Sangamo Therapeutics, Inc. (SGMO) CEO Alexander Macrae on Q3 2018 Results - Earnings Call Transcript

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About: Sangamo Therapeutics, Inc. (SGMO)
by: SA Transcripts

Sangamo Therapeutics, Inc. (NASDAQ:SGMO) Q3 2018 Earnings Conference Call November 8, 2018 5:00 PM ET

Executives

McDavid Stilwell - VP, Corporate Communications & IR

Alexander Macrae - CEO, President & Director

Stéphane Boissel - EVP, Corporate Strategy

Edward Conner - SVP & Chief Medical Officer

Kathy Yi - SVP & CFO

Edward Rebar - SVP & CTO

Analysts

Qian Wang - Bank of America Merrill Lynch

Gena Wang - Barclays Bank

James Birchenough - Wells Fargo Securities

Ritu Baral - Cowen and Company

Whitney Ijem - Guggenheim Securities

Eric Joseph - JPMorgan Chase & Co.

Maurice Raycroft - Jefferies

Operator

Good afternoon, and welcome to the Sangamo Therapeutics Teleconference to discuss Third Quarter 2018 Financial Results. This call is being recorded. I will now pass over to the coordinator of the event, McDavid Stilwell, Vice President of Corporate Communications and Investor Relations.

McDavid Stilwell

Hello, and thank you for joining us. As we begin, I'd like to point out that we will be referring to a slide presentation today. And you may find a link to the slide presentation on our website, www.sangamo.com, on the Events and Presentations page of the Investors + Media section of the site. I'd also like to remind everyone that the projections and forward-looking statements that we discussed during this conference call are based upon the information that we have available today. This information will likely change over time. By discussing 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 discussed today, and no one should assume at a later date that our comments from today are still valid.

These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are detailed in the documents that the company filed with the Securities and Exchange Commission, specifically, our annual report on Form 10-K and our quarterly reports on Form 10-Q. The forward-looking statements stated today are made as of this date, and Sangamo undertakes no duty to update such information, except as required under applicable law. With me this afternoon on this call are several members of Sangamo senior management, including: Sandy Macrae, Chief Executive Officer; Kathy Yi, Chief Financial Officer; Ed Conner, Chief Medical Officer; Ed Rebar, Chief Technology Officer; Stéphane Boissel, Executive Vice President of Corporate Strategy; and Heather Turner, Senior Vice President and General Counsel. And again, we refer to a slide presentation during the call. Those slides are to be found on the Events and Presentation page of the Investors + Media section of our website. And now I'd like to call over to Sandy.

Alexander Macrae

Thank you, McDavid. Good afternoon, everyone. As we approach the final weeks of 2018. I've taken some time to reflect on how far we have come this year. Sangamo is a genomic medicines company, focused on clinical development of novel therapies with the potential to transform patients' lives.

Genomic medicines is a new field with the potential to disrupt healthcare by shifting the emphasis of drug development from treating symptoms to pursuing cures. At Sangamo, we have the fortune of having the experience, the skills and the technology to lead the way. Sangamo is a remarkably different company now compared to the start of the year. We've made diligent progress in our transformation from biosciences to genomic medicines, and we are taking important steps to successfully execute our strategy to develop proprietary portfolios in 3 therapeutic areas: inherited metabolic diseases; CNS conditions; and immunology. We're advancing our clinical programs at MPS I and MPS II and moving our Fabry disease program towards the clinic. We're investing in IND-enabling studies for our zinc finger protein transcription factor gene regulation approach for CNS diseases. And through our acquisition of TxCell, we have the regulatory T-cell expertise to lead the field of CAR-Treg cell therapies for immunological and autoimmune diseases. 2018 is the year Sangamo became a clinical development organization. We have begun to report results for our most advanced clinical trials and we're making strong progress in building our earlier clinical studies and can now see forward to clinical data readouts from multiple programs in the coming months.

As we expect a robust flow in the coming months, I want to remind you of a few important points of leverage across our pipeline. We are using the same AAV vector across five clinical programs. The albumin locus in vivo genome editing approach we're using for MPS II is the same technical approach employed for MPS I and for hemophilia B, a so-called platform within a platform. Success in gene therapy for hemophilia A or with in vivo genome editing for MPS II will have positive implications for the probability of success of other pipeline assets using these same technologies. Today, we have important new progress to share from our most advanced programs. I will focus on MPS I and MPS II, while Ed Conner will lead you through the others, in particular, hemophilia A and hemophilia B. Regarding MPS I and MPS II, the independent Safety Monitoring Committees released two studies convened October to discuss the appropriate path forward for each clinical trial. For SBS -- SB-913, for MPS II, the SMC reviewed the safety and efficacy data collected so far. This includes data for the 6 patients across all 3 dose cohorts in the Phase I/II 2 CHAMPIONS Study, including the high dose cohort at 5e13 vector genomes per kilogram, which was not yet available nearly September at SSIEM when we presented results of the 4 patients from the low and mid-does cohorts. We are extremely pleased with the 3 recommendations the SMC made after reviewing the safety and efficacy data from 3 dose cohorts. They said: one, proceed with cohort expansion at the 5e13 dose of SB-913; two, begin enrollment of adolescents into the study at the 5e13 dose; and three, initiate ERT withdrawal procedures for appropriate patients. We now expect the proto -- the pace of enrollment will now accelerate as the cohort expansion phase is not limited by earlier sequential dosing groups, and we'll be able to infuse the next 3 patients almost simultaneously.

We are eager to take the step of enrolling adolescents as this is progress towards treatment very young children with MPS II, who we believe will benefit in most with SB-913. And we're also very excited with initiation of ERT withdrawal under protocol guidance. We remain on track with all our other activities, including the more sensitive assay development we spoke of previously, and expect to have more information to share with you early next year.

Regarding the Phase I/II EMPOWERS study evaluating SB-318 for MPS I, after reviewing the safety and efficacy data from the MPS II trial and the first patient in the MPS I trial, the committee agreed it was appropriate to enroll the next 2 MPS I patients into the high dose 5e13 vector genomes per kilogram. The rationale for this was clear and sensible, i.e. given the encouraging safety profile for AAV6 demonstrated so far, the safety committee felt comfortable moving to third dose. And secondly, given MPS disease biology, producing more enzyme is always better for the patient. Accordingly, the second patient in the EMPOWERS study was recently dosed at 5e13 vector genomes per kilogram dose that was recommended by the committee. We are pleased with their recommendation for SB-318, as it allows us to accelerate patient recruitment in the study.

Later in this call, you'll hear from Ed Conner, Chief Medical Officer, who will share details of progress in the other clinical programs; and from Kathy Yi, our CFO, who will provide a financial update for the third quarter. But first, I'm very pleased to introduce Stéphane Boissel, who was CEO of TxCell prior to the acquisition and has joined Sangamo as Executive Vice President of Corporate Strategy. Stéphane brings over 25 years of experience across corporate finance, strategy and business development. And I've asked him to help us realize our strategic vision and build Sangamo into the premier genomic medicines company. Stéphane?

Stéphane Boissel

Well, thank you, Sandy, I'm very excited to join the team. Over the past few years as CEO of TxCell, I studied the genomic medicines landscape closely. As I knew that genome editing technology would unlock the future of our CAR-Treg technology. Sangamo stood apart from the field as the company's zinc finger platform is to me technology the most advanced and the most flexible and because of Sangamo's strong intellectual property portfolio around the zinc finger nucleases. We at TxCell are pleased to join Sangamo. And I can say that the integration is going very well. And I know that the team in front is excited to have full access to events and to Sangamo's expertise to advance our CAR-Treg platform in the autoimmune space. I myself was intrigued by Sangamo's opportunity to lead the way in the field of genomic medicine and also by Sandy's vision to change medicine for gene editing. It is rare to see a company with such potential, and I'm excited to be a member of the team. I'm so excited that I'm in the process of relocating from France to San Francisco, actually.

It has been only a few weeks since I joined the company, and there is obviously still much to learn and do. In the coming months, I will be focused on strategy and planning for Sangamo's evolution into a fully-integrated biotechnology company. Our goal is to become a global organization, leading the development of genomic medicine in 3 elected therapeutic franchise i.e. inherited metabolic disease, CNS and autoimmunity, but also to build a strong pipeline of assets under each one in order to extend the therapeutic potential of our technology in as many arrestable diseases as possible to treat eventually as many patients as possible. Our future is going to be both the combination of internal and partner program. With respect to strategic partnering, we will pursue a pragmatic approach for both the elected therapeutic franchise and for field of medicine outside of this focus.

We will consider partnering our technology or program only when we believe doing so will maximize shareholder value and accelerate the delivery of our genomic medicine to patients. In short, when we believe a third party is in a better position than us to reach out to patient and to maximize the potential of our assets. There also are ancillary technologies that are come to our effort, and we will continue to develop those in us or to acquire them when that is more efficient. And finally, we will continue to plan for future commercialization. Our field is a new one and genomic medicine with such a large therapy potential, this serve a new commercial model. One that, of course, will have to be appropriate for all stakeholders, including patient, payors and physicians. With that, I'll thank you, and I'll turn to Ed for a clinical update?

Edward Conner

Thank you, Stéphane. And hello, everyone. Sandy earlier provided the update on the MPS I and MPS II trials, and I'm going to focus on progress in our other clinical pipeline programs. I'll begin with an update from our SB-525 gene therapy program for hemophilia A. The dashboard for this program is on Slide 11.

In October, the independent SMC for the SB-525 Alta study met to review accumulated safety and efficacy data from the 6 subjects enrolled to date. As of that review, SB-525 continues to be generally well tolerated with no treatment-related serious adverse events and no use of tapering courses of oral steroids. Importantly, we continue to see dose-dependent therapeutic efficacy on factor levels in the serum. The SMC recommended that the study continue with an additional dose escalation, which we also strongly agree is the right next step. For the pivotal trial, we want to find the dose that balances the highest factor levels with an appropriate safety profile and low immune risk. We're excited that the SB-525 safety profile allows for continued dose escalation as we want to develop the gene therapy that best suits the needs of patients with hemophilia A. This is a field of competition, and we do not believe that others have yet presented data that would support an optimal product profile for hemophilia A gene therapy. For SB-525, I'm very encouraged with the safety, the lack of immunogenicity and the dose-dependent effect observed so far. We believe with this continued dose escalation, SB-525 has the potential to be a novel therapeutic approach for hemophilia A that is very well positioned among other gene therapies in development. We and Pfizer now plan to present safety and efficacy data from the Alta study only after dose escalation is complete and the clinical trial is progressing to the cohort expansion phase. Accordingly, we made the decision last month not to submit a late-breaking abstract this year to ASH.

Regarding our SB-FIX Phase I/II 2 clinical program for hemophilia B on Slide 14, I'm pleased to announce our team has made tremendous progress turning around this study. We've identified eligible patients for enrollment and expect to dose the patient very soon. And this will be at the 5e13 vg/kg dose, the highest dose now used in the other albumin locus in vivo genome editing programs. Indeed, as with MPS I and MPS II, the Safety Monitoring Committee of our hemophilia B program reviewed available AAV and ZFN safety and efficacy data from other clinical trials and determined that enrolling patients directly into the third dose cohort is the right step forward for the SB-FIX study. As with MPS I, the rationale to move to the high dose was based on the encouraging safety profile observed today, which allows us to go to a dose of SB-FIX that has greater potential to result in higher clotting Factor IX levels. Additionally, we've initiated clinical sites for the SB-FIX program in the U.K. and are actively screening patients for enrollment at those sites. I'm encouraged with the pace of progress the hemophilia B team made in the third quarter and look forward to providing further updates about this program on subsequent calls.

Turning now to our ST-400 gene edited cell therapy program for beta-thalassemia on Slide 15, which is been developed with collaboration of Bioverativ, a Sanofi company. We expect to enroll a second patient into the study by year end and to have data available in 2019.

Regarding BIVV-003 for sickle cell disease, startup activities are proceeding and Bioverativ expect to initiate the first clinical site this year.

Finally, very brief updates on ST-920, our gene therapy for Fabry disease and TX200 our CAR-Treg program for solid organ transplant. With both, we remain on track for clinical trial initiations in 2019.

Patient recruitment for our in vivo genome editing programs has accelerated. Patients are excited about participating in our studies, and we've now established a strong recruitment pipeline across all of our active Phase I/II clinical trials. We have 5 ongoing studies hemophilia A and hemophilia B, MPS I and MPS II, and beta-thalassemia. And we have 3 more heading into the clinic soon, including sickle cell disease, Fabry disease and TX200. In addition to updates and results from these programs, we also look forward to providing details about the work we are doing with Kite to advance next-generation allogeneic immune oncology cell therapies. This is an incredible time for clinical development at Sangamo. I'll now turn the call to Kathy for a financial review. Kathy?

Kathy Yi

Thank you, Ed, good afternoon, everyone. The press release we issued earlier this afternoon includes detailed financial results for the third quarter of 2018, which are summarized on Slide 17. We ended the current quarter with $459 million in cash, cash equivalents and investments. And we're maintaining our previous year-end cash guidance of $380 million. As of October 1, we successfully completed the first stock purchase of TxCell ordinary shares, which represented 53% of the share rights of TxCell. And on November 1, we launched a simple tender offer to acquire the remaining ordinary shares. We expect to complete the tender offer before the end of this year and to release TxCell from the French stock exchange. Since the beginning of October, we have started integrating TxCell operations into Sangamo and look forward to developing the next generation CAR-T cell therapy for autoimmune diseases through the synergy of our ZFN gene editing technology.

Our operating expense for the third quarter of 2018 was $39.8 million, including R&D cost of $28.8 million and G&A cost of $11 million. The increase of $10.4 million in Research and development cost versus prior year is mainly driven by manufacturing and clinical trial expenses, as we move further into the clinic. The G&A increase is primarily due to general support of the growth of our pipeline and clinical programs as well as onetime transaction costs associated with the TxCell acquisition. At year-end, we expect our 2018 operating expense to be in the range of $160 million to $165 million, inclusive of TxCell acquisition. The total net loss for the third quarter of 2018 was $12.8 million or $0.13 per share, basic and diluted, compared to $12.4 million or $0.15 per share, basic and diluted, for the same period in 2017. Revenue for the third quarter of 2018 was $23.6 million, which reflects an $11.8 million increase from the same period in the previous year. This increase is driven mainly by $9 million revenue from the Kite collaboration agreement, including reimbursement of $2.7 million in research services. As a final comment, we expect our cash runway to be approximately 2 years, taking into account the expansion of our autoimmune pipeline and further investments in our lead assets for MPS and hemophilia B in preparation for pivotal trial readiness. We believe we are in a strong financial position to continue to advance our extensive pipeline of genomic medicines, and we're very much looking forward to reporting our continued progress. And with that, I'll turn the call over to Sandy for closing remarks.

Alexander Macrae

Thank you, Kathy. Before I turn the call over to questions, I'll conclude by saying what an exciting time this is at Sangamo as we solidify our transformation from an early biosciences focus into a leading genomic medicines company. In the last 2 years, we've made critical investments in people, in technology and in development, and we are now beginning to see the results of these efforts as we establish our clinical pipeline, which we believe to be unrivaled among gene therapy and gene editing companies. I very much look forward to the flow of clinical data in 2019 and beyond. And so we'll now turn to your questions. Operator?

Question-and-Answer Session

Operator

[Operator Instructions]. Our first question comes from Qian Wang with Bank of America Merrill Lynch.

Qian Wang

So I have a couple, if I may. The first question is actually on the MPS II program. So just curious like what is the consideration for these dose expansion decisions from the committee? Is it mostly on safety? And -- or it's also on the efficacy? And what kind of data they have seen so far do? Do they see GAG reduction, plasma, enzyme, biopsy with a certain dose cohort? Could you please just clarify on that?

Alexander Macrae

So that's a very fair question, and I wish I could answer it more completely. But they see all the available data for safety and whatever efficacy data is available at that time and then they make a decision based on the benefit risk of the product and where they see the development should go. We will share the results with the broader community sometime in 2019. And until then, we're not able to comment on individual parts of the equation.

Qian Wang

Got it. And you said that they recommend on taking off the ERT and in appropriate patients and under protocol guidance during your prepared remarks. I'm just curious what that really means? Does that mean that's still depending on the consent from the physicians and the patients?

Alexander Macrae

So the SMC makes a recommendation we always talk -- we talk regularly with the various investigators, it's a small study there's very few investigators. They are very pleased with what they have seen so far. But then, it's a discussion between them and their patient about when and how they stop the ERT. I added under protocol guidance just to give everyone reassurance, that this wasn't each one doing it their own particular way. That there is a standardized way across each of the patients for the data that will be collected.

Qian Wang

And lastly, if I may. On the hemophilia A I think a lot of investors are really expecting to see an abstract on November 1, which we didn't see. It's clear now you say that is because you decided not to submit for LBA. Just curious what is driving that decision? Is it the durability of the patients or you don't see a similar level of expression with the six patient? Or given the FDA guidance, you were thinking about I mean, the normal range rather than 12%? Can you just clarify, please?

Alexander Macrae

Ed, can you deal with this one, please?

Edward Conner

Sure, yes, so we're very excited with where we are. And as I said, earlier on the call, safety allows us to dose escalate. And in terms of items that you were talking about, as we talked about earlier before, we're continuing to see factor levels that are in the therapeutic range. We know that with our safety being as it is, and again just as a reminder, we haven't seen any patients who have had to take tapering courses of steroids. We've seen no drug-related SAE's. So given that, we do recognize with that with recent FDA guidance, they're is the possibility of accelerated approval with factor levels that are in the normal range. That and our discussions with our partner Pfizer, we want to release the data when we've -- when we are at the levels that would be going forward with in our pivotal trial.

Qian Wang

Is that fair to say that you're aiming for normal range right now?

Alexander Macrae

No, we're looking for the right balance of efficacy and safety. We want also to collect data that will allow us to make a good decision to go into Phase III and give the data time to mature, because in the end, the most important thing isn't to release a patient-by-patient but it's to get into Phase III and get it to patients as quickly as possible.

Operator

Our next question comes from Gena Wang with Barclays Bank .

Gena Wang

I think I'll basically follow the similar line, the prior question. So regarding the MPS II, just wondering did you see any SAE in Cohort 3? And what makes you decided to dose expansion instead of dose higher?

Alexander Macrae

So we haven't seen any SAE's in Cohort 3, and we continue -- thank you for asking because we continue to look at the safety that's treated very seriously. It's an SMC decision, and they see the available safety and efficacy data. The protocol allowed for 3 cohorts, so 5e13 is the third cohort, and we -- and if you remember there's only 2 patients in each cohort as well, so the expansion will give us more data the 5e13 level. And then, we hope to present a more holistic view of this at the beginning of next year.

Gena Wang

Okay. So then for the expansion cohort, how many more patients are you planning to enroll? And then, is there a step that you will be also thinking to dose higher based on the efficacy?

Alexander Macrae

So we would -- we are likely -- we are able to dose another 3 patients and as I said, we can dose them almost similar simultaneously just a matter of logistics. The SMC will then review the data and it interviews on a regular basis. And it will make a decision whether this is the right dose level or whether it needs to go to a higher level.

Gena Wang

Okay. And then -- Sorry.

Edward Conner

I just wanted to clarify one thing, that third cohort, there was an SAE, but it's not treatment related, so just clarifying that.

Gena Wang

Okay. Okay. And then, another question is regarding hemophilia A, just wondering, what is the first cohort dose? I know like you share with us the doses for MPS programs. And just wondering what's the reason not sharing the hemophilia A doses?

Alexander Macrae

Because it's a much more competitive space and each of the 3 companies is trying to position themselves as having the most competitive product. And that's why we're so pleased that the safety in our hemophilia A product allows us to dose escalate to this level. And the fact that we've had no long-term tapering doses off steroids, allows us to balance both the efficacy and safety to, we think, have the optimal product.

Gena Wang

Okay. Just one last question. So what will be the bar for you to stop dose escalation for hemophilia A and then move to expansion phase?

Alexander Macrae

That would be something that the SMC will advise on, and we and our partner, Pfizer, who will take over for the Phase III study will agree together.

Operator

Our next question comes from James Birchenough with Wells Fargo.

James Birchenough

Congrats on all the clinical momentum. So on MPS II -- I know when you came out with the data initially and we saw the impressive urinary GAG reductions, but not really any enzyme level there was the thought that maybe the blood compartment might not be the right place to look for enzyme. And so just wondering with additional experience, is that still your view? Or have you interrogated other compartments? And maybe you could give us an updated thought on that?

Alexander Macrae

So when we last talked about this, as you say rightly, we saw really impressive and consistent reductions in GAG in Cohort 2. We weren't able to report any changes in IDS. And what we discussed was the idea that it was being released from the liver and quickly taken up by the tissues and that was why there was an effect, because it was an enzyme effect, there was an enzyme, there must've been editing. And I think we're still in a very similar place with that. The team have done remarkable things in the past few months to look at new ways of measuring enzyme and GAGs and increasing the sensitivity of the assay and am very pleased that we will be able to talk more about that in the coming year, hopefully early next year, and give them a more holistic report on it. Our experience talking to analysts like yourself is those of you who have followed our story closely, understood the GAG effect and felt that it was representative of editing having happened. And we realize that there are others that will need the other pieces of the puzzle and so what we're try and do is hold on and come back next year with as many pieces as possible that will allow others that haven't followed us as closely as you have, Jim, to understand the effect.

James Birchenough

That's very helpful, Sandy. And then, maybe, a question for Ed. Just on the beta-thalassemia program and as we look ahead to sickle cell disease any ex vivo gene therapy or gene editing, in general, one of the things we've seen as a potential explanation for lack of durability of effect is not transducing pure stem cells but actually, transducing cells that are already differentiated and aren't self-renewing. So can you speak to the vector you're using and whether you think it transduces the right cells better than others? Because I think that's becoming important.

Edward Conner

So we're using electroporation to transduce with our mRNA. We've seen, and Ed Rebar the other Ed who has presented on that data previously, but we are very pleased with the cell yields that we're getting and the percent of edited CD34 stem cells as well.

James Birchenough

That's helpful.

Edward Conner

And Ed if you want to add to that?

Edward Rebar

Perhaps, 1 additional comment to add is that the type of modification we are doing, which is NHEJ-mediated knockout, that's a modification that -- okay, I know your question pertained to delivery, but there's a whole set of things that come into play, including does your modification occur optimally in those types of cells too. And I think NHEJ people have generally recognized if that occurs, that seems to be something that will occur fine in that cell type as opposed to HDR-type processes, which I think, are a little bit more -- a little bit less -- harder to get to go let's say.

James Birchenough

So that's helpful. Maybe just final question on hemophilia A. Do you expect to get at ASH on the competitive landscape and what a true competitive profile will be? I guess, when we've asked in the past on what you think a competitive profile is? I think it's yet to be determined. Do you think we'll get better clarity? And is that part of the consideration in waiting to get a fuller data set, seeing what others are showing as well?

Edward Conner

Yes, so I would say the short answer is, no. Because the other folks aren't either presenting any data or aren't presenting their high -- this cohort data, reflecting the competitiveness of this area.

James Birchenough

Do you feel like you have a good sense of what the proper benchmark is? As we look to the fuller data set, do you feel like there is a clear benchmark to have a competitive profile?

Edward Conner

I feel like there is a benchmark. But as I said on the last call, we can't overlook safety. Safety is critical and not just from the standpoint of having to take steroids but the monitoring that may be associated if you're having pretty significant immune reaction. So it's really the combination of the 2.

Operator

Our next question comes from Ritu Baral of Cowen.

Ritu Baral

My question is on 913 and 318. 318 is going to be dosed at the same dose, the 5e13, as 913, is there any differential PK or more specifically, PD of the enzymes in the 2 -- deficient enzymes in the two conditions that should lead us to believe that the doses should work differently in the two diseases as far as GAG reductions?

Alexander Macrae

I think that's a level of sophistication that the clinical signs around this hasn't got to yet. So we are treating them similarly and it's only through doing this experiment that we'll be able to understand whether there are subtle differences in the PK/PD from these. As I said on the call, what we take from the SMC decision and what they've said to us is the highest safe dose is the sensible one to use because we want the patients to have as much enzyme as possible. We were delighted with the reduction in GAG in the cohort to patients in MPS II and we look forward to showing the world the Cohort 3 data and the data from MPS I when we have collected all together and made a, hopefully, compelling story.

Ritu Baral

And then, moving to 525, your hemophilia A program. You mentioned that you didn't want to unveil data until you had followed patients for a meaningful amount of time. What is that meaningful amount of time? Just given focus on durability of these gene therapies, especially the AV gene therapies? What is the right amount of time? And when do you think that a complete data set will give you a good idea of the durability of your -- of 525?

Edward Conner

So we're not commenting on what the overall durability we're looking at, I mean, if you look at it from the patient perspective, of course, they want to see long-term stability in terms of the factor levels. And I think again, it's not just that the factor levels go up and stay up, but they're not varying even sometimes up to a high toxic range. And so it's really looking at the whole curve and understanding how the factor levels are performing week-to-week, month-to-month. It's consistency really at the end of the day.

Ritu Baral

Got it. And then for some other AV rare disease therapies, we've seen sort of an inconsistency of response across patients within a cohort. I mean, obviously, I'd love for you to comment on consistency of response across the cohorts that you've seen but barring your ability to answer that, can you comment on that pattern that we have seen? And whether you think that's a reflection of patient selection? Whether you think that's a function of the drug itself? Or just dose?

Alexander Macrae

Can I have a go at this. There are so few data points between the studies and within a study to be able to see anything meaningful, because all view are different factor and a different construct, and we screen our patients in the ways that we don't share with each other. But if I try and pull back a little from this and think of it, because I'm a physician, and if I was thinking if I'd want to treat a patient, it isn't about a certain number. It's about knowing that the medicine was a safe as possible and I wouldn't have to worry about the patient getting long courses of steroids. But knowing that I could predict what dose was appropriate for the patient, so that's speak somewhat to your -- the within-a-cohort predictability and consistency. And then, it's about knowing that once I give the patient the medicine and they have a certain level of factor that it stays with them for a meaningful period of time, for years. And I think those are more important than focusing our obsessing on a number. It's about safety, predictability and consistency.

Ritu Baral

Got it. And then last question. Just -- how to look at the competitive space in beta-thal right now? Obviously, you have bluebird. You have some other alternative mechanism therapies moving forward. What do you think you can bring to the table to address the unmet need in beta-thals that others couldn't?

Edward Conner

Yes, I was going to say first. I think I mean, it's exciting for patients that so many companies are trying so many different approaches. Why I am so excited about our approach is the level of editing we've seen. The no detectable off-targets, our manufacturing process, all of those I think, in my view, lead to a very robust product and, at the end of the day, that has the greatest potential, at least in my view, to help patients. I think as we look long-term, the precise editing that we're doing at the erythroid-specific enhancer of -- will, I think, not only provide the precision and specificity that we're looking for but in contrast to other approaches where they're doing random integration, I'm also very excited about the long-term safety products of our approach compared to some of the others that are currently out there.

Operator

[Operator Instructions]. Our next question comes from Whitney Ijem with Guggenheim.

Whitney Ijem

First one is on hemophilia A. Regardless of what you're targeting, I guess, in terms of product profile, based on your preclinical work, is it your expectation that you could get there with the fourth dose cohort or is there potential to have to go to additional cohorts beyond that?

Alexander Macrae

We are living one cohort at a time and we will gather that data the safety and efficacy and present it to the SMC.

Whitney Ijem

Okay. And then for MPS II, you spoke about kind of looking for new ways to measure enzyme in developing more sensitive assay. And sorry if I missed this, but are any of those in practice now and has the SMC seen any of that data?

Alexander Macrae

We are not commenting on when they will be ready, but I want to give you assurance that, that process of improving on the assay is working well.

Whitney Ijem

Okay. And then, just last one, as we think about kind of additional data disclosures from other programs coming up in the next year or so, can you just help us understand how you think about sort of the materiality of clinical updates and kind of whether or not we could see similar changes in timeline as we look to additional updates in 2019?

Alexander Macrae

I think we learned from the MPS II data. It's most useful to present the data when the story is as complete as possible rather than our excitement -- my excitement, because I'm accountable here for this, to share what we thought was really groundbreaking data that showed the GAG level reduction. And so I think you'll find as, and I think you will see from this conference call that we will present data when it's a complete story and it helps everyone understand the benefit this has to patients.

Operator

Our next question comes from Eric Joseph with JP Morgan.

Eric Joseph

I really just had one. I wanted to follow up on the earlier question on MPS II and get your thoughts on the utility of liver biopsy in determining whether editing is taking place and sort of filling in some of the pieces of the puzzle, as it were, for that program? And whether, liver biopsy is something patients, one, are willing to undergo, and whether that type of data is something that's on the table when you're updating the program next year?

Alexander Macrae

So liver biopsies are invasive, so patients have to choose to have them and not all patients will have a liver biopsy. They're difficult to do, particularly in these kind of patients. We will share whatever data we have and hope to construct a story with all the different bits in it that would help people underpin the reduction in GAGs that we reported earlier this year.

Operator

Our next question comes from Maury Raycroft with Jefferies.

Maurice Raycroft

I'll be quick. I just have two quick questions. For MPS II, just wondering if you can comment -- and so the SMC met in October. I'm wondering if we can get -- clarify on whether the ERT has been withdrawn yet, if that decision has been made for any patients?

Alexander Macrae

We said earlier that we wouldn't reveal the days that the ERT could be withdrawn, is withdrawn, was withdrawn, because we want to make sure that we have solid data to be able to present so as everyone can understand that.

Maurice Raycroft

Got it. Okay. And then just for hemophilia. For the next dose level, will you use any steroid with that dose?

Edward Conner

No, it will be the same approach that we have taken before where patients are not given prophylactic steroids.

Operator

[Operator Instructions]. Our next question comes from Qian Wang of Bank of America.

Ritu Baral

I just have a quick follow-up. So it's encouraging that you guys see the safety profile with all these gene editing programs. For example, like the MPS I you were able to skip one of the dose. So I'm just curious because initially, you wanted to evaluate three doses. So is that possible they will go higher than the 5e13?

Alexander Macrae

So we have the protocol is for three doses and the SMC have asked us to expand the cohort then we will present them all of the available data for that and they'll make the -- help us make the decision about whether this is the right dose or whether something else needs to be done.

Qian Wang

Yes, I'm talking but MPS I, not MPS II?

Alexander Macrae

It's the same there, so the MPS -- and we -- the MPS Safety Monitoring Committees overlap, so there are some people that are on both. So they are aware of what's happening on the other one because they're very reassuring and informative.

Qian Wang

Yes. And can you just remind us initially, how do you decided to choose these 3 doses?

Edward Conner

So that doses were chosen based of the preclinical work that was done and also, of course, in discussion with the FDA.

Qian Wang

Yes, is there a feeling that people generally are thinking about from the FDA, for example, given we have heard some of the noises in terms of a high dose and that kind of signal?

Edward Conner

It is very program dependent and very vector dependent.

Operator

Our next question comes from James Birchenough of Wells Fargo.

James Birchenough

Just quickly, I just want to confirm the cohort expansion for MPS II, I just want to confirm that it's not related to the SAE that was not drug related? Sometimes you'll get a cohort expansion to get more experience around an adverse event. I just want to make sure that, that wasn't the reason for the cohort expansion?

Alexander Macrae

Absolutely not.

Edward Conner

Right, it was not.

Operator

I'm showing no further questions in the queue. I'd like to turn the call back over to Sandy for any closing remarks.

Alexander Macrae

We would like to thank everyone for their interest and continued support and look forward to talking to you again in the new year. Bye-bye.

Operator

Ladies and gentlemen, that does conclude today's conference. Thank you for participation and have a wonderful day. You may all disconnect.