McDavid Stilwel - VP of Corporate Communications and IR Sandy Macrae - President and CEO Curt Herberts - SVP and CBO Edward Conner - SVP and CMO Michael Holmes - VP, Research Kathy Yi - SVP and CFO.

Whitney Ijem - JPMorgan Charles Duncan - Piper Jaffray Ritu Baral - Cowen & Company James Birchenough - Wells Fargo Securities.

Good afternoon and welcome to the Sangamo Therapeutics Conference Call. This call is being recorded. I will now pass you over to the coordinator of this event, McDavid Stilwel, Vice President of Corporate Communications and Investor Relations..

Good afternoon and thank you for joining Sangamo's management team on our conference call to discuss the company's first quarter 2017 financial results and also this afternoon’s announced collaboration with Pfizer.

As we begin, I’d like to point out that we’ll be referring to a slide presentation this afternoon, you may find a link to the slide presentation on our website, sangamo.com, on the Events and Presentations page of the Investors and Media section of the site.

The presentation is actually to be found on the webpage that is specific to this conference call event. I'd also like to remind everyone that the projections and forward-looking statements that we discuss during this conference call are based upon the information that we currently have available. This information will likely change over time.

By discussing our current perception of the market and the future performance of Sangamo with you today, we’re not undertaking an obligation to provide updates in the future. Actual results may differ substantially from what we discuss today and no one should assume at a later date that our comments from today are still valid.

We alert you to be aware of risks that are detailed in documents that the company files with the Securities and Exchange Commission, specifically our annual report on Form 10-K and on our quarterly reports on Form 10-Q.

These documents include important factors that could cause the actual results of the company's operations to differ materially from those contained in our projections or forward-looking statements.

With me today on this call are several members of Sangamo’s senior management, including Sandy Macrae, Chief Executive Officer; Kathy Yi, Chief Financial Officer; Ed Conner, Chief Medical Officer; Michael Holmes, Vice President of Research; and Curt Herberts, Chief Business Officer.

And again, we will refer to a slide presentation during this call and those slides are to be found on the Events and Presentations page of the Investors and Media section of our website on a webpage specific to this conference call event, And now, I'd like to turn the call over to Sandy..

Thank you, McDavid. I want to thank everyone for joining us this afternoon for our call. Our strategy is to build Sangamo Therapeutics overtime. In fact, company has ability to bring assets forward out of our research pipeline through clinical development to registration and commercialization. Some of these products we want to commercialize ourselves.

In other cases, we will determine the most appropriate means is to move them forward with a partner who has the right skills, focus, and resources to advance an individual program.

As shown on slide five, at the beginning of 2017, we laid out four key priorities for Sangamo, steps to take this year towards building the Sangamo Therapeutics of the future.

One, executing on the four clinical trials of our lead programs; two, extending our technical lead in genome editing where we have the most advanced, flexible and specific technology available; three, investing in R&D of alternative modes of delivery which will expand the potential use of genomic therapies; and fourth, finally, engaging with partners to help move these opportunities forward, not only existing partners such as Bioverativ for beta-thalassemia and sickle cell disease programs and Shire, our partner for Huntington's disease, but also to find partners who can effectively collaborate with us on other promising programs.

Therefore, turning to slide six, we're very excited to announce our partnership with Pfizer for the global development and commercialization of SB-525, our gene therapy for hemophilia A.

In a few moments, Curt Herberts will provide details of the terms of the collaboration, but first, I'd like to say a few words about what this partnership means for us at Sangamo.

While this transaction substantially strengthens our balance sheet, it also puts this very attractive gene therapy program into the hands of a partner with a strong hemophilia business and end-to-end manufacturing, technical and commercial capabilities in gene therapy.

Gene therapy is an important new product category for patients with hemophilia and one that promises with a single administration to free these patients from the lifelong dependence on factor infusions.

We believe our partnership with Pfizer will help make SB-525 a more successful product through thoughtful global development and commercialization at a scale that would not be possible for a company our size.

The market for hemophilia treatment is very competitive and Pfizer has the expertise, the commitment and the values and resources to make SB-525 a globally important product in this market. The collaboration also validates important research happening at Sangamo. We're rightly known for leading research into genome editing.

But over time, we have developed an expertise more generally across a range of genomic therapies, which include gene therapy, genome editing, gene regulation, and cell therapy. This allows us to make more pragmatic choices as we pair molecular engineering biology and technology with disease area.

For example, with SB-318 and 913, our progress for MPS I and MPS II, we're using genome editing, which we believe will provide lifelong benefit and of the most impact, altering the course of disease in young children before the tissue damage is made irreversible.

SB-525 for hemophilia A demonstrates our ability to work in gene therapy where we have used an iterative process to optimize the codon, the promoter, and the transgene cassette to create a product candidate that in pre-clinical non-human primate studies appears very competitive compared to other gene therapies being developed for this indication.

In coming years, as we continue to invest and perfect our genome editing technology, we will apply the knowledge gained into our other technology platforms in order to develop the right type of genomic therapy with the most benefit for the patients that we're here to serve.

Turning to slide seven, you will see us advance additional episomal gene therapy program such as our cDNA gene therapy for Fabry disease, which we are now pulling forward for IND in 2018. Likewise, our expertise in gene regulation using Zinc Finger Protein Transcription Factor Technology will continue to expand.

As you know we already have a partnership with this for Shire for Huntington's using this approach. Later in this call, Michael Holmes will shortly provide details of the latest research from our gene regulation program and the total-lowering approach, which may have applications in Alzheimer's and other tauopathies.

The enhancements to our Zinc Finger Nuclease Technology will extend our expertise in cell therapy as well, partly stemming from our legacy research program in HIV.

And while HIV is no longer a strategic focus of the company, the technology, experience, and safety data we've acquired has informed and enabled other cell therapy programs that are moving towards the clinic such as our BCL11A autologous therapies for beta-thalassemia and sickle disease, which we have partnered with Bioverativ, and our very interesting allogeneic T-cell oncology research.

Finally, this hemophilia partnership with Pfizer is an example of the type of partnership that can help Sangamo become a more valuable company and deliver on our mission by putting our assets into the hands of the right partners who have the capital, the resources, the expertise and the strategic focus to properly develop a commercially viable medicine that will transform the lives of patients.

You will see us advance other programs and partnerships when we believe the focus in franchise, either resources of a collaborator present the right fit and strategic alignment. I'll now turn the call to the team. After Curt provides an overview of the collaboration, Ed Conner will provide an update on our lead clinical programs.

Michael Holmes will provide an overview of some of the fantastic science being presented this week at the American Society for cell -- for Gene & Cell Therapy Annual Meeting here in Washington; and Kathy Yi will provide the financial results of the quarter. We'll then take your questions.

Curt?.

Thank you, Sandy. I'm excited to describe the overall deal structure but would first like to say a few words about the events that led to today's announcement. This is a highly competitive process, with multiple parties expressing strong interest in global rights to SB-525.

Pfizer stood out because they were able to demonstrate a deep understanding of gene therapy and the nuances of delivering and manufacturing. They also have a very strong hemophilia franchise and well-established relationships with the hemophilia patient communities in the United States, Europe, and rest of world.

As you know, during the course of diligence, parties interact across most functional areas, and we've been very impressed with their approach their teams have brought to these meetings and negotiations.

The structure of this collaboration creates significant synergies between our two companies to move 525 through development towards ELA and most importantly, commercialization.

We are enthusiastic to be working closely alongside Pfizer to develop SB-525 and potential follow-on gene therapy products for the benefit of hemophilia patients and their families. Turning to slide nine, under the terms of our collaboration agreement, Sangamo will receive a $70 million upfront payment from Pfizer.

We will be responsible for conducting Phase 1/2 clinical trials and will cover the cost of those studies up to a certain cap.

We are also responsible for process development and the first stage of manufacture and scale-up, and Pfizer will be financially and operationally responsible for subsequent development, manufacturing, and for commercialization around the world.

Sangamo is eligible to receive development, regulatory and first commercial sale milestone payments of up to $475 million, including up to $300 million for the development and commercialization of SB-525 specifically, and up to $175 million for follow-on hemophilia A gene therapy product candidates that may be developed under the collaboration.

Sangamo will also receive double-digit tiered royalties. Additionally, Sangamo will be collaborating with Pfizer on manufacturing and technical operations, utilizing viral delivery vectors. We are extremely excited by this deal and we look forward to working closely with our friends at Pfizer to make the collaboration and the product a success.

I'll now turn the call over to Ed Conner.

Ed?.

Thank you, Curt and hello everyone. It's very exciting teams here for our development group as we now have sites active across three of our gene editing programs in hemophilia B, MPS I and MPS II, and we're on track to activate sites for our gene therapy program in hemophilia A in the second quarter.

We want to conduct all of these four studies as rigorously as possible to ensure high-quality data as we gather initial information on safety and efficacy to best inform future registration of programs. I'll briefly now go through updates on a program-by-program basis. Let me start with SB-525 for severe hemophilia A on slide 13.

We're very excited to be collaborating with Pfizer on this program. Hemophilia is a global disease and our global expertise in clinical development will help us reach as many patients as possible. This program recently received orphan drug designation from the FDA and we're making strong progress on site engagement.

We have received IBC and RAC clearance and are engaged with four lead sites for initial activation and patient enrollment. We anticipate including up to 15 centers nationally to ensure an on-time enrollment for this Phase 1/2 study.

This reflects enthusiasm on the part of patients and providers for what we regard as a potential best-in-class gene therapy to treat severe hemophilia A. We will soon have first site activation for this study and continue to expect data possibly as soon as late this year, most likely early next year.

Shifting now to the genome editing programs, starting on slide 15, SB-FIX, our in vivo genome editing product for hemophilia B has the potential to provide stable factor production for the lifetime of the patient. This program has received orphan drug designation from the FDA and recently received fast track designation.

Four sites are now open and screening patients. As we expected, enrollment for this study presents special challenges. The hemophilia B patient population is very small, much smaller than hemophilia A, and we are also competing for patients with gene therapy clinical trials in more advanced phases of study.

We are adding at least three new clinical sites in the next few months in order to aid enrollment. Although we continue to anticipate data from the study in our earlier-projected timeframe, we will need to assess -- we will need to reassess this expectation if enrollment doesn't pick up soon.

We do not, however, expect similar challenges enrolling the MPS I and MPS II studies, both of which have opened for screening of the last few weeks. There is intense interest in these two studies among patients and their caregivers and also providers, and there is really no competitor program for our two in vivo genome editing approaches.

SB-318 and SB-913, our treatments for MPS I and MPS II, can potentially serve as lifelong cures if we are able to treat patients early enough in the course of their disease.

To be prudent, our trials must start in adults as we begin to evaluate the safety of these two treatments, but we recognize that the greatest potential benefit is in the treatment of children.

Turning to slide 16, both SB-318 and 913 have received special regulatory designations from the FDA, including orphan drug designation and pediatric rare disease designation, which can include a valuable tradable voucher for approvals. INDs are open and sites are now active and open for enrollment for both Phase 1/2 studies.

Furthermore, we will be activating multiple additional sites for both programs over the next few months for a total of eight sites for MPS I and seven sites for MPS II, and we expect steady enrollment enabling us to advance these studies on schedule.

In all our studies, we'll enroll a first cohort using the lowest dose we believe has therapeutic potential, conduct a safety review after a period of time has passed and then advance to a higher dose cohort. For the MPS programs, we continue to expect data possibly as soon as late this year, but most likely early next year.

We look forward to keeping investors up-to-date as we enroll these studies. All four trials are open label, but we will not release data until we have clinically relevant results. I want to touch briefly on our metrics for success across all our program as it's a frequent question that I receive.

First, safety is paramount in these first-in-human clinical trials as it is in all first-in-human trials, and we will monitor and evaluate this closely. Second, we will measures serum biomarkers to determine that the gene product is being produced at clinically relevant levels.

In the case of hemophilia programs, these are Factor VIII and Factor IX clotting protein activity levels. In the case of MPS I and II, we're measuring IDUA and IDS enzymes, respectively.

Factor activity levels are well correlated with clinical outcomes so the expectation is that reduction in bleeding events as well as decreased use of factor replacement would be observed with sufficient levels.

For MPS I and II, I want to emphasize that in patients on enzyme replacement therapy, current standard of care, serum levels of IDUA and IDS return to very low level just prior to their next ERT infusion, given the short half-life of the ERT.

This then gives us an opportunity early on to demonstrate that these key enzymes are being produced by our genomic therapies.

As we are studying adults who have lived with the effects of the disease for years, demonstration of clinical benefit in these initial MPS studies may be challenging, but the valuation of serum biomarkers will give a clear signal regarding pursuit of registrational studies and the movement into trials evaluating these treatments in children.

I'm very pleased with the progress we've made over the past five months. We will continue to work carefully and diligently to accomplish our goal through the reliable execution of the many small steps involved in successful clinical development.

And I want to close by saying how excited I am to be involved in the first-ever in vivo genome editing clinical trials. This technology has such enormous promise for the treatment of serious genetic diseases. This moment has been years coming as Zinc Finger Nucleases and other promising technologies have been developed.

I'll now turn the call to Michael Holmes, VP of Research.

Mike?.

Thanks Ed. Good afternoon everyone. We're actually dialing in from Washington, D.C. where Sangamo has a very significant presence this year at the 20th Annual Meeting of the American Society of Gene & Cell Therapy, or ASGCT.

Our team and collaborators have 10 oral presentations and nine posters at this year's meeting, with the presented data highlighting the breadth of our clinical and early-stage pipeline across genome editing, gene therapy, gene regulation, and cell therapy.

Although the conference is just getting started, I'm pleased to speak to the new and exciting data that we've already presented.

Earlier today, Ed Rebar, our Vice President of Technology, presented advancements in Zinc Finger Nuclease architecture that have enabled a reduction of off-target cleavage to below the level of detection by currently available assays.

As shown on slide 18, removal of the conserved phosphate context found in the beta sheet of the Zinc Finger Proteins greatly reduces off-target cleavage without sacrificing on-target cutting efficiency.

In his talk, Ed explained that these evolutionarily conserved regions of the Zinc Finger Protein are nonspecific points of contact with the genomic DNA that result in increased cleavage activity at the exposure of targeting specificity.

In other words, the positive charge on the phosphate contact interacts nonspecifically with the negative charge of the DNA backbone, which can result in increased binding to off-target locations in the genome.

By removing these phosphate contacts, Ed and his team had greatly reduced off-target cleavage while maintaining very high levels of on-target cutting.

And on slide 19, further gains in specificity were achieved in engineered mutations to the FokI cleavage domain that is fused to our design Zinc Finger Proteins to also remove non-specific contacts between the nuclease and the DNA.

On slide 20, you can see the off-target cleavage analysis of these new optimized ZFNs compared to the initial design ZFNs, where the removal of the ZFP phosphate DNA contacts results in undetectable off-target activity while maintaining greater than 80% on-target cutting activity.

Most importantly, as shown on slide 21, we were able to apply these combined improvements in the ZFN technology to achieve high levels of on-target cutting efficiency with undetectable levels of off-target cleavage at clinical scale in clinically relevant cell types. Moving on now, our scientist, Dr.

Bryan Zeitler, presented his team's CNS research from our gene regulation platform worked in conjunction with Dr. Brad Hyman, Director of the Alzheimer's Disease Research Center at Mass General and his team.

This collaboration examines a onetime gene regulation treatment using Zinc Finger Protein Transcription Factor Technology to lower tau mRNA and protein expression.

As the literature shows, the reduction of tau expression has shown to help reduce neuro fibrillary tangles in the brain and provide neuronal protection and reversal pathology in Alzheimer's and other tauopathy disease models.

As shown on slide 22, the presentation included data from in vivo studies in wild type mice that demonstrated we could achieve significant reduction of tau mRNA and protein in the mouse hippocampus, as well as sustain and well-tolerated Zinc Finger Protein Transcription Factor or ZFP-TF expression with minimal impact on inflammatory markers.

In addition, data shown on slide 23 from in vivo studies in an amyloid mouse model with Alzheimer's disease suggests that the single administration of ZFP-TF significantly reduced neurotic dystrophies in mice with established disease pathology. This the first time that a tau-lowering agent has demonstrated a reduction in neuronal dystrophies.

Turning to slide 24, the presentation also included specificity in off-target analysis in ZFP-TF-treated primary neurons, which revealed that tau was the only gene suppressed out of more than 26,000 coding transcripts analyzed.

Finally, new data in Bryan's presentation showed that effect of ZFP-TF treatment in lowering tau was durable up till the last measurement at 11 months. We are very pleased to be working with Dr.

Hyman, a leading investigator in Alzheimer's disease and tauopathy research, and we're very encouraged with his powerful assessment of our gene regulation technology when we announced initial data from this program earlier this year at the Alzheimer's and Parkinson's Disease Congress. Dr.

Hyman said, of the many approaches to reduce tau expression that we studied, Zinc Finger Protein Gene Regulation Technology is especially promising for its exquisite specificity, its potent reduction of tau protein expression, and it's potential to provide a durable, long-lasting effect with only a single administration.

From this point forward, our goal is to find the appropriate commercial partner with the right expertise to further develop this program in the clinic and towards commercialization. Finally, Sangamo's lead scientist in rare diseases, Thomas Wechsler, presented data from our cDNA gene therapy research program for Fabry disease.

Fabry is an X-linked lysosomal storage disorder caused by mutations in the GLA gene that codes for the alpha-galactosidase A enzyme or alpha-Gal A.

This mutation results in the buildup of certain lipid molecule in the body cells, resulting in a range of symptoms and life-threatening competitions that affect multiple disease and organ systems in the body.

Similar to the hemophilia cDNA gene therapy, we have now licensed to Pfizer, this program uses AAV6 to package and deliver an alpha-Gal A transgene to the liver where it's expressed episomally with a liver-specific promoter. We used a knockout mouse model to evaluate our gene therapy approach in comparison to wild type mice.

Turning to slide 25, we measured alpha-Gal A in the plasma in various tissues out to 60 days. The data show we were able to achieve enzyme activity levels in the plasma up to 100-fold greater than wild type and 10 -- 100-fold greater than wild type in tissues, including the liver, kidney, and spleen.

On slide 26, you can see that the alpha-Gal A enzymes secreted from the liver led to a significant reduction in the levels of accumulated lipid molecule substrates, Gb3 and Lyso Gb3, in target tissues like kidney and heart.

Based on these results, we are advancing our Fabry cDNA gene therapy program with preclinical IND-enabling work expected to be completed early next year ahead of an IND filing in the second half of 2018. We're excited about this program as the next therapeutic candidate to emerge from our growing gene therapy platform.

Over the course of the next few days, we'll have many other exciting data presentations here at ASGCT, including data from our non-viral delivery technology, human stem cell and B-cell applications for our cell therapy platform, improved assay development, and the therapeutic application of our ZFN and GM editing technology for monogenic disease.

These data are a great example of the broad applicability of our four technology platforms and the work great work being conducted at Sangamo as a leader in genomic therapy research. With that, I'll turn the call over to our CFO, Kathy Yi, to review our financials.

Kathy?.

Thank you, Michael. Good afternoon everyone. We issued a press release earlier today that included financial results for the first quarter of 2017, which I will briefly summarize, as well as discuss strategic financial benefits of the Pfizer collaboration agreement.

Turning to slide 28, net loss for the first quarter of 2017 was $16.6 million or $0.23 per share compared to a net loss of $16.5 million or $0.23 per share for the same period of 2016. This reflected cash used in operations of $13.1 million for the current quarter.

Through the remainder of the year, we continue to expect cash used in operations to steadily increase. Our total operating expenses were $20.2 million in the current quarter, including non-cash stock-based compensation of $2.8 million. R&D expenses were $12.9 million in the first quarter of 2017 compared to $15.3 million for the same period in 2016.

The decrease in R&D expenses was primarily due to completion of our external manufacturing expenses for the five clinical studies in 2017. G&A expenses were $7.3 million for the first quarter of 2017 compared to $5.4 million for the same period in 2016. The increase in G&A expenses was primarily due to corporate expenses and CFO transition cost.

We ended the quarter with $132.7 million in cash, cash equivalents, and investments.

We intend to use the $70 million upfront payment from the Pfizer collaboration agreement to develop additional therapeutic programs like our cDNA gene therapy for Fabry disease; to expand gene regulation using Zinc Finger Protein Technology in our manufacturing capabilities; and finally, to increase regulatory commercial infrastructure and G&A expenses to support these activities.

Thank you, and I will now turn the call over to Sandy..

Thank you, Kathy. Before we open the call for questions, let me conclude by congratulating the Sangamo family on the tremendous progress we have made in the last six months. We have three clinical trials opened for enrollment, with a fourth soon to open.

Importantly, Ed Conner and his group are carefully lining up the next key clinical sites to ensure the likely [ph] enrollment of these studies. Data expected from most studies, all four studies, as soon as the end of this year or more likely at the beginning of 2018.

Sangamo research is now dedicated to the translation of our groundbreaking science into clinical development. The group is focused on supporting our lead programs and on directing early research to produce a pipeline of candidates to pull forward for IND.

With the remarkable achievements from our technology group optimizing design, speed, efficiency, precision, and specificity, Zinc Finger Nuclease Technology continues to outpace the genome editing field. Change was challenging and Sangamo Therapeutics has gone through much evolution over the last year.

Most of our senior management is new or new to their positions. The company is more focused on clinical translation. And we seek to be collaborative and to advance our science in the most appropriate hands. In some cases, on our own; in some cases, in partnership.

In summary, I'm very pleased with the progress of the company, which is now more focused and more productive.

We're looking forward to the rest of 2017 and the excitement of enrollment of the clinical trials of our four lead programs, including the first-ever in vivo genome editing studies, which will be an incredible moment for Sangamo and an important moment for science. Operator, we're now ready for questions. .

Thank you. [Operator Instructions] And our first question comes from the line of Whitney Ijem of JPMorgan. Your line is now open..

Hi guys, thanks for taking the question and congratulations on the all the progress. Very exciting to see.

I guess first question on hemophilia A, just in light of some of the potency data you've presented relative to the other AAV-based hemophilia A programs, can you either tell us the starting dose that you're planning to look at? Or just talk a little bit more about how you're thinking about dose and maybe how you might be differentiated there?.

Thank you. Thank you. It really is an exciting time.

Ed, do you want to talk about how we're going to deal with that?.

Yes, we're starting in the 11 range, which we feel is a dose that has therapeutic potential. And importantly, we're assessing, as I said, not only safety, but looking at real-time for the Factor VIII activity levels.

And we are, again, aware of the potency data and have built out a protocol that allows us to adapt and respond to these Factor VIII activity levels appropriately..

Got it. And then just on the MPS I and MPS II programs, and I think I've asked this before but I'll ask it again.

Can you just remind us what the FDA has said or wants to see in the adult patients before you're allowed to move into the pediatric setting?.

So, we haven't had that specific an instruction from the FDA. But I'm sure you would agree that it is important in MPS I and II to intervene as early as possible so as the consequences of the disease can be prevented.

We've had really reasonable conversations with the FDA up to now, and we would -- we look forward to going to them as soon as we have data, not just from the MPS I and II programs, but from the four programs that validate AAV6 as a vector and including the hemophilia B that looks at the genome editing program in total..

Great. I'll stop there and hop back in queue. Thanks and congrats again..

Thank you..

Thank you. And our next question comes from the line of Charles Duncan of Piper Jaffray. Your line is now open..

Thanks for taking the question. A question regarding -- or first of all, congratulations on the Pfizer collaboration. Nice piece of external validation and execution on your team's part.

Wondering if you can provide a little more color on how that was competitive, if you will? What -- I think you mentioned that it was a competitive process, can you provide more color on that? Thanks..

Thank you, Charles. I'm not sure we can. All I can say is when we presented the data at the Hemophilia Congress, we had a lot of incoming interest, and we went through a formal process in which there were several sitters. And several people put it, for us, were very reasonable proposals and the final decision was difficult.

I think the things that appealed us with Pfizer, to be honest, were really not just the money. It was that they had a common view with us for global development. That they had experience within the market.

And when we met their senior leadership, Michael [Indiscernible] and I have a very common view of how this should be developed and the relationship between science and medicine. So, it really was a very good fit, and we're delighted with the partnership..

Well, congrats on that. And the second question I had was as a follow-up to the last questioner.

On MPS I and II, I'm very excited about those programs, but I'm kind of wondering when do you anticipate being able to provide some clinical information? I think it was hinted by the end of this year, but what would you see is a real win for this year? And then by the end of 2018, where would you like to be with these programs?.

Ed?.

Yes, so I think a real win would be, first and again, in any first-in-human trial seeing that your product is demonstrating as safe. But to get to your question, it's really the biochemical analysis, and not just in terms of the IDUA and IDS enzyme levels, but also looking at urine GAG.

So, it's the combination of those biochemical markers that we'll be determine, are we producing the gene product and is it having activity in terms of reducing waste product. To your point about clinical outcomes, again, we're measuring all those, but I think it was alluded to earlier as well.

Our ultimate goal and where we see the most benefit being derived is in children because these patients have had the ravages of the disease for years.

Now, we may see changes in clinical outcomes but I think importantly for us in terms of making decisions about the next step is what we see in terms of those biochemical changes in terms of the enzyme level and also the urine GAG as well..

And then I think you also talked about not reporting data on a patient-by-patient basis and I really appreciate that, but do you anticipate being able to give some updates in terms of patients enrolled? And then with regard to clinically meaningful information, was that in terms of results or certain number of patients that you look to report out at a certain time?.

Charles, we promise to be as open as we can and to share the data as it comes in..

Okay, sounds great. Thanks for the added color. Congrats on the deal with Pfizer..

Thank you. And our next question comes from the line of Ritu Baral of Cowen & Company. Your line is now open..

Good afternoon guys. Thanks for taking the question. I have some questions on the structure of the Pfizer partnership and then some follow-ups on the MPS I. Can you tell us -- one thing you mentioned that was part of the Pfizer deal was the fact that Sangamo was responsible for first scale up.

Can you give us a little more clarity on what manufacturing Sangamo is responsible for as part of this deal? Is this the Phase 3 product? And also, is there -- does the partnership establish any sort of development committee? What's the breakup of the members of that committee by company?.

So, Curt, are you able to give some color there?.

I am. Hi Ritu..

Hi..

So, the deal structure obviously is extremely important to ensure that both parties are getting what they want out of the relationship. So for us, as Sandy said, partnering with Pfizer as a global pharmaceutical company that brings a tremendous wealth of experience in hemophilia as well as broad development and manufacturing was critical for us.

Manufacturing is extremely important in gene therapy and so it was a key component for both parties that we have good continuity in terms of the manufacturing approach. And so Sangamo will be continuing that in terms of the initial process development and initial scale up and then handing over to Pfizer.

I can't give you any more detail in terms of that. And in terms of the overall deal structure, yes, it's managed by joint steering committees as well as a variety of subcommittees, and we've actually developed some pretty creative liaison components that will allow for the parties to work very closely together and to ensure success for the program..

And that was one of the pieces that we liked about in the discussions with Pfizer was their encouragement that we did this as a joint development in the initial stages and that the creative ways that they allowed for the committee structure..

The committee structure, can you say if it's roughly 50-50?.

So, each party has a vote, so not sure how much more detail you want about that. It's an equal vote, originally starting off with a couple of people on each side, joint steering committee and then a variety of subcommittees. All of them have equal membership and then they have general decision-making rules..

And having sat on many steering committees and joint development committees, this is a very fair and sensible way that it's been structured..

Got it. And then moving to MPS I, you guys have mentioned serum GAG levels, urine GAG levels. Does the protocol in any way allow for CSF measurements of either GAG or enzyme? And also since you are in adult patients, you mentioned that functional outcomes will be measured.

Can you tell us what those functional measures are? And is there any point in measuring neurocognition in these patients at this age or is it really something for the kids?.

So, I'll address your last program first -- I mean, your last question first, sorry.

In terms of measuring neurocognitive testing, it is something that we are, of course, including in the protocol as to whether or not we'll see a change protocol, of course, a year, for example, I think that's relatively unlikely, which is why we are relying very much on biochemical measurements as I talked about before.

With that said, we're doing a whole host of functional clinical testing, joint range of motion, six-minute walk tests, for example. I'm not going to go through the exhaustive list.

But also with regards to your testing for GAG, I guess, we do have the possibility of testing that within the cerebral spinal fluid and we will be mindful in terms of all the biological samples that we're collecting to make sure that we're appropriately evaluating the potential efficacy in both MPS I and II..

Great. Thanks for taking he questions guys..

[Operator Instructions] Our next question comes from the line of Jim Birchenough of Wells Fargo. Your line is now open..

Hi guys. I just wanted to congratulate you on all the progress and on the Pfizer deal specifically. Just stepping back on the gene editing platform specifically, we often hear about the specificity of Zinc Finger Nucleases, but the speed of use of CRISPR.

Could you maybe provide some context, Sandy, on how you see your gene editing platform standing up to things like CRISPR technology?.

Thanks. I'm delighted to, Jim.

Michael, would you like to talk with this?.

Sure. Certainly. I'd be happy to take this question.

I think Ed gave a great presentation today at ASGCT really just talking about the advancements in our ZFN architectures with regards to, not only the improved design density, but as well as the specificity, where truly we can achieve unprecedented levels of on-target activity with undetectable levels of off-target activity.

So, I think putting that in context as compared to the other technology platforms, I mean, what we're seeing in a sense is at -- in the clinically relevant cell lines at clinical scale, just levels of both on-target modification as well as specificity that we just -- you just don't see from the other platforms yet in terms of what's been presented in the various conferences.

And so I think when you look also in terms of some of the advantages of Zinc Finger Nucleases is that we have a deep understanding of how the ZFP actually interacts with the DNA and that we can actually go and essentially modify the contacts with DNA to also go back and further enhance on-target activity as well as increasing specificity that is not something that the other platforms can do.

So--.

But to your question, Jim, one of the things, I think, that is not well-known is we've now reached a point where for the majority of the targets within the genome, maybe 60%, we can provide Zinc Finger -- a good set of Zinc Fingers within 10 days.

And to us, that is a very good, reasonable time to target for something that really is a medicine in development. And if you want to cover the whole of the genome, we can easily do that. It might just take a little longer to make additional sets of fingers.

So, we're very pleased by the number of places we can target within the genome, the speed with which we can do it within 10 days, and as Mike said, with the on-target efficacy and the off-target specificity..

And then just on the Pfizer collaboration, is there, as part of the agreement, a formal opt-in by Pfizer after the Phase 1/2 data? Or how do we think about the next milestone in the collaboration?.

Curt?.

Hi, Jim. So, deal structure is extremely important. I want to be really clear this is not an option deal at all. So, this a full global development and commercialization licensing collaboration with Pfizer. So, the first milestones are focused on clinical and regulatory events. We have not broken those out.

So, the only detail we've given is on slide nine and then within the appropriate press release. But we're very excited about moving forward. And Sangamo will be responsible for running the Phase 1/2 clinical study, and Ed Conner and his team are doing a great job..

And then just may be finally on -- sorry, something earlier-stage on the tau program that was highlighted today at ASGCT, a lot of enthusiasm there. It seems like with direct intrahippocampal injection, you get something like 75% tau reduction. With intravenous, something less.

Can you maybe talk about how you think about the delivery of your technology here? And how far away are we from actually moving something towards the clinic? And do you think it will be a direct hippocampal injection or IV?.

Mike?.

So, I think from the presentation today, we showed that we can achieve greater than 90% down-regulation by direct injection into the hippocampus.

And then we showed some of our earlier-stage work that we can actually access a wider area of the CNS using the AAV that we've engineered, where we can achieve somewhere between 30% and 70% down-regulation of tau in different areas of the brain. So, we're very encouraged by this.

This is something that we'll take a very close look at in terms of what is the best delivery method for us to achieve the greatest coverage for down-regulating tau. I think it's a little bit early stage for us to talk about when we think we would be going to clinic.

But so far the sort of research studies that we've been in look extremely encouraging..

And Jim, this is one place it's about benefit-risk. So, if you are going for one of the very severe tauopathies, one of the frontotemporal dementias or PSP, you could imagine that the risk -- the benefit/risk of a direct brain injection is sensible, is reasonable.

And if in some day in the future we can ensure AAV delivery across the whole of the brain, intravenous would be the route of choice for more broad Alzheimer's treatment. But these are early days.

Again, this is another program where we've had a lot of interest since the presentation at the Alzheimer's Conference and lots of people are coming to look and help us think about this..

Great. Thanks for the questions..

Thank you. And our next question comes from a follow-up of the line Ritu Baral of Cowen and Company. Your line is now open..

Thanks for taking the follow-up guys. As we think about the Fabry program, two questions.

Any material differences in what the first Fabry clinical trial might be compared to the design of the MPSs that you shared? And also can you detail more specifics on exactly what's left before IND filing pre-clinically?.

So, why don't we do that in two parts? Ed, you want to take the clinical bit? And then, Mike, you take the IND piece..

Yes, sure. So, I think it would follow a similar strategy in terms of looking an alpha-Gal A levels and also looking at Gb3.

I think for Fabry, or Fabry, it's really, at the end of the day, about patient selection and so there are a variety of endpoints as you're likely aware, but I think a renal endpoint is a strong potential in terms of looking for a modifiable outcome over the course of the year in the Phase 1 study.

So there, you would be looking changes in creatinine clearance, for example, over time. And there is a possibility from a clinical design standpoint that you could observe those changes and that's been seen for other products that have been approved for Fabry..

So, you'd rather do like a longer study eliminating the need for biopsy?.

Yes. I mean, I -- it is a question. And again, it's based off of the clinical effect that you would observe both in terms of stabilization of creatinine clearance for GFR loss.

It may be that we would pursue a biopsy route, but I think given what's known about the correlation of the biochemical levels along with your changes in GFR, I'm not sure that that's particularly necessary now and it's clearly impactful to patients to do that..

Yes, and I'm sure you would imagine, there are very great similarities from this and Factor VIII as a gene therapy, we can measure biochemical changes and then look over the longer term on functional outcomes and histology..

That's right..

Mike, do you want to talk about how far -- about the process to IND?.

Yes, certainly. As Ed mentioned that this is an approach that's very similar to the Factor VIII approach as far as using AAV6 and using a gene therapy approach for Fabry. So, in a sense, the preclinical development plan would proceed the same way that we had proceeded with the hemophilia A program.

And therefore, in terms of the plan for moving forward with IND naming studies, we would expect to do some additional studies in some of the Fabry disease models that are in mice and other preclinical animal models as well as perform some of the IND-enabling safety studies very similar to what we did with hemophilia A..

But the good thing is this is a pathway we've done before..

Yes, absolutely. So, that's why as we mentioned in this script that we would expect to be completing these studies in the first half of 2018 with the expectation of filing the IND shortly thereafter in the second half of the year..

Got it. Thanks for taking the follow-ups everyone..

Our pleasure..

Thank you. And our next question comes from the line of Jim Birchenough of Wells Fargo. Your line is now open..

Yes hi guys. Just a follow-up on the in vivo gene editing. One of the questions we get is regarding capsid load. And I think intuitively, people think about two gene editing vectors and then the gene replacement and total viral load that reacts.

But when you think about the program, how do you think about capsid load and safety of your approach versus a straight gene therapy approach?.

So, yes, this is a question we often get asked, and safety is important. And from when we talk about viral load, we talk about the total viral load, which includes the one for each zinc finger and one for the payload. And the range of viral loads that we're in are similar to what other gene therapies are.

So, we're comfortable that the safety of this will be similar to what has been seen for gene therapy.

Does that answer your question, Jim?.

Yes. No, that's helpful. And maybe to the extent that delivery is important, Sandy, could you maybe describe what you're doing to advance next-generation delivery technologies, whether that's nanoparticles or next-generation capsid? Maybe if you could spend a moment on that..

Yes, I think we've done a remarkable job to push things forward into the INDs and to the clinic, and what we're doing is going back and understanding each of the steps in what I call the supply chain that takes you from the AAPs being injected into the patient, from them being taken up in the liver, from it being transcribed and translated and producing the protein out.

And what I want to do is I want to understand each part of that process so as we can work out how to improve each part of it and make the next version even better. We believe that this is a platform that we're going to be using for a long time.

We believe it has the ability to draw new payloads, and therefore, we want to optimize and tune it so it truly is the -- an answer for lots of diseases..

Great. Thanks for taking the follow-ups..

Thank you..

Thank you. And I'm showing no further questions at this time. I would now like to turn the call over to Dr. Sandy Macrae for closing remarks..

Thank you very much. And I want to thank everyone for joining us today. This has been a great day for Sangamo with the signing today of the deal with Pfizer and we're delighted to move forward with our new partners. And thank you all for your interest and your words of congratulation..

Ladies and gentlemen, thank you for participating in today's conference. This concludes today's program. You may all disconnect. Everyone have a great day..