McDavid Stilwel - VP of Corporate Communications and IR Sandy Macrae - President and CEO Edward Conner - CMO Michael Holmes - VP of Research Ward Wolff - EVP and CFO.

Gena Wang - Jefferies Whitney Ijem - JPMorgan Charles Duncan - Piper Jaffray Ritu Baral - Cowen & Company.

Good day, and welcome to the Sangamo Therapeutics teleconference to discuss the Fourth Quarter and Full Year 2016 Financial Results. This call is being recorded. I will now pass you over to your coordinator of this event, McDavid Stilwel, Vice President of Corporate Communications and Investor Relations..

Good morning and thank you for joining Sangamo's management team on our conference call to discuss the company's fourth quarter and full year 2016 financial results.

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

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 are 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 quarterly reports on Form 10-Q and on our annual report on Form 10-K.

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; Ward Wolff, our Retiring Chief Financial Officer; Ed Conner, Chief Medical Officer; Michael Holmes, Vice President of Research; and Curt Herberts, Chief Business Officer.

Also with us today, is Kathy Yi who joins Sangamo yesterday to become our new CFO upon Ward’s retirement. Following this introduction, Sandy will highlight recent changes and introduce the company’s areas of focus for 2017.

Ed Connor, will discuss our clinical development programs, Michael Holmes will provide details of the technology and research programs. Ward will than briefly review fourth quarter and full year financial results for 2016 as well as our financial guidance for 2017. Following Sandy’s closing remarks, we will open this call for questions.

Again, we will refer to a slide presentation during this call, those slides are to be found on the Events and Presentations page of the Investors and Media section of our website on a link specifically for this morning’s call on that page. And now, I'd like to turn the call over to Sandy..

Thank you, McDavid. I want to thank everyone for joining us this morning for our call. While the occasion for today’s call is to 2016 yearend review of business and financial results, I’ll also focus on the future.

2017 will be a historic year for genome editing and especially for Sangamo, as we conduct the first ever in vivo genome editing clinical trials. So first, I’ll start with some comments about few of our recent announcements. Sangamo involved at the start to this year to become Sangamo Therapeutics.

As you see on slide four, I want to take a message to explain this rebranding. As Sangamo we have a 20 year heritage of being at the cutting edge of genome editing and gene therapy and we celebrate that heritage.

We choose our therapeutics to the Sangamo name because we have evolved from a Biosciences research company to an organization that is focused on the clinical development of genomic therapies. Science at Sangamo Therapeutics is a means to develop new medicines with the potential transform the lives of patients living with serious genetic diseases.

We’ve rebranded the company, but underneath that lie some very important work underpinning the changes I brought in since joining the company. In the middle of last year, as you can see on slide five, we have hired new talents and filled critical positions.

I believe just yesterday we announced that Kathy Yi has joined Sangamo and will be our new CFO after Ward retires from the company in early March. Kathy joins us from Novartis, where she served as Head of Finance for the global inhalation technical research and development organizations in both California and this was headquarters.

She bring more than 20 years of experience spanning various disciplines in technology and finance. We have recently announced a new CMO, our newly appointed Chief Business Officer and a new Head of Technical Operations.

We now have appropriate clinical development department, we have the technology and the manufacturing capability to ensure the quality of our product. We also established a commercial planning department that work close and closely coordinate with our clinical development team on product planning.

With all of this, we are assembling the capabilities needed to pursue our vision of developing our products from the research labs at Sangamo to clinical development to commercialization.

Importantly, because science and innovation are the core of Sangamo, we have refreshed the discovery organization and we will be complimenting the scientific technologies with new biology expertise in the company.

Turning to slide six our focus for 2016, this year our top priority, our number one priority is to conduct four clinical trials for our lead programs, which include gene therapy and genome editing product candidates.

We will take Sangamo's zinc finger nucleus technology the most advanced flexible and precise genome editing technology available into patients for the first effort in vivo genome editing clinical trials. The development and continued evolution of our genome editing platform and zinc nucleus technology is another key focus for 2017.

Over the course of this year as we take ZFN into human clinical trials and as we present and published in our architectural improvements from the last few years, we believe you will understand the zinc finger nucleus has set the standard for advanced flexible and precise therapeutic genome editing technology.

So we believe we've now reached a state where it's not really molecular biology, but like engineering. We understand the science behind the interaction between zinc finger proteins and DNA and we are now also improving on our delivery technology, which will open the field of genome editing to many more applications.

And is a critical step to realize the full potential of this technology. Finally a company of our size cannot do this alone, we need to be thoughtful, pragmatic and a good partner with the various companies we work with and who are interested in working with us.

We were very pleased when Bioverativ announced that they were eager to take the human hemoglobinopathy assays of our Biogen collaboration into the pipeline of their newly formed independent company.

As you know Bioverativ is a blood disorder focused spin out from Biogen and we believe they will be a very strong partner for our work on beta thalassemia and sickle cell disease. Our collaboration is now engaged and lead to preclinical work. Turning to slide seven, first and foremost, 2017 is a big clinical trial delivery in our four lead programs.

I deliberately repeat this to emphasize that inherent what want to see from Sangamo that I know what is expected of us this year. So I'll now turn the call over to Ed Conner, our Chief Medical Officer to discuss these development programs.

Ed joined us at the end of November and has a strong history of success in clinical development for rare disease programs. He joins us from UltraGenics and earlier work to BioMarin and Genentech.

Ed?.

Thank you, Sandy and hello everyone. I'm very excited to be here at Sangamo to lead clinical development as we execute on the first ever in vivo genome editing clinical trials. In the two short months since I took leadership of the clinical team we've already grown significantly.

We now have the right people in place and the appropriate organizational structure to translate Sangamo's cutting edge research into clinical success.

We have a fully staffed clinical operations teams to efficiently manage our clinical development timelines and we hired two medical directors with experience in hemophilia and lysosomal storage disorders to ensure we properly address patient's unmet medical needs in the therapeutic development of these programs.

With these recent changes, I'm confident we will achieve timely and clinically meaningful results from our four lead programs in Hemophilia A, Hemophilia B, MPS I and MPS II. Let me start with SB-525 for hemophilia A. this program is the most recent to receive IND clearance from the FDA.

As you'll see on the mechanistic cartoon on slide nine it is traditional gene therapy where the transgene is packaged into an AAV vector. We use AAV 6 to specifically target uptake and deliver cells delivered via a single IV infusion. The transgene goes to the liver where the gene is expressed epidermally.

Despite the fact that there are factor replacement products approved for hemophilia A, as well as some long lasting type of products that are being developed, we believe a patients want to avoid bleeds [ph] and arthropathies that are the consequence of this disease as well as avoiding frequent infusions of replacement factor.

Our gene therapy SB-525 hold significant potential as a one-time treatment that will eliminate factors infusions and we believe what we have is the best-in-class, most spoken cDNA contract. Slide 10 compares non-human primate data for SB-525 with competitor data.

These are not head-to-head data, I want to stress, but at least in this comparison, the Sangamo construct appears more potent than Spark and BioMarin. We are looking forward to initiating the Phase 1/2 clinical trial. The IND is open and we expect to open the first site in the second quarter of this year.

You'll find the summary of the protocol on slide 11. We expect this study will be relatively easy to enroll as there are significant excitements among hemophilia key opinion leaders about this approach and this product in particular. We'll treat three patients in each cohort with safety reviews occurring before the study advances to the next cohort.

I want to shift now to the genome editing platform. Slide 12 shows a cartoon illustrating the approach for all three of the in vivo genome editing programs we're advancing in the human clinical trials this year.

Here we still use AAV6 as the delivery vehicle, but what we infuse in the patients is a mixture of the transgene and choosing finger nucleases. Again it is a single infusion into the patient, again it trans backs [ph] to the liver.

The zinc finger is recognized canonical sequences in the DNA in this case within an intran of the albumin gene, the [indiscernible] nucleus attached to the zinc fingers, cleaves the DNA with a double strand break and the transgene is dropped into that break.

The transgene at the bottom right of the slide has been expressed using the endogenous albumin promoter and this is one of the strongest promoters in the body. We believe that this then allows to transfer production of this gene's protein from the liver.

The idea is to create a one-time treatment and that the genome editing will ensure sustained protein productions throughout life. SB-F9, our in vivo genome editing product for hemophilia B has the potential to provide stable factor production through the life time of the patient.

The IND is open, sites were open and we are screening patients -- and we are screening patients. The protocols number is on slide13.

We will start with the lowest dose that we believe has therapeutic potential conduct a thoughtful and appropriate safety review in light of this being the first time this therapeutic approach has been introduced in the patients. Then proceed to a higher dose cohort over three cohorts.

Hemophilia B is more competitive space, the much smaller patient population than hemophilia A. We expect this trial will enroll more slowly than the other studies we are running, but still anticipate receiving data from the study around year-end 2017 or early 2018.

Moving on now to the other 2G net earning programs that we have, these are potential treatments for MPS I and MPS II and are summarized on slide 14. Here the medical need is even more obvious because if the patients aren’t treated early enough they develop a serious of [indiscernible] with damage to many organs in the body.

We're developing SB-318 and SB-913 the treatments for MPS I and MPS II and potentially a late lung cure if we're able to treat patients early enough in the course of their disease. To be prudent, we have to start with trials in adults, but we recognize that the greatest potential benefit is in the treatment of children.

INDs are open for these Phase 1/2 studies and sites will be open and will be screening patient this quarter. There is good awareness and interest among families and patients for these studies.

Like the hemophilia B study, we all enroll first cohort using the lowest dose, we believe has therapeutic potential conduct a safety review after a period of time is past and then advance to a higher dose cohort. Slide 15 summarizes the progress, we have made with all these studies so far. We're exactly on track with what we promise to deliver at J.P.

Morgan earlier this year. We have GMP large scale manufacturing competed for all of our clinical trials, we have orphan designation for two of them already, and another two of them are in process.

Yesterday, we announced that the MPS I program has received rare pediatric disease designation and we have all submitted an application for that designation for MPS II. We have the first site open for hemophilia B, we'll have sites open for MPS I and MPS II this quarter and for hemophilia A in the second quarter.

We look forward to keeping investors up-to-date as we enroll these studies. All four trials were open label, but we will not release data until we have clinically relevant results. We expect to report information from each of these studies along approximately the same timeline, late this year or early 2018.

As we're very pleased with the progress we've made over past two months, we will continue to work carefully and diligently to accomplish our goals for the reliable execution of the many small steps involved in successful clinical development.

I want to close by saying how excited I am to be involved in the first ever in vivo genome editing clinical trials. The technology has such enormous promise for the treatment of serious genetic divisions. This moment has been years coming as zinc finger nucleus is another promising technology that’s been developed.

In 2017, ZFN will advance into studies of somatic gene editing. I’ll now turn the call over to Michael Holmes, VP of Research.

Mike?.

Thanks, Ed, good morning. At Sangamo our early research programs are focused on improvements that make ZFN genome editing appropriate for human therapeutics. Today I want to talk to you about two programs where our advancements of the potential to bring the benefits of this technology to more patients.

So first is about improvements of the ZFN platform itself that have increased on-target efficiency and greatly reduce off-target cutting. On slide 17 what I have expanded here is a cartoon of a pair of zinc finger nucleases bound to DNA.

You should visualize zinc fingers as the protein factors that recognize and bind the DNA and attached is the Fok 1 nuclease that allows the cleavage to happen.

Zinc fingers are modular, comprised of five or six fingers and weave such a large and well characterized liberate fingers that we are now able to construct a set of zinc fingers to target any chosen location of the genome in a matter of days and achieve the cutting level of greater than 70% on the first pass.

Since we’re using ZFN to develop a new class of human therapeutics to help patients with genetic diseases it is critical for us to have the ability to refine and optimize ZFN performance in cells.

We’ve developed new linkers joining the finger modules in Fok 1 nuclease that allow us skip DNA basis and significantly improve our design density to target DNA. Turning to slide 18 and work that we presented last month at the Keystone Symposium on precision genome editing.

We’ve developed several approaches to maximize potency and specificity including abolishing non-specific phosphate contacts between the zinc finger and DNA and also ratio optimization of the two ZFNs being introduced in the cells.

And on slide 19 putting all these strategies together the linker, the abolition of phosphate contacts and the adjustments in the ZFN ratios we can now target virtually any basement genome with unmatched efficacy and specificity.

I want to emphasis that this slide 19 shows the results from one of our targets where we’ve used these recent improvements in the ZFN platform. Along the bottom are all the locations of the genome where these ZFNs could cut. The red part is the on target and it’s now at 80% although we’ve been able to achieve modification levels of greater than 80%.

The bars you can’t see in the graph, which represents the analysis of all the potential off target sites are now below the level of quantification. We can now move the off target editing below where it can be detected with current state of the art assays.

We’ve used unbiased oligo nuclear type capture assays as well as next generation sequencing to provide highly sensitive detection of off target cleavage. Since we are developing this technology for use in patients it is critical that we get it right. Off target cleavage is also focus of the FDA.

This rigorous detection method we use is the highest standard in the field as in contrast to recent data reported last year by some of the newer genome editing companies, which use a biased bioinformatics based approach.

Another point to highlight about these data are that this study was performed in the appropriate clinically relevant cell type at clinical scale. It’s one thing to do this in a petri dish at research scale, it's a very different thing and much hard to do under the conditions that mimic what we would do clinically.

These advancements and the rigor of our analysis help us bring our ZFN genome editing technology to more applications that can help patients. The slide depicts actual data where we’ve not got the [indiscernible] cancer. That’s an example of how we’re using this new technology to develop precise medicines.

Turning to slide 20, the second important topic I want to discuss today is LNP delivery. Lipid nanoparticles or LNP as you may know are small multi-component particles, which are taken up through the LVL receptor in the liver.

Some of the benefits of LNP delivery are that they are not a target of neutralize nanobodies and that LNP allow for repeat administration in order to dose to effect. These advancements in delivery will enable our technology to treat new genetically tractable disease and eventually help more patients.

Let me show you some data around these of LNPs who delivers ZFNs in mice. On slide 21, you’ll see data from the set of test ZFNs targeting the transthyretin or TTRG. On the left hand side you can see the level of editing where we’ve achieved 60% knock out editing within the liver with ZFNs administered via lipid nanoparticles.

The roughly other 40% of cells are blood cells in fibrous tissue, which do not express TTR and are not target for delivery by the LNPs. This is a maximum amount of editing that is reflected in the 90% protein knockdown on the right hand side. We’ve also done this with PCF-K9 [ph] amongst other genes.

We now believe, we have the ability of used in mice and we are moving it into non-human primates, to knockdown any gene within the liver with lipid nanoparticles.. On the next slide 22, we also believe we can use this approach to target the insertion of a therapeutic transgene being deliver.

Two things to take away from this side, the first is the target knocking of a gene we use the lipid nanopartciles to deliver the zinc figures and at the same time use AAV to deliver the transgene. The payload that we want to drop into the albumin locus.

In this specific example, we’re inserting the IDS gene there is normally mutated in MPS II patient into the albumin locus. That's the first dose, and on the second and third dose we repeat administer ZFNs with LNPs to drive additional editing and targeted insertion of IDS gene.

With LNP re-administration of additional ZFNs, we achieved additional levels of editing allowing for gradually increasing the amount of genetic payload integrated into the target site and increase the amounts of replacement enzymes produced from the liver.

This approach allows us to repeat dose and probably reach to desired therapeutic effect and as the potential to expand the number and types of genome editing applications we can pursue in the liver. We’re very excited by LNP and look forward to sharing nonhuman primate data later this year. With that, I’ll turn the call over to Ward our CFO.

Ward?.

Thank you, Michael and good morning everyone. As you’ll see on slide 24, for the fourth quarter of 2016 the company reported a consolidated net loss of $9.6 million or $0.14 per share compared to a net loss of $14 million or $0.20 per share for the fourth quarter of 2015.

The net loss for the full year 2016 was $71.7 million or $1.02 per share compared to a net loss of $40.7 million or $0.58 per share for 2015. We ended 2016 with approximately $140 million in cash, cash equivalents, short-term investments and interest receivable.

Revenues in the fourth quarter of 2016 were $8.9 million compared to $9.1 million for the same period in 2015. Fourth quarter 2016 revenues comprised revenue from Sangamo's collaboration agreements with Bioverativ, Shire, Dow AgroSciences and Sigma-Aldrich, enabling technology agreements and approximately $100,000 of revenue from research grants.

For research services performed under the collaboration agreements with Bioverativ and Shire we recognized $1.4 million and $100,000 of revenues during the quarter respectively. For the full year 2016, we are pleased to have exceeded our revenue guidance and met our guided ranges for operating expenses and year-end cash.

Revenues for the full year 2016 were $19.4 million compared to $39.5 million in 2015. With the decrease primarily due to the strategic amendment of our collaboration agreement with Shire, as well as decreases in revenues year-over-year related to our agreements with Sigma and Bioverativ.

Total operating expenses for the fourth quarter of 2015 were $18.8 million compared to $24.8 million for the same period in 2015. Research and development expenses were $13.9 million in the fourth quarter of 2016 compared to $19.9 million for the fourth quarter of 2015.

The decrease was primarily due to the completion of all our external manufacturing expenses and preparation for our clinical studies in 2017. General and administrative expenses were $4.9 million for both the fourth quarter of 2016 and 2015.

Non-cash stock-based compensation expense was $1.9 million for the quarter with $1.1 million in research and development and $800,000 in general and administrative. For the full year 2016 total operating expenses were $91.9 million compared to $86.4 million in 2015.

With the increase primarily attributed to the increased external clinical expenses as well as increased expenses relating to salaries and benefits, consulting services and other corporate cost.

Turning to the balance sheet, as I noted earlier, Sangamo ended the fourth quarter of 2016 with $143 million in cash, cash equivalent, short-term investments and interest receivable. Our net cash used in operating activities was $12.6 million for fourth quarter resulting in $66.5 million net cash used in operating activities for the full year 2016.

Regarding our financial guidance for 2017, on slide 25 we expect revenues for the year to be in the range of $14 million to $19 million, revenues include partial recognition of upfront payments sub-licensing revenues, reimbursement of research services and milestone payments from existing collaborations.

We expect to incur operating expenses in the range of $100 million to $110 million in 2017 including non-cash stock-based compensation expense. Of note, the company manufactured and released CGMP materials in 2016 for all currently planned clinical trials.

We anticipate ending 2017 with at least $60 million in cash and equivalents and this is inclusive of research funding from existing collaborators, but does not include funds arising from any new collaborations or partnerships or other sources of capital.

As you know Sangamo has historically been a prudent custodian of shareholder cash resources, we will continue to evaluate appropriate collaboration and partnership opportunities that have been hallmark of our non-dilutive financings and operating expense reimbursement.

In summary, the company is in solid financial position as we begin 2017 with the cash runway to fund the clinical studies of our four lead therapeutic programs in hemophilia and lysosomal storage disorders. We look forward to a pivotal year ahead as we advance these programs into the clinic. Thank you. I will now turn the call back over to Sandy. .

Thank you, Ward. I hope we've shown you today that Sangamo now has a balanced portfolio of clinical products, preclinical development and early research. And you can see that on slide 27.

We have the four lead product candidates that are going into the clinic with our new clinical development group will start to recruit patients very soon and we expect data at the end of this year or at the beginning of next.

We are also excited by our middle portfolio, which includes a hemoglobinopathies programs with Bioverativ and Huntington's with Shire. Our early research zinc finger nucleus architecture improvements and our hopes for delivery promise to yield exciting new programs in future years.

In short, we've accomplished everything we promised earlier this year and importantly we are on track to accomplish in 2017 the plans we laid out at the beginning of the year. We expect to maintain this momentum throughout the years. We've made great strides in recruiting front and have completed the replenishment of our senior leadership.

We've made significant progress in the clinical setting, our newly implemented systems and processes are working as planned and our science I believe is better than before. Before we move to your questions, I want to bring us back to the priorities and themes for 2017 slide 28.

I joined Sangamo because of the promise of the science here, which has exceeded my expectations. Zinc finger nucleus are the most flexible and precise genome editing technology. This year, we will finally advances genome editing platform into in vivo human clinical trials.

This will be a remarkable moment for Sangamo, but also for science in general as for the first time ever we will permanently insert a new gene into a patient's DNA. We look forward to keeping you updated on our progress and especially to sharing data with you late this year and in early 2018. Operator, we are now ready for questions. .

[Operator Instructions] Our first question comes from Gena Wang with Jefferies..

Thank you for taking my questions and congratulations on all the progress. So my first question is regarding the lipid nanoparticle.

Just wondering from your scientific point of view have you explore combining the zinc finger nucleus mRNA together with the donor sequence or all in lipid nanoparticle versus current approach that lipid nanoparticle delivered at the ZFN and the AAV delivered the donor sequence..

Thank you, Gena thank you for your question.

Mike do you want to talk to that?.

Certainly I think if I got your question correctly, we presented data in combing ZFN delivery using LNPs with AV delivery of the donor.

Your question I believe was around have we tried it where essentially the donor was also delivered via lipid nanoparticle? Is that the right question Gena?.

Yes. .

So that’s something that we're certainly looking at as a way of trying to further expand our use of lipid nanoparticles, this is a very challenging -- sort of challenging approach to try and get rights lipid nanoparticles have worked with messenger RNA, but they haven’t worked as well with the use of DNA delivery.

So that is something that we’re looking at, but that’s still at the early stages. .

Okay, thank you. And then my follow-up question is for the partner program with Bioverativ, just wondering I know your competitor actually moving very fast trying to go to the clinic by the end of this year.

So just wondering can you provide us some update beta thalassemia sickle cell when should we expect the IND filling for that two programs?.

Thank you, Gena. And we are delighted that Bioverativ has now been launched and we have a great partner there that shares our enthusiasm for this program. We are completing preclinical work with them and hope to have the IND submitted very soon..

Okay, thank you very much. .

Our next question comes with Whitney Ijem with JPMorgan..

Hey guys, thanks for taking the questions. I guess first one is just a follow-up on the Bioverativ question.

Can you guys I guess give us any additional color on kind of what are the rate limiting steps for getting that IND in? And then I guess you said very soon, is that like a first half of the year event or before yearend event, any additional color you can give there?.

I would love to, but we are -- it’s the simple blocking and tackling of an IND, all the different preclinical studies that you need to have ready. I am enthused; you saw the zinc finger results for this particular target which I think look wonderful.

We are really enthuse by this and we hope to do it soon, I can’t give you any more details on the timing..

Okay, fair enough. And then another question that I have asked before, but I’ll ask again, just to make sure nothing has changed.

But, as you think about keeping us up to date on what’s happening with the clinical trials ongoing this year, do you plan to kind of let us know when you treated the first patient or when you progress the next dose cohort or anything like that, that we’ll be able to use to sort of track progress or should we expect radio silence until first data?.

That’s a good question and it’s an interesting balance between our enthusiasm to share with you as much as possible and the excitement of treating the first patient with in vivo genome editing and giving you data that is truly meaningful.

Ed what’s your thoughts?.

So, we’ll -- to Sandy’s point, we will announce the first patient in and we as he mentioned that is a seminal event, but as we continue to enroll patients we are going to be reviewing the data.

But as was mentioned we’re going to be providing updates when we have clinically relevant data in hand, which will be either at the end of this year or early 2018..

Okay, got it. Thanks, I’ll hop back in queue. .

Our next question comes from Charles Duncan with Piper Jaffray..

Hi, guys. Thanks for taking the questions. I too had some questions on the clinical program, but love the organization of the call thus far.

Wondering, as you think about sequentially about how the clinical story builds, which of the four programs do you believe could read out some of that clinical relevant data and would that be from like the first cohort or the second one, what do you anticipate in terms of how you would define clinical relevance for those programs?.

Charles, thank you for your question. We are -- this is a very exciting time for this company, because we are blessed with having four programs going into the clinic and there is not many companies have at once and anyone of them could produce clinical data by the end of 2017 or at the beginning of 2018.

Ed what would you regard as clinically relevant, what kind of things are you looking for in the clinical trials?.

Yeah, I mean for the Phase 1/2 trials first and foremost it’s about safety, but we are also fortunate across all of these programs to have a blood biomarker that’s correlated with clinical outcome. So in the example of hemophilia A, hemophilia B at factor level for MPS I and MPS II you have IDUA and IDS respectively as well as urine GAG.

So what success looks like across all of these studies is both a safe dose and a dose that's providing therapeutic protein levels where we expect to see clinical benefit. .

Okay that's helpful. And then moving perhaps a question for Mike. Mike mentioned several points of technological innovation, and I guess I'm wondering if you anticipate any new innovation to be incorporated in say for a second generation candidate for any one of the current envisioned clinical program. So hem A or B or MPS I or II. .

That's a good question and something we even spent some time discussing yesterday as management team. The timeline between having a great scientific idea and getting it into patients into the clinic is around three years generally, by the time you have done the IND and the trial started.

So we have to be sure that the product that we're taking into clinic now is good and we believe that we are taking something that is safe and effective and to patients just know.

But we also have to start to plan for the next generation, we now think that we have the ability to target any nucleus types in the genome and to do it with off-target are driven down to below the levels of detection at clinical scale and the relevant tissues.

But Mike you continue to dream about what's next, don't you?.

Absolutely. And as Sandy mentioned, we had a discussion about this yesterday where as you can see from the data we continue to look at ways to improve the efficiency as well as specificity of the technology and that we've expanded our use of delivery technologies such as use lipid nanoparticles to continue to I think really expand our capabilities.

And that's reflected in both the gene knockout data as well as our ability to perform target integration where in the case of LNPs they really allows us to do two things, where obviously we stopped it isn't sensitive to be present the preexisting antibodies as well as this flexibility to allow us to dose to affect.

And so I think there are a lot of exciting potentials for the generation of sort of improved or second generation products both for sort of I think new applications that we're currently working off as well as the current programs that we have in the clinic. And so this is something that we're continuing to look at….

But Mike that could include, can we do it quicker so the current generation we can get good assets within two weeks. And then good clinical standard assets within two to three months. Should we try and do it quicker.

Can we try and include other enzymes other than one into the zinc finger? Do we look at transcription or editing, so there is a range of things and places we can go with this technology that is very exciting..

Yes. .

That's very helpful. But just to specifically ask the first generation candidates that you're taking into the clinic right now. In the absence of any clinical data and I know that this is partially speculation on your part, but you see these as optimized clinical candidates that if they show safety and efficacy could get all the way to the market.

There is no need for innovation at least for second generation compound at this point?.

Okay to answer that question specifically, we specifically and deliberately believe that these are good safe and efficacious and we are happy to move them into human clinical trials. And if they succeed we will develop them to a registration and launch..

Okay. that's helpful. Last question on the pediatric disease designation, Sandy first of call congratulations on that, happy that you're going to also apply for MPS II.

But could you help at least me understand I don't fully understand how that could into is that set up possibly pediatric disease voucher should that candidate get over the goal and be FDA approved..

Ed do you want to take to that..

Sure yes, so the RPD designation, if we do get approved we would have a voucher granted, which as you know is transferable and the -- we have filed for similar designation in MPS II..

Okay, that’s helpful. Thanks for taking my questions. .

Thanks Charles..

Our next question comes from Ritu Baral with Cowen..

Good morning guys, thanks for taking the questions.

I wanted to ask you about what doses you are thinking for SB-525? I mean going to slide 10, you with the preclinical data the nonhuman primate data highlights the potency of your code on optimize drug versus the others when BioMarin at least potent authority had challenges because of high potency if anything.

So wanted to know what you guys are thinking about dose ranging, if there is any challenges that’s having relatively ultra-low doses or what have been traditional gene therapy of dose level?.

It’s a great question, it’s an important question, because it talks to patient’s safety and the clinical utility of these programs. And I’ll ask Ed to speak to this. It isn’t just about efficacy, it’s about predictability, I think that’s the BioMarin challenge that they have at the moment rather than whether they are efficacious or not.

Ed do you want to talk, how we are going to think about this..

Yes, so I always strongly echo your sentiment about what we’re looking for as tighter expression, I think when looking at the BioMarin data they are getting highly variable data that’s at peak levels where even above 300% and consequence might have been that they were going to 60-13 [ph] dose levels.

As we have presented at public meetings, we believe our data supports the starting dose in the E11 range. And we built into the protocol even an ability to step down to lower dose levels.

The consequence I think of being able to start at a lower dose level means not only that you need a more potent construct, which is what we believe we have but you are also able to have less immune response and the consequence of the immune response maybe what’s driving some of the variability that’s been observed with the BioMarin data.

But by starting at a lower dose and mitigating that potential for immune response we expect and hope to see a tighter control of expression at the factor levels for SB-525..

Got it. And Ed is there any sort of number that you have in your head for clinical data release.

What would be meaningful to you either a specific number of patients say for hemophilia B just for arguments sake or a specific follow-up period where we could look at measurements like would three months be meaningful to you or would we really have to wait for six months in your mind to see the full fruition of efficacy?.

Yes, I mean it’s fairly multi factorial. Again safety is paramount here. We also want to be looking at levels and be looking at are there transaminase elevations that require the use of corticosteroids how long is the corticosteroid course. And what if any is the impact on pharmacodynamics through dynamics in terms of using steroids.

So it’s challenging to use one of those parameters and identify what I would use that to say what’s clinically meaningful. I think as we look at other programs out there, they are generally hitting their stable ranges in around the three to four months' timeframe.

So I think that’s the reasonable estimate in terms of when we might expect to see plateau levels, but of course there is (Inaudible) says when that hasn’t happen.

So for us the most important thing is to be following these patients closely, looking at their factor levels and their safety in real time and then making a determination when we think it’s prudent to disclose that information publicly. .

Got it. And the last question on the enrollment for your hemophilia B program.

Can you talk about what maybe challenges you're seeing to-date, is it with screen failures, or is it with patient interest and caution, how do you describe that?.

So we haven't given details on that we have screened several patients. We have and this is a small patient population there are already very good data from Spark out there. And so it's competitive, I'm confident with what the team are doing will lead us to recruitment of patients. .

Got it, thanks for taking all the questions. .

[Operator Instructions]. Our next question comes from James Birchenough with Wells Fargo Securities. .

Hi thank you for taking our call. This is Yannin [ph] in for Jim. First we have a few questions on the MPS I program and then we have a few follow-up on the early data phosphate ablation that you just talked about today on the call.

So for MPS I, so could you talk about in terms of starting dose, would that program have a compared to the hemophilia how would the starting dose differ will it be higher or lower? And perhaps as part of the consideration for that parameter, do you have some comments on the percentage of liver cells that needed to be modified to achieve a clinical benefit in MPS I compared with hemophilia.

Whether more level cells or lower or a percentage that in your mind you need to transplant?.

So that's a complicated question, it’s a good and complicated. So we haven't revealed what dose we are going to -- we start any of the zinc fingers into the albumin locus programs we’re going to cover hemophilia B, MPS I and MPS II. They will be a similar dosing level.

But your second question is do we look on a different degree of editing as being required for MPS I versus hemophilia.

Mike do you want to talk about that?.

Certainly. I think obviously much of our data was collected from our preclinical studies in mice and this was data that we've shown at the world symposium. Essentially we're using the same doses of AV in our preclinical studies as for the MPS I and II programs as with the hemophilia program.

And based off this we're seeing similar levels of editing, and we see we can achieve super physiological levels of enzyme production from the lever and that this seems to be sufficient for being able to reduce gag levels in the secondary tissues.

So we don't have any firm data in terms of what are the requirements for the levels of genome editing we need to achieve. But we have certainly seen similar levels of editing that provide essentially levels of enzyme that can reduce gag levels and provide at least normalization of gag as well as other sort of standard endpoints that we collected..

That's absolutely right. So we'll be judging the success of this not on a liver biopsy measurement of editing, but on the physiological levels and understanding the consequences of those two patients. .

Got it. And in terms of clinical endpoints for MPS I study. Other than the gag levels, that's listed on clincaltrials.com, could you talk about potential other secondary other endpoints that you might be looking at.

And specifically because I remember you talked about the potential blood drain barrier crossing in your preclinical studies would there be some endpoints that's geared towards looking at implications from potential crossing of the blood drain barrier? Thanks..

Ed do you want to touch on this?.

Yeah, sure so first I think is with regards to biochemical endpoints so you mentioned you are in GAG and that certain because one of them that we’ll be following closely the other for MPS I is plasma IDUA levels and we think this is critical because in patients who are receiving enzyme replacement therapy, we know that there is a plasma IDUA levels are essentially undetectable.

At the trough prior to the next dose of ERT administration. So this should give us a fairly early read to be able to say are we producing IDUA such that we’d be able to detect it at the trough prior to the patient’s dose of ERT.

So that gives us some confidence, if we see it that we are indeed having the ability for the patient to produce the relevant enzyme.

With regards to your second question, we’re looking at a variety of clinical outcome measures, these includes things like six minute walk test, range of motion and some cognitive testing with regards to your question about the brand. The one item that I do want to mention is that….

But you probably don’t expect to see much difference in….

Well and that’s about what I was going to get to, is that these are all adult patients who again if had this disease for years and are likely to have a fair number of fix obesities whether its neuro-cognitive, whether it’s in the six minute of walk test and we will expect the main benefit of this to be seen in children.

We are measuring all these outcome measures, but mostly what we’re going to rely on again in the Phase 1/2 study is evaluation of safety and evaluation of biochemical outcome measures, including plasma IDUA and urine GAG..

Got it, that’s very helpful. So on the phosphate ablation technology that you just talked about is very interesting. I was wondering could you in terms of off target activity and the higher specificity could you compare your findings with the current technology.

I think at the RAC [ph] meeting it was mentioned for example SMPHD [ph] gene was one of the off target genes as an example for the current technology.

So could you talk about in terms of improvement in off target, how does the phosphate ablation compared with current one?.

So, I mean that’s a good question and we have to be sure that the current technology that we’re taking into patients this year we believe is safe and where we as a company have to believe it’s safe. We have the IRB saying it’s safe, we have the FDA saying it’s safe and that the off target is at the right level.

I think what we’re trying to tell you with this story about phosphate ablation and understanding of target is that we can now -- we now understand how our targets happen, with the previous assets we spent a long time driving down the levels of off target.

With future assets we now can predict how those happen and we can systematically and rapidly reduce that without going through the more steam power aberration that we did before. .

Got it, thank you. .

And I am not showing any further questions at this time, I’d like to turn the conference back over to our host. .

Thank you so much for joining us this morning and we look forward to speaking with each of you and meeting with many of you in coming months. Thank you. Have a good day..

Ladies and gentlemen, that concludes today’s presentation. You may now disconnect and have a wonderful day..