance of other engineered protein systems. In the second paper, my colleague Brian Zettler established a new approach for selectively eliminating expression of the pathological protein species in Huntington's disease. This fatal neurodegenerative condition is caused by a dominant gain-of-function mutation comprising an expanded triplet repeat in the Huntington gene. Brian's article titled, Allele-Selective Transcriptional Repression of Mutant HTT for the Treatment of Huntington's Disease, was published in the July issue of Nature Medicine. In the paper, Bryan and colleagues showed that they could selectively eliminate the expression of disease alleles by the direct targeting of the zinc finger repressor proteins to the expanded triple repeat.

More generally the principles that Chuck as elucidated will likely find God utility beyond the field of gene editing for optimizing the performance of other engineered protein systems.

And the second paper my colleague, Brian Sitler established a new approach for selectively eliminating expression of the pathological proteins species and huntingtons disease.

This fatal neuro degenerative condition is caused by a dominant gain of function mutation comprising expand the triplet repeat in the Huntington gene.

Brian's article titled a wheel select two transcriptional repression you sent H T T for the treatment of Huntington's disease was published in the July issue of nature Medicine.

In the paper, Brian and colleagues show that they can selectively eliminate expression of disease, what wheels by the direct targeting of the zinc finger repress or proteins to the expanded triplet repeat.

Ed Rebar: In pursuing this approach, Brian's team identified zinc finger protein repressors that exhibit cooperative recognition of the expanded repeat, which enabled a high degree of allelic discrimination. In patient-derived fibroblasts and neurons, these ZFPs selectively repressed disease-causing alleles over a 100-fold dose range while preserving expression of the healthy wild-type alleles. An important component of this work was its characterization of the repressors in preclinical disease models, which was performed in collaboration with the Cure Huntington's Disease Initiative Foundation. Using several different mouse models, Sangamo scientists and our collaborators showed that delivery of repressors to the CNS, the central nervous system, could increase levels of neuronal markers, improve behavioral and electrophysiological deficits, and reduce levels of Huntington aggregates and other molecular correlates of the disease. More generally, this study has established transcriptional repression as an effective approach for eliminating protein drivers of central nervous system disease. This is significant, given that many neurodegenerative conditions appear to be driven by apparently expressed or misfolded peptides whose genetic source may be known, but whose exact molecular identity may be difficult to ascertain among the diversity of different isomers, conformational variants, and post-translationally modified products that may be generated from any given gene.

It pursuing this approach Brian's team identified zinc finger protein pressures that exhibited co-operative recognition of the expanded repeat which enabled the high degree it'll be what discrimination.

Patient derived fiberglass and they're all seasons, yet piece selectively repressed disease, causing a wheels over 100 fold dose range, while preserving expression of the healthy wild type of deal.

An important component of this work was this characterization that the reprocessors in preclinical disease models, which was performed in collaboration with the cure Huntingtons disease Initiative Foundation.

Using several different mouse models, sangamo scientists and our collaborators showed that delivery every crushers CFS central nervous system could increase levels and their own markers improve behavioral and electrophysiological deficits and reduced levels of Huntington aggregates and other molecular correlates for the disease.

More generally the study has established transcriptional repression as an effective approach for eliminating protein drivers of central nervous system disease.

This is significant given that many neurodegenerative conditions appear to be driven by apparently expressed or misfolded peptides, whose genetic source, maybe known but it was exact molecular identity, maybe difficult to ascertain among the diversity of different isom isomers conformational variants and post translational modified products that may be generated from any given gene.

The ability to sidestep this complexity violent by a gene repression provides a powerful means reducing technical risk as compared to protein targeted technologies, such as monoclonal antibodies and small while these trucks in situations, where the exact pathological species is unknown.

Our partner for this program Takeda is currently working with Sangamo on further engineered designs to selectively target the mutant Huntington Gene every Christmas transcription.

Ed Rebar: The ability to sidestep this complexity by gene repression provides a powerful means for reducing technical risk as compared to protein-targeted technologies, such as monoclonal antibodies and small-volume drugs, in situations where the exact pathological species is unknown. Our partner for this program, Decada, is currently working with Sangamo on further engineered designs to selectively target the mutant Huntington gene and repress its transcription. We understand that Takeda will evaluate the potential clinical candidate for the treatment of Huntington's disease in preclinical IND-enabling studies.

We understand that Takeda will evaluate the potential clinical candidate for the treatment of Huntington's disease, and preclinical idea enabling studies.

In summary, then this was in a typical quarter for a second to science with major publications in two high impact journals.

I'm very proud of these achievements by our colleagues in collaborators I look forward to providing further updates as our other research programs mature.

I'll now turn the call over to Mcdavid for review of our second quarter 2019 financial results David.

Thank you Ed.

I'm filling in for our interim CFO , Andy VP of corporate strategy, Stefan will sell who has obligations overseas today and is consequently, unable to join us on the call.

Ed Rebar: In summary, then, this was an impactful quarter for Stangalous Science, with major publications in two high-impact journals. I'm very proud of these achievements by our colleagues and collaborators and look forward to providing further updates as our other research programs mature. I'll now turn the call over to McDavid for a review of our second quarter 2019 financial results. Thank you, Ed.

Detailed financial statements were included in the press release that we issued this afternoon and the Form 10-Q that we filed just prior to this call.

Accordingly.

Let me address the highlights.

Revenues for the second quarter ended June Thirtyth, 2019 or $17.5 million.

Fair to $21.4 million for the same period in 2018.

The decrease was primarily due to a decline of 3.7 million in revenues related to our agreement with Pfizer and was due to a change in an estimate as a result of the expansion of the project scope of the hemophilia a collaboration.

McDavid Stilwell: I'm filling in for our Interim CFO and EVP of Corporate Strategy, Stephane Boissel, who has obligations overseas today and is consequently unable to join us on the call. Detailed financial statements were included in the press release that we issued this afternoon and in the Form 10-Q that we filed just prior to this call. Accordingly, I will only address the highlights.

As anticipated operating expenses increased in the second quarter ended June Thirtyth 2019.

Reflecting the company's growth through the acquisition of Te XL.

Increased U.S. head count in support of growth of the preclinical pipeline and clinical development programs.

McDavid Stilwell: Revenues for the second quarter ended June 30, 2019, were $17.5 million, compared to $21.4 million for the same period in 2018. The decrease was primarily due to a decline of $3.7 million in revenues related to our agreement with Pfizer and was due to a change in an estimate as a result of the expansion of the project scope of the Haemophilia A collaboration. As anticipated, operating expenses increased in the second quarter ending June 30, 2019, reflecting the company's growth through the acquisition of TXL, increased U.S. headcount in support of growth of the preclinical pipeline and clinical development program, and the Manufacturing Readiness Act. Total operating expenses for the second quarter ending June 30, 2019, were $51.1 million, compared to $40.6 million for the same period in 2018.

And manufacturing readiness activities.

Total operating expenses for the second quarter ended June Thirtyth 2019.

The $1.1 million.

Compared to $40.6 million for the same period in 2018.

Research and development expenses were $36.5 million for the second quarter 2019, compared to 29.3 million for the same period in 2018.

The increase in R&D expense was primarily due to manufacturing and clinical trial expenses.

General and administrative expenses were 14.6 million for the second quarter of 2019 compared to 11.3 million for the same period in 2018.

The increase was primarily due to increased compensation cost due to headcount growth and increased facility expenses related to our new Brisbane, San Francisco Bay area facility.

Construction of our in house manufacturing capability in Brisbane is proceeding on schedule and we expect to commence GMP qualification procedures early next year.

As of June Thirtyth 2019, the company had cash cash equivalents and investments of $415.3 million.

As for our financial guidance for 2019, we continue to project operating expenses of $210 million to $220 million for the year.

McDavid Stilwell: Search and development expenses were $36.5 million for the second quarter of 2019, compared to $29.3 billion for the same period in 2018. The increase in R&D spend was primarily due to manufacturing and clinical trial expenses. General and administrative expenses were $14.6 million for the second quarter of 2020, compared to $11.3 billion for the same period in 2020. The increase was primarily due to increased compensation costs due to headcount growth and increased facility expenses related to our new Brisbane-San Francisco Bay Area facility. Construction of our in-house manufacturing capability in Brisbane is proceeding on schedule, and we expect to commence GMP qualification soon.

Regarding our cash runway.

Need to protect the current cash cash equivalents and investments.

Provide funds for operations through year end 2021.

And with that I'll now.

I'll turn the call back to Sandy for some closing remarks document David.

I would like to close by saying that we're very pleased with the various accomplishments this quarter and excited about the future.

Clinical data from our Humane gene therapy candidate continue swimming promising.

We made significant process progress process and initiating the transfer of the clinical program and Pfizer and progressing Registrational trial discussions with regulators.

I swear is committed to taking the study into late stage development and we anticipate this will result in our first license product.

Well he may ditto portends, well for our gene therapy program in foundry for which the first clinical site. This activity this quarter.

We're also probably tougher to publications nature from the journals help to find the pieces apart.

Its next generation ZFN genome editing.

McDavid Stilwell: Early next, As of June 30, 2019, the company had cash, cash equivalents, and investments of $450.3 million. As for our financial guidance for 2019, we continue to project operating expenses of $210 to $220 billion, based on our cash runway. We continue to project that current cash, cash equivalents, and investments should provide funds for operations through year-end 2021. And with that, I'll now turn the call back to Sandy for some closing remarks. Thank you, McDavid.

No Street exclusive selectivity approaching regulation platform that enables us to constantly interest challenging CNS indications of high unmet medical need.

Let's take large patient populations.

And I have to teach provides intractable using conventional medicines.

We look forward to continuing to show updated teeth into progressing new programs based on our discoveries into the clinic as part of our X weave upon Indies.

As mentioned we are in parallel continuing to push ahead with our strategy and she turned mix in people genome editing trough dress is perhaps the most challenging area of gene editing.

It's important that we about the potential improvements turning people genome editing technologies, which is we believe the first step on the journey to successful in people gene editing.

Alexander D. Macrae: and excited about the future. Clinical data from our HeMe gene therapy candidate continues to look promising, and we've made significant progress in initiating the transfer of the clinical program to Pfizer and in progressing registrational trial discussions with regulators. Pfizer is committed to taking the study into late stage development, and we anticipate that this will result in our first licensed product. The favorable He-May Data portents well for our June therapy program in February, for which the first clinical site was activated this quarter.

Defining the future of clinical medicine.

We look forward to updating you on the key capitalism milestones ahead.

Well I'd like to thank you once again for joining us on the call today.

Turn to your questions.

Right.

Thank you Sir.

As a reminder, ladies and gentlemen to queue up for a phone question. You May Press Star then one on your Touchtone phone. If your question has been answered but wish to remove yourself from the phone queue. You may press the pound key.

One moment for questioners to queue.

Our first question in queue will come from the line of going with Barclays. Please go ahead. Your line is now open.

Alexander D. Macrae: We're also proud of our two publications in Nature Family that help define the basis of our enhanced next-generation ZFN gene editing platform and illustrate the exquisite selectivity of our gene regulation platform that enables us to confidently address challenging serious indications of high unmet medical need that affect large patient populations and have to date been intractable using conventional medicines. We look forward to continuing to show updated data and to progressing new programs based on our discoveries into the clinic as part of our next wave of INDs. As mentioned, we're, in parallel, continuing to push ahead with our strategy to initiate our next in-person genome editing trial that addresses perhaps the most challenging area of gene editing. It's important that we evaluate the potential improvements to our in vivo genome editing technologies, which is, we believe, the first step on the journey to successful in vivo gene editing that will help define the future of clinical medicine. We look forward to updating you further on the key capitalists and milestones ahead. We'd like to thank you once again for joining us on the call today. We'll now turn to your questions.

Thank you very much for taking my questions and congratulation on that.

Oh the progress so just first question regarding the data.

The you mentioned like for Q.

Yes Bose yes.

Hemophilia, a and B that EMEA all will have I think you should we expect this to.

At the Ash.

And then we if yes in a really meaningful.

Disclosure in the abstract.

Hi, gentlemen, David Thanks for the question.

So we're not going to commit to that conference until we've actually had our abstracts accepted.

At the conference, but that would be a logical place too.

To to present the data.

And we are emphasizing Gina the patience.

Particularly patient the patient three or four would have very little data acquired by that time by the end of the quarter. This view seems like from the Blue card experience. The speed take some time before we fully understand the benefit to the patients you are referring to beta policy. This itself.

Regarding be reflecting it do you.

Anymore, because you do.

We haven't discussed the patients that were enrolling.

Okay, and then just a quick question regarding.

Hemophilia, a and b.

Operator: Thank you, sir. As a reminder, ladies and gentlemen, to queue up for a phone question, you may press star then 1 on your touchtone phone. If your question has been answered or you wish to remove yourself from the phone queue, you may press the pound key. One moment for questioners to queue.

These.

Program.

So just wondering you know for the sector eight level.

Now when we look at the initial solution in place at the level continue to increase.

Just wondering if you have any scientific mechanism so understanding that explain that.

Operator: Our first question in queue will come from the line of Yina Wang with Barclays. Please go ahead. Your line is now open.

Clearly the fact that he level in the first six months.

I'm not sure if we see the I'm looking I'm looking at the.

Huidong Wang: Thank you very much for taking my questions and congratulations on all the progress. So just first question regarding the data update: you mentioned 4Q this year, both hemophilia A and beta thalassemia, but we'll have updates. Should we expect this at ASH? And if so, will we see some meaningful disclosure in the abstract? Hi Gina, it's McDavid. Thanks for the question. So we're not going to commit to that conference until we've actually had our abstracts accepted at the conference, but that would be a logical place to present the data.

The graph push slight numbers that.

Number six.

16, we feel we feel we can both the.

The crew majestic, both the linear and the local arithmetic that we said.

10 to 12 weeks the or.

Plateauing out.

Do you see.

Still increasing to appoint.

I see so like if you look at slide 15, that's my speech at CNN.

Maybe six to also on the left side kind of.

McDavid Stilwell: And we're emphasizing, Gina, that the patients, particularly patients three or four, would have very little data acquired by that time, by the end of the quarter, and that it seems like, from the Blueprint experience, that this may take some time before we fully understand the benefits.

So we will see like so you are expecting to ship plateau out right. So basically later this year, if we see longer follow up we should see the protein levels should stabilize Iran, and if some of the fleets.

McDavid Stilwell: Are you referring to beta thalassemia? Yes. Regarding beta thalassemia, did you enroll any more beta 0, beta 0 patients?

Chronic Jack assay or.

Well my speech I think it would be like if we're being 200 to 200 like $1.50 to tighter range right.

Unnamed Speaker: We haven't discussed the patients that we're enrolling yet.

Unnamed Speaker: Okay, and then just a quick question regarding the hemophilia A and the Fabry disease programs. So, just wondering, you know, for the factor A level, when we look at the initial first three patients, it seems like the factor A level continues to increase. Just wondering if you have any scientific mechanisms or understanding that could explain the continued increase of the factor A level in the first six months.

I'm going to pass on to it.

In a moment, but we focus on the cryogenic assay and more importantly, we we just need to let the street. Please over the course of figure to give everyone comfort and confidence in the levels that were achieving 18, just yeah. I mean, just to say to you know when I look at the data.

Well never lets just say its flat, but it's looking a little bit light up to me.

Unnamed Speaker: I'm not sure we see that. I'm looking at the graph. Which slide number is it? That's number 16. 16. We feel, looking both at the chromogenic, both at the linear and the logarithmic, that within 10 to 12 weeks they are plateauing out. Do you see it still increasing at that point?

When you look at it closely.

Next up and down around kind of main if you like preoccupation with it and that's the kind of an intrinsic.

Probably a biological variability of having this.

Mo expression.

But I wouldn't rule.

Leased but only because the data.

I'm not seeing.

You know per term I'm seeing a stabilization within the high normal range.

Unnamed Speaker: I see so like if you look at slide 15 that's the one stage assay, and then maybe 16 also on the left side, you know kind of okay, so we will see, like, later this year if we see longer follow-up, we should see the protein level should stabilize around 150 if we're using a chromogenic assay or one stage assay will be like within 200 to 200, like the 150 to 200 range right.

So sorry.

That's right correct churn as far as I said.

They kind of stabilized out and that's what I'm, saying.

Of course some.

By the end of the year you know, we'll have a minimum of six months data for approval will patients in that cohort some ups around the year for the one he was first treated so from that but that's how I see it as you know Myron.

Great and then one last very quick question regarding the fabry disease.

Based on the hemophilia, a clinical data and also preclinical data for both hemophilia and fabry.

Unnamed Speaker: We focus on chromogenic asthma, and more importantly, we just need to let this data play out over the course of the year to give everyone comfort and confidence in the levels that we're achieving.

No.

Could you remind us your first those who fabry disease and are you aiming to.

Adrienne Wilson: Yeah, I mean, just to say, Gina, when I look at the data, I mean, one never likes to say it's plateaued, but it's looking a little bit like that to me. When you look at it closely, it kind of moves up and down around a kind of mean, if you like, for each patient. And that's a kind of intrinsic, probably biological variability of having this epithermal expression.

Yeah.

To achieve minimal.

But effective minimal.

Within a minimal.

And go with the flow.

If those but they didn't therapy.

She died we haven't said what the dose wouldn't be so.

We will reveal more of that study involves I'll just I'll just say one thing. This is something we have talked about the match between the two.

You, probably remember Katrina, we present in some states are asked GCP.

Adrienne Wilson: But overall, at least when I look at the data, I'm not seeing an uptrend; I'm seeing a stabilization within the high normal range. So this is kind of like, you know, a complete correction as far as I can see it, you know, and they've kind of stabilized out. And that's what I'm seeing. And of course, by the end of the year, you know, we'll have a minimum of six months of data for all patients in that cohort and up to around a year for the one who was first treated. So we'll know better. But, you know, that's how I see it, Gina, at the moment.

In the current code.

No power market, which is the GE they knocked out.

And these mice like al forgot activity may accumulate large amounts of substrate costs for centuries, and we used the same 86, including the human Gionee specific promoter was manufactured in the exact same way.

The basin clinical scale production method that were currently using.

You saw that yes, we can.

16 front falls.

Adrienne Wilson: And then one last very quick question regarding Fabry disease. So, based on the hemophilia A clinical data and also preclinical data for both hemophilia A and Fabry, could you remind us your first dose for Fabry disease? And are you aiming to, you know, achieve minimal effect within a minimal therapeutic window, the low effective dose for gene therapy?

Increasing.

Oh, I forgot I activists east Ricky.

Britney pronounced expression so.

As we said previously we were expecting the all the learnings.

That we.

We've taken from our work in hemophilia trite, but appeal the grade really is.

I think so for example, if housing therapy Craig.

Adrienne Wilson: Do you know? We haven't set what that dose would be, so we will reveal more of that as the study evolves.

Im going to expecting those learnings will.

Actively transfer the factory and.

Adrienne Wilson: I'll just say one thing, though, and this is something we have talked about. And actually, you probably remember, Gina, we presented some data at ASGCT using the GLECO knockout model, which is a GLA knockout. And these mice lack alpha-gal activity, and they accumulate large amounts of substrate in the plasma and tissues. And then we used the same AD26 encoding human GLA with a lipospecific promoter, and it was manufactured in the exact same way, you know, based on the clinical scale production method that we're currently using. And what we saw there is that we got a 1,500-fold increase in alpha-gallate activity. So, really, really pronounced expression.

Preclinical data that we saw in the model.

Turning to a large extent makes us confident that that's the case and we're also of course in that same month dataset that we presented them GCC showed that we see the substrate reduction in all the key tissues.

Oh, yes.

And.

So we are really confident about where we're going here in February .

Thank you for your question.

Thank you.

Thank you. Our next question in queue will come from the line of Hawaii Raycroft with Jefferies. Please go ahead. Your line is now open.

Hi, everyone. Good afternoon, and thanks for taking my questions. So.

Am I think Adrian mentioned earlier that the Pfizer had submitted elite in study for the phase three two clinical trials I got it. So I'm just wondering if you could talk more about that Saturday and what the purpose of it is.

Adrienne Wilson: So as we said, you know, just previously, we're expecting that all the learning that we've obtained from our work in hemophilia rate, which I hope you'll agree, really is an exemplary example of how gene therapy should look, right? And we're hoping and expecting that those learnings will effectively transfer to Fabry. And the preclinical data that we saw in the glyco models, you know, to a really large extent, makes us confident that that's the case. And we also, of course, in that same data set that we presented in ASGCT, showed that we see substrate reduction in all the key tissues, that liver, heart, and kidney. So we're really confident, you know, about where we're going here in fabric. Thank you for your questions.

And as follow up for the Phase three design what are some of the most likely scenarios that could happen with the phase three and how likely is it that an accelerated approval path will be an option.

We.

So Martin Thank you for your question, we rely on our friends at Pfizer to talk with US we had hoped to submit to control. So a couple things would be likely know and it's in the process.

And you'll be able to see more of that when it when it becomes visible on the web site.

They won't be the ones, who want to talk about the phase three study the like costs are excited by the data and I think the the fact that they are initiating this you can study is a sign of their commitment to this.

Adrienne Wilson: Transcribed by https://otter.ai

Yes, I said that we were actually expecting that pose three even today actually they submit giving to us.

Operator: Thank you.

Maurice Thomas Raycroft: Thank you. Our next question in queue will come from the line of Maurice Raycroft with Jeffries. Please go ahead. Your line is now open.

Can you also talk a couple of states.

We literally expect here.

No I would say.

Got it and as far as that the Registrational study go is there any thoughts on.

Alexander D. Macrae: Hi, everyone. Good afternoon, and thanks for taking my questions. So, I think Adrienne mentioned earlier that Pfizer had submitted a lead-in study for the Phase 3 to ClinicalTrials.gov, and so I'm just wondering if you could talk more about that study and what its purpose is, and as a follow-up to the Phase 3 design, what are some of the most likely scenarios that could happen with the Phase 3, and how likely is it that an accelerated approval path will be an option there?

Whether that would look similar to Iraq's.

Phase three study or any perspective, there would be helpful.

We have an agreement and these kind of partnerships you have an agreement to that he talks about bought and so the preferred that we don't talk about a newly post discussions, but I just want to reassure uptick when we speak to all of our partners on a regular basis, we've written the student commit to use in clinical development committees.

And we are.

Pfizer and excitement over the hemophilia a results, we're very aligned and where this is going and doing everything to help them overcome please.

Alexander D. Macrae: We had hoped that the submitted ClinTrans.gov thing would be live by now, and it's in the process, and you'll be able to see more of it when it becomes visible on the website. They will be the ones who talk about the Phase 3 study. They, like us, are excited by the data, and I think the fact that they are initiating this lead-in study is a sign of their commitment to this.

Got it okay and I'm just wondering if you.

Now that you're you're talking more about the kite 037 program and Dan.

That's.

Likely to advance in 2020, if you can just compare and contrast.

How that would look versus other allogeneic approaches out there.

Alexander D. Macrae: Yeah, and as I said, we're actually expecting that to post literally even today. They submitted it to clinicaltrials.gov a couple of days ago, and we literally expect it to post next Wednesday.

So so again.

The agreement with Chi Gilead does that they talk about that piece. So the we have an ongoing relationship with both.

Through kite with getting out where we are probably the editing capabilities to help them.

Alexander D. Macrae: Got it. And as far as the registrational study goes, any thoughts on whether that would look similar to Valarock's Phase 3 study or any perspective there would be helpful?

Selling the most effective other generic.

Assets.

Alexander D. Macrae: We have an agreement, and in these kinds of partnerships, you have an agreement about who talks about what, and so they prefer that we don't talk about it, and they leave those discussions. But I just want to reassure everyone, we speak to all of our partners on a regular basis, we have regular steering committees and clinical development committees, and we are, with Pfizer and the excitement over the haemophilia A results, very aligned with where this is going and doing everything to help them move forward promptly.

And when they get into the I'd station beyond that I'm sure they will.

Ultimately talking about anything that's been done to me this effect.

Understood. Okay, and then maybe the last question just on the T. XL.

Trial, if you can comment on that design and.

Number of patients that you plan on getting into that study and.

If you're going to be using donor patients for the cells there.

Any any perspective, there would be helpful.

Maurice Thomas Raycroft: Okay, and I'm just wondering if you, now that you're talking more about the CHITE 037 program and that's likely to advance in 2020, if you can just compare and contrast how that would look versus other allogeneic approaches out there.

We really haven't said much about this trial.

We will once a CTO is.

Submitted and approved unless we start to get into bhutto's more but thats a sign that the strong I really I'm, sorry, mores I can pay more helpful. With the information we're just very careful.

Alexander D. Macrae: So again, the agreement with Kite and Gilead is that they talk about that piece. So we have an ongoing relationship with both Kite and, through Kite, with Gilead, where we provide the editing capabilities to help them design the most effective allogeneic technology.

Hi, much.

How much.

Planning and.

Just like we get though to the stage.

Understood understood.

Thanks for taking my questions and I'll hop back in the queue.

Thanks.

Thank you Sir our next question in Cuba comfortable room with Cowen. Please go ahead. Your line is now open.

Alexander D. Macrae: And then maybe the last question, just on the TXL trial, if you can comment on the design and number of patients that you plan on getting into that study and if you're going to be using donor patients for the cells there, any perspective there would be helpful.

Hello. Thank you for taking my question. This is Lima on for retail.

I just want to follow up on the transfer of five to five to five there you said that it's been initiated and I was wondering if you could.

Side any more color on how long the overall tech transfer process will take and maybe any sort of timeline of when you think about start producing the product for the phase three trial. Thank you.

Alexander D. Macrae: We really haven't said much about this trial. We will, once the CTA is submitted and approved, and as we start to move into it, talk more about the design of this trial. I really am sorry, Maury, that I can't be more helpful with the information. We're just very careful about how much planning and design we give out at this stage.

I am afraid I have to refer you to my previous onshore with Maury.

Let me, let me assure you that.

We've been talking with Pfizer, but the transfer this for months if not years as we plan for high school and the two when the project moves over the whole process has become more energized by the pleasure. The thing we see in the in the results then you're talking with their dipping designing their manufacturing plan for some time so is it.

Maurice Thomas Raycroft: Okay, understood. Thanks for taking my questions, and I'll hop back in the queue.

Regent Maroon: Thank you, sir. Our next question in queue will come from Regent Maroon with Cohen. Please go ahead. Your line is now open.

Alexander D. Macrae: Hello, thank you for taking our questions. This is Lila from Re2. I just want to follow up on the transfer of 525 to Pfizer. You said that it's been initiated, and I was wondering if you could provide any more color on how long the overall tech transfer process will take.

It is seamless they have plans for the line do you transfer for the clinical trial and from a regulatory strategy.

I wish I could see more but.

And it's up to them to shoot love if you.

Okay. Thank you very much.

Alexander D. Macrae: The Bulletproof Executive, 2013

Thank you ma'am. Our next question in queue will come from the line of looking at him with Guggenheim Securities. Please go ahead your questions. Please.

Operator: Thank you for using the product in the Phase 3 trial. Thank you.

Regent Maroon: Hello, I'm afraid I have to refer you to my previous answer with Maury. Let me assure you that we've been talking with Pfizer about the transfer of this for months, if not years, as we plan for how this will look when the project moves over. The whole process has become more energized by the pleasure that they and we see in the results. They have been designing their manufacturing plan for some time so that it is seamless. They have plans for the IND transfer, for the clinical trial, for the regulatory strategy, and I wish I could say more, but it's up to them to rely on sheer luck with you.

Hi, This is actually Evan Wang on for Whitney.

First I had a question on odd.

Editing.

How can we expect.

Updates for that program or as progress Progressive do plan to share updates until it pretty called.

No.

Close enough.

Well, yes, well we'll share the.

Information as we have more specific.

Details about these plans so please stay tuned.

As we said we expect to initiate.

This next study.

Towards the end of next year.

And just to be explicit we have b.

We've already manufacture is zero and 2.2.

Alexander D. Macrae: Okay, thank you very much.

Whitney Antonin: Thank you, ma'am. Our next question in queue will come from the line of Whitney Antonin with Guggenheim Security. Please go ahead with your question, please.

But if we were to I didn't some of the additional advantages that wiki from what we have learned from.

He made.

Evan Wang: Hi, this is actually Evan Wang speaking on behalf of Whitney. First, I had a question on genome editing. How can we expect updates for that program, or as progress progresses, do you plan to share updates on the preclinical data?

The vsix it she can alert that manufacturing campaign and its really thought the trial is the the timing.

But just to step back a little from it we are very grateful for the health we've had from the.

Adrienne Wilson: Do you want to give your thoughts on that?

Adrienne Wilson: Well, yeah, we'll share the information as we have more specific details about these plans. Please stay tuned. As we said, we expect to initiate this next study toward the end of next year.

MISO little move storage disease community.

Fueling obligation to these patients to make sure that they have the best possible asset.

And well I could Russia has been going with CF and 2.0, which we we all have great belief and if I can add an extra chance for them to for this to be successful I think that's the right thing to do and I am sure. All of you on the phone would agree.

Alexander D. Macrae: To be explicit, we have already manufactured ZFN 2.0, but if we were to add in some of the additional advantages that we gained from what we have learned from He-May AAV6, it would take another manufacturing campaign, and that's really what drives the timeline. But just to step back a little from it, we are very grateful for the help we've had from the Lysolomal Storage Disease community. We feel an obligation to these patients to make sure that they have the best possible asset. And while I could rush ahead and go in with ZFN 2.0, which we all have great belief in, if I can add an extra chance for them, this will be successful.

Understood and then I had a question on content.

It seems like you said that.

Can you indicate are still kind of.

Okay working on further design I thought she asked if you see that they chose the target has that changed.

Well that's another one that is.

I'm sorry, if we lift any confusion on this keeps us to drive forward and there as we understand there in 90, enabling studies, which would suggest that the hump.

Alexander D. Macrae: And then I had a question about Huntington's. It seems like you said that you and Takeda are still kind of... Working on further designs, I thought at ASGCT that they chose a target. Has that changed?

The coupons are taking colbert.

Again, they will they will be able to talk to more about that.

Chris This is obviously a huge excitement about I'd say turret, Tim if you saw the papers that Brian most of the segments truly remarkable paper I mean it was.

Alexander D. Macrae: Oh, that's another one that is... I'm sorry if we've left any confusion on this. That's Takeda's to drive forward, and they're, as we understand, they're in IND enabling studies, which would suggest that they have, do what they're taking forward. Again, they will be able to talk to you more about that.

Binary.

Switching off but the expression of the meaningful Huntington gene, we complete presentation, the wild type deal.

I think as you know the molecular level that very similar it's a different number for Pete.

Yes, we were able to design.

Fingers.

Discriminate between various different numbers, the prepaids and I think that really speaks to the extraordinary.

It's hard to see an optionality with the platform that I cant imagine many other platform being able to deliver such a complex physician.

Evan Wang: There's obviously huge excitement about that data and, you know, I don't know if you saw the paper that Brian authored, it's a truly remarkable paper. I mean, it was almost binary, switching off of the expression of the mutant Huntington gene with complete preservation of the wild-type allele, and as you know, you know, the molecular level, they're very similar, it's just a different number of repeats, and yet we were able to design zinc fingers that could discriminate between those different numbers of repeats, and I think that really speaks to the extraordinary diversity and optionality of the platform, and I can't imagine any other platform being able to deliver such a complex solution, a solution to such a complex problem so efficiently, and it obviously opens up a load of other possibilities for us with other repeat diseases, and it's a generalized proof of concept for the remarkable behavior of these reagents that Ed and his team has managed to bring to bear on these problems of these really intractable CNS diseases, so we're really, really excited by this, as are Takeda, as you'd imagine.

First solution such a complex problem so efficiently.

And oversee opens up a lot of other possibilities for us.

Repeat diseases, and there's a chart realize proof of concept for the.

No.

Behavior. The theory these reagents and his team has managed to bring to bear on these.

Problems with Israeli intractable.

CNS diseases. So we're really really excited by it.

The key to this year's imagine.

Got it and then we have one last question.

On the partnership with tight.

Have you had any.

Regular interactions, we're having met with Christy after she scripts you know any kind of change in the partnership or.

The nature the friendship there.

So we talk regularly with the team at kite.

And weve talked with them through the base changes in the leadership and my understanding is you just started this week, so I'm I'm expecting to meet with our son.

Work at how we can work as closely together she comes with a very good reputation. So we look forward to meeting or.

Evan Wang: Got it. And then we have it.

Evan Wang: One last question. Regarding the partnership with KITE, have you had any regular interviews?

Thank you.

Thank you. Our next question comes from the line of Eric Joseph with JP. Morgan. Please go ahead. Your line is open.

Alexander D. Macrae: Regular interactions, or have you met with Christy after she's become CEO? Any kind of changes in the partnership, or... and the Nature of the Partnership.

Hey, guys. Thanks for taking the questions just a couple on the onset grazed with his team and 20 and we take a peek at the clinical trial porcelain.

Alexander D. Macrae: up there.

Alexander D. Macrae: So we talk regularly with the team at KITE, and we talk with them about the various changes in their leadership, and my understanding is that she just started this week, so I'm expecting to meet with her soon and work out how we can work as closely together. She comes with a very good reputation, so we look forward to meeting her.

Control. So I'm, just curious to get a sense of the type of.

Patient history or.

Youre seeking to recruit in the dose escalation portion in terms of.

Phenotypes and severity or mutational background and also whether you can get is full truckload were held back throughout the year T is going to factor into.

Eric Joseph: Thank you. Our next question comes from the line of Eric Joseph with J.P. Morgan. Please go ahead. Your line is open.

I guess patient monitoring post infusion.

I guess really specifically, how you're going to be delineating ofer.

Adrienne Wilson: Hey guys, thanks for taking the questions. Just a couple on Fred Reyes with ST920. We took a peek at the clinical trial post-op on clintrials.gov. I'm just curious to get a sense of the type of patient history you're seeking to recruit in the dose escalation portion in terms of, you know, phenotypes of severity or mutational background, and also whether you can at this point talk a little bit about how background ERT is going to factor into I guess patient monitoring post-infusion, I guess really specifically how you're going to be delineating alpha-GALA expression by the transgene versus any background ERT use.

Galley expression, but the transgene versus any background here to use.

Okay. So everything that was a little difficult to hear you and aging.

Did you manage to me that you know.

I think so yes.

So, yes, we think to be taking patients into the study.

Previously exposed to suffers lie more reps who call.

I'm repeating patients who've been on chaperones.

Iron.

[laughter] Fogo, so like most says Oh.

Fabry disease.

And one of three arms the key.

Parameters, which we haven't disclosed that lift truck, which which are in the protocol, but I can tell you and Joe current Cymer is one of them.

On hydro assist you I assume some so crude cars piece, yes.

Eric Joseph: So Eric, it was a little difficult to hear you, but Adrian, did you manage to make out enough?

Although.

One big one in size.

Hello.

Adrienne Wilson: I think so, yeah. So we're basically taking patients into the study who have either been previously exposed to Fabrozyme or Retrogard, and we're excluding patients who have been on chaperones, and they have to have a formal diagnosis of Fabry disease and one of three other key parameters which we haven't disclosed but which are in the protocol, but I can tell you angiokeratoma is one of them, anhidrosis, GI symptoms, So that's the that's the kind of key inclusion exclusion. We'll be looking, obviously, at safety as the key endpoint, and then we're going to be looking at plasma alpha-gallet activity as one of the key secondaries, GB3 substrate levels in the plasma, and lyso-GB3 in plasma and urine.

So it's as I said I was fighting for physical signs.

Thanks.

The property as defined by the plasma Alphacat, a lot goes and one or more of those characteristics.

That's the.

That's the kind of key inclusion and exclusion.

We'll be looking obviously at safety is Pat.

The key endpoint and then we're going to be looking at.

Plasma alphacat activity.

Hi, Sam.

The key selling drugs.

Gbpthree substrate levels.

In the plasma Lysa Gbpthree aspirin, you're in obviously you ask about yachts, he say yet what we see.

We're going to be looking at.

Yes, he frequency yes.

And we'll go after four weeks of treatment, we can be looking at.

Of course, the colon. So this is he or she is true so we see alphacat play levels.

Growing up and Gbpthree substrates and license you be three substrate, drawing down that will make the patients eligible for TV stronger for weeks and we're also obviously going to be looking at estimated Cif Paul as some referenced by the craft woman that goes in the biologic. So.

Adrienne Wilson: Obviously, you asked about ERT, so obviously, we're going to be looking at ERT frequency of use, and after four weeks of treatment, we're going to be looking at, of course, the goal, as always, is ERT withdrawal. So if we see alpha-gallet levels going up and GB3 substrates and lyso-GB3 substrate going down, that will make the patient eligible for ERT withdrawal at four weeks, and we're also obviously going to be looking at estimated GFR as referenced by creatinine levels in the blood. So I hope that answers your question. I didn't quite hear everything you said, but I'm hoping that will answer most of your questions.

There is no question I didn't quite hear everything.

I'm, hoping that will answer most of your questions.

That's great.

That's very helpful. Yeah.

Well I want to sort of curious Andy.

So I guess with all the progress you've made with.

The encouraging data that.

You bet.

Presented with by 25 in.

And.

Really before the read through validation because there just curious to get a sense of sort of the level of interest.

Well, yes every three weeks.

Eric it's very very difficult to be asked about the level of strategic interest for S. T 920.

Eric Joseph: That's very helpful actually, yeah. I'm also curious, Andy, with all the progress that you've made with the encouraging data that you've presented with 525 and really kind of the read-through validation for the vector. I'm curious to get a sense of sort of the level of strategic interest with the...

So you mean us and partnerships.

I didnt exactly how many partnerships whether it's whether at this point.

Internally high speed superior thinking about advancing that program.

Go it alone versus seeking partnerships and at what point.

British ups run the table at what point you might look to do that thank you.

So so that's an important.

Click complex structure strategic decision. We are we want to build a fully integrated company, we want to take products through to patients and eventually reach the market.

Eric Joseph: Eric is not here. Eric is in...

Eric Joseph: Eric is very, very difficult to ask about the level of strategic interest for ST920.

Alexander D. Macrae: So, you mean us in partnerships?

I see thank 20 is our lead us.

Eric Joseph: Exactly, as in partnerships, whether, at this point, just internally, how specifically you're thinking about advancing the program alone versus seeking partnerships, and at what point, if partnerships are on the table, at what point you might look to do that. Thank you.

Is wholly owned.

Just as a sign that the.

Hemophilia Epicentral do is partnered with Pfizer will bring a significant return to cycle more than many peoples wholly owned.

Ultra rare disease said petition for partnering on a common disease with hemophilia a.

Alexander D. Macrae: So that's an important and complex strategic decision. We want to build a fully integrated company. We want to take products through to patients and eventually through to the market. SC920 is our lead asset now that it is wholly owned.

And of course, there's many people interested in a fabric program.

We are at this moment come into to try things over to finding the clinical effect at this.

Hopefully bring it to patients.

And to us in a site as well on our partnering we are very pleased with the partnerships, we have with Pfizer Sanofi galea to know with Takeda.

Alexander D. Macrae: Just as an aside, haemophiliac A acid, although it's partnered with Pfizer, will bring a significant return to Sangamo, more than many people's wholly owned, ultra-rare disease has the advantage of partnering on a common disease like haemophilia. Of course, there are many people interested in a FABRIC program, so we're at this moment committed to driving it forward, to And as an aside as well as in our partnership, we are very pleased with the partnerships we have with Pfizer, Sanofi, Gilead, and now with Takeda. In the coming year, we will hand off the product to Pfizer, then hopefully, to Sanofi. And we are always open to new partners for people that share our love for science and the drive to make it into medicines for patients.

In the coming year, we will handle the product to falling Sir.

Hopefully the product to Sanofi and we are we are always will continue partners from people. This year are.

But the signs and the drive to make these into medicines for patients.

That's helpful. Thanks for taking the questions.

Thank you Sir.

Again, ladies and gentlemen, just as a reminder to secure for a phone question. You May Press Star then one on your Touchtone phone.

Our next question comes from the line of Jim Birchenough with Wells Fargo Securities. Please go ahead. Your line is now open.

Eric Joseph: That's helpful. Thanks for taking the questions.

Hi, Thanks for taking the questions. A this is a yacht ends you dialing in for Jim. So firstly just wanted.

Jan Virchinoff: Thank you, sir. And again, ladies and gentlemen, just as a reminder to queue up for a phone question, you may press star then 1 on your touchtone phone. Our next question comes from the line of Jan Virchinoff with Wells Fargo Security. Please go ahead; your line is now open. Hi, thanks for taking the questions. This is Yanan Zhu dialing in for Jim.

Did you ask about.

Hi to ask about the next generation in vivo gene editing program, you mentioned I think that you already manufactured as U.S. and 2.2.

So the question is have you finalized all the improvements that you're going to put into the next generation program.

Into the F.N. 2.2, and if that's a finalized then oh, so I wasn't I'm interested in how long and I N D, enabling study might take.

Yanan Zhu: So firstly, just wanted to ask about the next generation in vivo gene editing program. You mentioned, I think, that you already manufactured ZFN 2.2. So the question is, have you finalized all the improvements that you're going to put into the next generation program into ZFN 2.2? And if that's finalized, then also I'm interested in how long an IND-enabling study might take. Thanks.

Thanks.

So thank you for your question.

I realize I've, sometimes like people confuse of second generation, though.

Oh, the CFA now say its a new generation thing thinkers sums up let me see if I can see so.

The work that describes in the paper you spoke about it is a huge it generation of zinc fingers, where the zinc fingers themselves, we have enhanced the or binding capability and also reduce their off target.

Alexander D. Macrae: So thank you for your question, and I realize I've sometimes left people confused about the second generation of the CFN assets and the new generation of SingFingers themselves. Let me see if I can tease that out.

Alexander D. Macrae: The work that Ed describes in the paper that he spoke about is the new generation of zinc fingers, where the zinc fingers themselves have enhanced their binding capability and also reduced their off-target. And all that technology is described in a couple of papers that have been published in the past six months. The second generation of the ZFNs is appropriate for the albumin locus IV PRP, uses new technology, but more importantly, they alter the five prime and the three Prime of the cassette that deals with the transcription and the transduction of that set of zinc fingers. And our original plan had been to go into patients simply with that as the change from the previous IV PRP studies. And we had manufactured them, and they were ready to go.

And not all duct technologies as it is described in a couple of papers published in the past six months.

The second generation of the two.

See offense are appropriate for the.

Oh human book, because I view PRP.

Use the new technology, but more importantly, the altered the five prime and prime of the concept that deals with the transcription and the transduction of the sentencing fingers.

An original plan had been to go into patients simply with.

The change from the previews.

You studies.

We had manufacture them and they were ready to go.

As we learn more from the hemophilia a study.

Alexander D. Macrae: As we learned more from the Haemophilia A study, we realized that the problem was most likely to be in delivery, not in editing. When we use our technology to edit a mouse, monkey, or human cell, the editing is very reliable. And so our belief is that the results we saw earlier this year, where there was some editing but insufficient to provide enzyme for the patient, were as a result of not having enough of the AV transducing the cell. And the data points are both the Haemophilia A study and also the effect we saw in one patient, patient six in the study itself. So we're looking at ways that we can increase the amount of AAVs that we give, either by simply increasing the dose or by increasing the effectiveness of the AAVs, and we haven't spoken about how we've done that, but we will in due course, or about changing the ratio of the various AAVs that are part of this cocktail.

We realize that the problem was most likely to be in delivery and agency.

When we use our technology to exits in most of your human cells exiting is very reliable.

And so our belief is that the results. We saw earlier this year, where it was as some editing but insufficient for fight enzyme for the patient was as a result of not having enough of the sale of the a fee.

Trends juicing this the sale.

And the the data points are both the hemophilia a study where it suddenly becomes very effect from Q1 and three key.

Be 13 and also the the effect we saw in one patient and patient six studies so.

So we're looking at ways that we can increase the amount of zinc.

A fee that we give.

The third by simply increasing the doors.

Or by increasing the effectiveness of the Beacon, we haven't spoken about it we've done but we will in due course.

Or about changing the ratio of the of the various a feast or part of this call too.

What we want you to think about is although each one only improves the effectiveness by a few formed when you multiply together these or different improvements it becomes much more significant.

Alexander D. Macrae: And what we want you to think about is, although each one only improves the effectiveness by a few fold, when you multiply together these four different improvements, it becomes much more significant, and we feel it gives us confidence and gives the patients confidence more importantly that this truly will make a difference. So we have, if we use, if we use the new, sorry just to be absolutely explicit, using the new improved AV6 that we will talk about at a later date will involve some manufacturing and therefore drives the timeline for this project.

And we feel gives us confidence.

And gives us.

Gifts of patients confidence more more importantly, this truly will make a difference.

So we have great. If we use if we use the new sorry, just to upsell explicit.

Using the new and improved JV, six and we will talk about separately to date.

Some manufacturing and therefore drawings and timeline for this project.

Yanan Zhu: Yes. So to meet the goal of going into a clinic by year end 2020, is there a time when you need to nominate the candidate for that next generation program?

Yes.

So.

Good goal going into clinic by the year by year end 2020 .

If there are times that hill to nominate.

The candidate.

For that.

Next generation program.

Alexander D. Macrae: I would reassure you that Adrian and his team are... Looking at that timeline all the time, and we would have, we feel we can meet that. There are always things that can go wrong in science. But we, too, to, to suggest that we can get there suggests that we are, we believe that is doable with the manufacturing schedule that we use.

I would I would reassure you that between this team.

Our.

Looking at that time, all the time and we would have we feel we can beat it.

There's always things a couple comments sites, but we.

To to for Us to say that we think we can get there suggest that we are we believe that this dude, who was the manufacturing schedule that we use.

Yanan Zhu: Got it, got it. And then I just want to ask a couple of questions about the CAR T-REC program. Looking at the diagram on slide 32, it makes me think this might be an autologous candidate because the TCR was shown as intact on the cell. You didn't knock it out.

Got it got it and then just want here.

Ask a couple of questions on that.

Car T RAC program.

And looking at the diagram on slide 32.

It makes me think this might be an autologous.

Candidate.

Candidate because the Tcl T.R.

Was shown as.

Impact on the sell it didnt knock it out.

Adrienne Wilson: So, can you confirm this is an autologous T-cell product? Yeah, that's awesome. I've got it. Yeah, thanks for confirming that.

So can you confirm this is.

And our autologous.

T cell product.

Yes and also.

Got it.

Yep.

Thanks for confirming that and also.

Adrienne Wilson: And also, in terms of the Treg lineage, how do you achieve making the cell truly Treg? Is it transgenic expression of FOXP3? And also, is there a risk of doing damage to the transplant in case some of the cells are not truly Tregs but rather T effector cells?

In terms of the T rack lineage.

How do you.

Achieve.

The makena sell truly key Rad it transgenic transgenic expression of Fox P. Three.

And also.

Is there a risk.

Doing damage to the transplant in case some of the sales.

Are not truly hereafter, but rather.

Adrienne Wilson: Yes, thanks for that question. I'm going to be quite circumspect in how I answer because we've not disclosed a lot of the things you're asking, but I'll just simply say that yes, you're very astute in noticing that this is definitely an autologous therapy.

Factory Keith after itself. Thanks.

Yes.

I'm going to be quite circumspect, and how he also because weve not disclosed from.

All of the things you're off the ball to simply say that yes, youre your varies Jason or do you think that this is definitely an autologous therapy.

Adrienne Wilson: These are natural CAR Tregs which we transduced. I'm not sure if we've disclosed how we transduced them. Yeah, I don't think we've disclosed that, so I won't say that, but how we do it. But they're natural Tregs, which we... Purify from the patient and transduce. We are basically looking at renal transplant and HLA-A2 mismatch and that's probably as much as I'll say at this point, but you're absolutely right, this is an autologous play at the moment.

These are not true car T regs, which we transfer piece.

As we disclosed how we try to seize on.

Yeah, I think we've disclosed that so I wouldn't say that flow directly. They then natural T regs, which we.

Purified from the patients on Troms Jamie.

And.

We are basically looking at renal transplant on eight traits who mismatch.

Probably as much as I'll say at this point, but you're absolutely right.

Adrienne Wilson: Your question is fair, and one that we've thought of carefully and taken advice on because a renal transplant is a precious thing, and we don't want to do anything that puts the patient's safety or the longevity of the transplant at risk, so we're working very closely with some really smart renal centers to make sure that we do this carefully and well.

Look at the two of the Transcon service. So we're working very closely with some really.

Smart renal centers to make sure that we do this carefully and well, yes, we're really.

Adrienne Wilson: Yeah, and we're really, I'm pleased you brought this program up, you know, because we don't talk about it too much because I don't think folks are really still that aware of what we're doing. But yeah, we're really excited about this. You know, we see this as potentially being a really groundbreaking platform. We're the first people to be putting Tregs into humans, so we're ahead of the pack, and we're leveraging all the experience that we've gained over the years in both our HIV editing and other projects that we're doing, obviously. And, you know, we're really confident that we can do something radically important. And this is a really good place to test the hypothesis of the CAR Tregs as therapeutic agents and look at the safety and also the localization of those cells into the graft and look at a number of different biomarkers and potentially to see if we can reduce the immune suppression of the patients kept with steroids and MMS and tacrolinas. So, this is going to be a very exciting study, and it's a kind of a case of "watch this space," you know; this is going to be unfolding as a narrative next year.

These people this program as we talk about a few months because I don't think folks are really still not aware of what we're doing but we're really excited by this.

We see this as potentially being.

Really groundbreaking hands on with the fast peoples to be putting ttrrx into humans. So Rick.

The pack and leveraging.

The experience that we gain income.

The years in both our HIV added thing, but also.

From other projects that returning office.

Hi, Andy.

We are really confident that we can see something important.

This is a really good place to test the hypothesis all the car T regs therapeutic agents and look at the safety.

And also the localization of Berry sells into the growth and to look at a number of different biomarkers and potentially.

Simply can overages.

The immune suppression of patients kept with steroid MMS on Tacrolimus. So this is going to be a very exciting study and its a kind of a case. So watch this space is going to be unfolding as America's next year.

Yes, thanks for all the color, yes, Cartier AD is certainly very exciting area and congratulations on all the progress. Thanks for taking my question. Thank you and then you will note remember that slants actually published a review on court T. Rex actually stating is the next frontier for engineered cell therapies, and we see ourselves as really pioneering nurse bill.

Yanan Zhu: Yeah, thanks for all the color. Yeah, Khartoû Abbey is certainly a very exciting area, and congratulations on all the progress. Thanks for taking the time.

Adrienne Wilson: Thank you. And you'll remember that Science actually published a review on CAR Tregs, actually stating it as the next frontier for engineered cellular therapy. And we see ourselves as really pioneering this field.

Alexander D. Macrae: Thank you, sir. And with that, this concludes our time for questions, and I'd like to turn the program back over to Danny Macrae for any additional or closing remarks.

Thank you, Sir and with that this concludes our time for questions I would like to turn the program back over and in the gray for any additional or closing remarks.

Alexander D. Macrae: Thank you again to everyone for joining the call and for your questions today. We're pleased with the progress we've made in our clinical and preclinical programs and look forward to keeping you updated on future developments.

Thank you again to everyone for joining the call and for your questions today.

We are pleased with the progress is made in our clinical and preclinical programs and look forward to keeping you updated on future developments.

Great.

Operator: Have a great day. Thank you, presenters, and thank you to all of our attendees for joining us today. This concludes today's call. You may now disconnect, and have a wonderful day.

Thank you presenters and thank you to all of our attendees for joining US today. This concludes today's call. You may now disconnect and have a wonderful day.

Operator: BF-WATCH TV 2021