Sangamo Therapeutics Inc (SGMO) 2018 Q1 法說會逐字稿

Good morning, and welcome to the Sangamo Therapeutics teleconference to discuss the first quarter 2018 financial results. This call is being recorded.

I will now pass you over to the coordinator of this event, McDavid Stilwell, Vice President of Corporate Communications and Investor Relations.

Good morning, and thank you for joining us. As we begin, I'd like to point out that we'll be referring to a slide presentation today. 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.

I'd also like to remind everyone that the projections and forward-looking statements that we discuss during this 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 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. 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 morning 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; Michael Holmes, Chief Technology Officer; and Heather Turner, Senior Vice President and General Counsel.

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 site. Now I'll turn the call over to Sandy.

Thank you, McDavid, and good morning. Since our last conference call, we have made strong progress across several key priorities for the year. We completed enrollment to the first 2 cohorts of the hemophilia A gene therapy and MPS II in vivo genome editing clinical trials and expect to present initial efficacy data from these studies in late summer.

We've expanded our leadership team with several key appointments. We opened our first CTA to expand our clinical development to the U.K. And we received an $8 million CIRM grant for the study of ST-400 beta-thalassemia trial. But most significantly, we executed a global oncology cell therapy collaboration with Kite, Gilead, which included $150 million upfront payment.

And in last month, we further strengthened our balance sheet with a follow-on equity offering, raising net proceeds of approximately $216 million. We now have a very strong cash position of close to $600 million. Kathy will provide further details later in this call. But first, I'd like to reflect on what for such financial strength means for Sangamo.

Realizing the full potential gene editing technology will be our journey, and the genome editing applications we're evaluating now are just the beginning. We intend to manage Sangamo for long-term success, and that means we'll make the investments needed to advance on the opportunities that are in front of us now and be prepared for those we believe will come as the future of genomic therapies continues to unfold rapidly.

We will invest to develop products that we own ourselves through to commercialization, particularly in the therapeutic areas of focus in rare diseases in liver, CNS and immunology. We will invest to continue to advance our technology platform and look to retain more of a value of our research and development. Our financial strength will allow us to pursue additional partnerships strategically.

We will invest to create or obtain delivery and other technology to bring us closer to our vision for gene editing that one day, we'll be able to edit any gene and any tissue for any disease. And we will invest to build our manufacturing capabilities to ensure that we control timelines, quality and costs.

Sangamo is evolving rapidly. We're growing to manage the expansion of our pipeline and research. And as we continue to grow and our programs advance, there will be changes to our leadership team, as we've seen recently. And I view these changes positively as they represent advance in both as the company as well as its executives.

The next 18 months hold many milestones for the company. We expect to report clinical data from potentially 7 clinical trials across in vivo genome editing, ex vivo genome editing and gene therapy approaches. We'll advance proprietary and partnered CNS programs towards IND. And we expect to identify and develop initial oncology product candidates with Kite, Gilead. We will have non-human primate data from our tau program. We'll operationalize the enhancements to our core zinc finger technology platform. And we will complete the build-out of our new headquarters in Brisbane, California and in-house GMP manufacturing facility.

I'll now turn the call over to our CFO, Kathy Yi, for a financial update in the first quarter. Kathy?

Thank you, Sandy, and good morning. We've provided details of our first quarter financial results in the press release we issued earlier this morning, and I'll be happy later in the call to answer any questions you have about them.

Sangamo is the strongest it has ever been financially. We're well capitalized with a quarter-end cash balance of $234.9 million and including both the oncology Kite, Gilead $150 million upfront and the approximately $216 million of net proceeds from our follow-on offering that we recently completed in April. We have approximately $600 million in cash and cash equivalents on our balance sheet.

With our strong financial position, we must focus on execution of our current clinical programs, and we're excited by the potential of clinical trial readouts over the next 18 months from 7 development programs.

Before I turn to financial guidance for 2018, I want to make -- take a moment to discuss our corporate strategy, in particular how we plan to invest shareholder capital in product development of our proprietary product portfolio and in collaboration with partners.

Our strategy is to retain and develop product candidates ourselves in certain therapeutic areas that meet key criteria, including having breakthrough potential for unmet needs, where development and commercialization are financially and operationally feasible and where we see synergies across our product candidates and therapeutic approaches.

As we told you on our last call, we have identified 3 therapeutic areas where we're excited about investing for Sangamo's proprietary program. First, in inherited metabolic diseases, where our lead product candidates are focused on in vivo genome editing for MPS I and MPS II and also AAV cDNA gene therapy for Fabry disease. Our strong balance sheet ensures that we'll have the resources to advance these programs to registration studies and potentially to pursue other indications using the albumin locus genome editing approach.

Second, CNS indications using our zinc finger protein transcription factor technology. This is an area where we can leverage the significant know-how from our experience in the next-generation AAV design, CNS delivery and ZFP transcription factor design and authorization, as we've done in Huntington's disease with Shire and similarly with C9 oxalate ALS disease with Pfizer. In addition, we intend to invest and develop these types of gene regulation products.

And finally, ex vivo cell therapy immunology indications, where we're exploring the potential of genome editing to significantly improve the lives of patients living with severe immunology diseases. This is an area where we can leverage the significant know-how from our past experience in gene-edited cell therapy. We believe, with our ex vivo editing capabilities and our experience handling T cells, we have a competitive advantage in this emerging and promising field. And that time is now for Sangamo to invest in this area.

Another near-term investment would be in our employees. Strong execution requires recruitment of top talent and building a world-class biopharmaceutical organization. Attracting talent is one reason we're moving to our headquarters at the end of this year to Brisbane in the heart of biotech cluster in South San Francisco.

In addition, we'll increase our investment in manufacturing and infrastructure to include cell therapy as well as AAV vector production. We expect first clinical-ready production from our own GMP facility in 2020. Although we plan to increase investment for Sangamo's proprietary programs and capabilities, we will continue to collaborate, especially in therapeutics areas that are highly competitive or that require special disease area expertise or to significant investment to develop and commercialize ourselves.

Over the past year, this collaboration strategy has led to meaningful partnership with Pfizer for gene therapy for hemophilia A, a highly competitive market; and with Kite, Gilead for oncology, where specialized expertise and resources are required to become competitive. We will also consider collaborations when partners come to us with ideas for new uses of our technology. We believe our strong balance sheet affords us more choices in when and how we partner.

With our planned investment for 2018, our operating expense guideline is between $140 million and $250 million (sic) [$150 million], with an anticipated 2018 year-end cash balance of $485 million. Assuming no other strategic investments, our cash balance is expected to last the next 5 years.

And with that, I'll now turn the call over to Ed Conner for review of our therapeutic development strategy.

Thank you, Kathy, and good morning, everyone. Before I dive into the clinical update, I'd like to reiterate our strategy for data readout in advance or expected initial efficacy data disclosure in late summer.

As we've said before, we plan to release data from each program, and we believe it has had time to mature and is clinically meaningful and reliable. The first 2 programs for readout will be our SB-525 hemophilia A gene therapy and our SB-913 MPS II genome editing programs. We expect to present top line safety and efficacy data for the first 2 dose cohorts from each program in the late summer.

Turning to Slide 19. The SB-525 hemophilia A program, which is being developed in collaboration with Pfizer, is based on our AAV cDNA gene therapy approach to deliver a functional copy of the Factor VIII gene to the nucleus of liver cells. The goal for SB-525 is to produce stable, consistent and therapeutic levels of Factor VIII protein from the liver and into the bloodstream. The literature and experts in the field have stated the factor levels above 12% of normal are sufficient to prevent bleeding. Our target for factor levels in the blood are to be well above this 12% threshold, but less than 150% of normal, as levels above 150% of normal may present a risk of thrombosis. We currently have 8 sites open for this Phase I/II trial in 4 patients dose in the first 2 dose cohorts of the study. We anticipate dosing the next patient soon. Again, we expect to release top line efficacy data from the SB-525 program in late summer.

Next, turning to Slide 21. Our SB-913 MPS II in vivo genome editing program uses our zinc finger nuclease technology to target a precise sequence in the liver cells' DNA just downstream of the albumin promoter to allow for insertion of the gene encoding for the metabolic enzyme, IDS. We currently have 5 sites open for the SB-913 Phase I-II CHAMPIONS Study with 4 patients treated across the first 2 cohorts. As a reminder, the primary and secondary endpoints of the study include evaluating safety of the product, IDS enzyme activity in the blood as well as urine GAG levels. The level of stable and consistent plasma IDS expression needed to provide therapeutic benefit may be as little as 2% of normal according to MPS experts. At current standard-of-care enzyme replacement therapy or ERT is unable to achieve even this enzyme level. We expect to release top line efficacy data from the SB-913 MPS II study in late summer.

Next I'd like to turn to SB-318 in vivo genome editing program for MPS I also summarized on Slide 22. I have an important update to the study protocol for the SB-318 MPS I Phase I-II trial. After reviewing the safety data from the first cohort of our MPS II trial, the FDA agreed with our plan to skip the first dose for the MPS I study and enroll subject directly into the second dose cohorts. We're very pleased with this change. And with the strong sense of responsibility for our patients, we feel that this is the right path forward for the program. I'd like to reiterate that this decision was based exclusively on the Safety Monitoring Committee's review of early safety data from MPS II and has the potential to allow us to accelerate timelines for the SB-318 study.

We currently have 6 sites open for the SB-318 Phase I-II clinical study, 4 patients in screening who have passed initial lab assessments. We have additional patients advancing through the screening process, and I expect to enroll the first patient in this program soon.

I want to take a moment to provide additional context on how we're thinking about the MPS I and MPS II clinical trials for our in vivo genome editing programs. These trials will provide a benchmark for AAV delivery capabilities of zinc fingers. As Sandy has mentioned before, we know that our zinc finger nuclease technology can effectively edit DNA. We've tested ZFN's precision, efficiency and specificity in various environments, conditions and cell types. The ZFNs have effectively edited mammalian animal cells in the test tube, isolated human liver cells in the lab, liver cells in nonhuman primate animal studies for the Factor IX program and both T cells and stem cells at clinical scale ex vivo.

The question is not whether the zinc fingers can edit DNA, but whether we can deliver the right concentration of zinc fingers and therapeutic gene to liver cells in vivo. We're confident that if we get a high enough concentration of all 3 components into the cell, then efficient editing will take place.

As we discussed on prior calls, our goal for our genome editing programs is to move toward enrollment of pediatric patients as soon as possible, as the pediatric population is where we believe medical need is greatest for our therapies. We will include adolescents and children in the current Phase I-II studies once we've collected appropriate safety data in adults. We've also submitted CTAs to initiate pediatric studies for MPS I and MPS II in the U.K. and are hopeful we can expand enrollment to the U.K. by the end of 2018.

Turning now to our SB-FIX program for hemophilia B, our third albumin locus in vivo genome editing programs, which is summarized on Slide 23. In this case, we insert a new Factor IX gene, the code for cloning Factor IX protein, with the goal of having liver cells produce a steady and consistent level of clotting protein for the lifetime of the patient. We've previously discussed the enrollment challenges this program has faced in the U.S. We currently have 4 sites open in the U.S. and continue to screen for eligible patients.

Earlier this year, the U.K. regulatory authorities granted our CTA for enrollment of both adolescent -- of both adult and adolescent subjects, ages 12 to 17, into the ongoing Phase I-II study in the U.K. The enrollment of adolescents may begin once preliminary safety and efficacy of SB-FIX has been demonstrated in adults. We're very excited to begin expanding enrollment of this study to the U.K. And Duncan McKay, our VP and General Manager of Sangamo Europe, is already working to activate the sites in the U.K. and to enroll patients there by year-end.

Moving on to ST-400 cell therapy for transfusion-dependent beta-thalassemia on Slide 25, which is our fifth active clinical development program. We are developing ST-400 along with BIVV-003, which uses a similar approach for sickle cell disease, in collaboration with Bioverativ, a Sanofi company. I am pleased to report the first site for the ST-400 Phase I-II clinical study has been initiated. A second site will open very soon. And we remain on track to enroll the first patient in this study in the first half of 2018. We plan to enroll a total of 6 patients, all to be treated with the same dose. And the protocol allows for subsequent patients to undergo apheresis, while prior patients are enrolled and cell product has been manufactured. This allows for the shortest possible enrollment time between patients.

As you may know, ST-400 uses ZFN-mediated differentiated gene editing approach for treating beta-thalassemia, mimicking naturally occurring genetic variance in the human body to boost fetal hemoglobin expression. The manufacturing of ST-400 involves ex vivo nonviral mRNA delivery of ZFNs, a potential strategic advantage of a randomly integrating lentiviral-based approach is currently being developed. I look forward to providing additional updates on the beta-thalassemia program on our second quarter call.

We were also pleased recently to have been awarded an $8 million grant by CIRM, the California Institute for Regenerative Medicine, for the development of ST-400. The final program I'll mention is the ST-920, our AAV cDNA gene therapy for Fabry disease. We are completing preclinical work on that program and expect to submit an IND this year.

As you can see, 2018 and 2019 have the potential to be transformative years for clinical development at Sangamo, as we expect to have clinical data readouts from 7 clinical trials across our in vivo genome editing, ex vivo genome editing and gene therapy approaches. I'm very excited for the next 18 months and look forward to providing updates on our progress on future calls.

I'll now turn the call over to Michael Holmes, our Chief Technology Officer. Mike?

Thank you, Ed, and good morning. Next week, we will attend ASGCT, the Annual Meeting of the American Society of Cell & Gene (sic) [Gene & Cell] Therapy.

Each year at this meeting, our scientists present selections of recent research and technology development. This year, we have 3 podium talks and 4 poster presentations.

Several of our technology presentations showcase recent enhancements to our ZFN genome editing platform and build upon the precision, efficiency and specificity framework for evaluating therapeutic genome editing technologies.

As a reminder, precision is the ability to target a specific, clinically relevant nucleotide or a sequence down to a single base pair. The ZFNs can be engineered to target any nucleotide in the genome. Efficiency describes the level of modification achieved at the desired target site. With ZFNs, we can now routinely hit greater than 90% efficiency, even as high as 99.5% efficiency.

Specificity is a term used to describe the degree of off-target editing. We understand how off-target cleavage occurs via nonspecific finding between the ZFN and the DNA backbone. We are able to engineer away these elements from the ZFN, and the result is that off-target cleavage falls to levels that are undetectable by state-of-the-art assays. I encourage anyone interested in therapeutic genome editing to continue to ask Sangamo and others in the field about all 3 of these parameters.

Next week at ASGCT, Russ DeKelver will present initial results of this research -- of his research into rational enhancements to increase ZFN in vivo activity levels. Russ shows that with changes to the AAV ZFN expression construct backbone and through the DNA-binding a nucleus domain ZFN coding sequences, we can achieve 10- to 30-fold increase in activity levels. We believe these are impressive results -- impressive improvements that may provide foundation for next-generation in vivo genome editing. Ed Rebar's presentation described methods for improving specificity and overall activity of ZFNs and ZFP-TF. He described the identification of highly conserved, nonspecific phosphate contacts between the zinc finger domain and the DNA backbone. Substituting these contacts and varying the number of zinc fingers bearing this change provides an effective means for tuning total activity and on-target preference. With this modification and others Ed describes, Sangamo scientists have been able to generate ZFNs that target precise nucleotides with very high efficiency in undetectable off-target modification.

Sangamo scientist, Anthony Conway, will present some of our recent work developing nonviral delivery methods for tissues beyond the liver. Delivery is one of the biggest obstacles in developing in vivo gene therapies to tissues outside the liver. And investing in delivery is critical to our vision to one day edit any gene and any tissue. Anthony describes how we evaluated intravenous lipid nanoparticle delivery of a payload of mRNA encoding for ZFNs targeted to the male CFTR gene. In our initial investigation of this method of delivery for lung tissue, we achieved greater than 10% INDELs in lung epithelial cells following a single dose, with only minimal editing observed in both liver tissue.

At ASGCT, Marshal Houston will present abstracts for 2 approaches to treat Fabry disease, which we expect will be our next proprietary inherited metabolic disorders clinical program, with an anticipated IND filing later this year. Brian Ziegler will present an overview of recent work developing ZFP-TF in viral CNS delivery methods to knock down expression of tau, a key protein implicated in the development of Alzheimer's disease and other dementias. Nonhuman primate studies for this program are ongoing, and we expect to present results from that research once the experiments are completed.

Finally, Sumiti Jain will present recent advancements in our ex vivo editing capabilities. Sangamo scientists have been able to achieve highly efficient multiplex editing of T cells using ZFN. And this capability proved extremely valuable to Sangamo earlier this year, as we're able to partner this technology with Kite-Gilead for their use in the development of new autologous and allogeneic cell therapies for oncologies.

I'll now turn the call over to Sandy for any closing remarks. Sandy?

Thank you, Mike. Sangamo is at an inflection point, catalyzed by exciting upcoming clinical trial readouts from 7 different programs using a diverse range of technological approaches. We're rapidly advancing additional research programs for our proprietary pipeline as well as in collaboration with partners.

We're making enormous progress industrializing our ZFN platform, so our best technology is readily available to internal and external researchers. And we're successfully recruiting new talent throughout the company to ensure that Sangamo is geared financially and operationally to continue to lead the field of genomic therapeutic development.

We'll now turn to you for your questions. Operator?

(Operator Instructions) Our first question comes from Ritu Baral with Cowen.

Sandy, can you talk to the follow-up period for the hemophilia A patients and the MPS II patients that we will have upon data release? And do you expect stabilization of expression within this period?

It's an important question. Let me hand over to Ed, our CMO, to try and address this.

Sure. So it will be based on when the -- it'll be based on when the patients are enrolled in the respective studies that you mentioned. And as we mentioned during the call, we want to ensure that the data has had time to mature and that we're able to report on meaningful and reliable data.

But just trying to be -- maybe being a bit more philosophical here. I've spoken with many of you about the danger of coming out with data too early when it's -- when the levels are still settling. We've also reflected together on the fact that between the other companies that have shown data in hemophilia A, there aren't that many data points for us all to know how long it takes for this to settle and how long the data will take to evolve. And so this is a growing field. We believe that by waiting until late summer, we have the best chance of having data that is meaningful and will give you the best chance to understand the quality of our medicine.

Fair enough. And just a quick follow-up. Can you give us very sort of high-level MPS II safety from Cohort 1? I mean, it sounds very positive. Does it generally resemble the first patient that you've seen? Any other considerations there?

Yes. So we presented data at the world meeting, which was back in February, that demonstrated the first dose cohort was well tolerated.

And the other?

Yes, it was -- sorry.

Do they generally -- the additional patients, do they -- can we assume that they generally resemble that presentation in the first patient -- from the first patient?

Yes -- I mean -- yes. So the patients in the second cohort -- again, the study continues, and we continue to enroll patients. So we haven't commented on the safety except, as I said, for the first dose cohort for the MPS II study. But as the study continues, you can make your assumptions based on that.

Our next question comes from Gena Wang with Barclays.

This is actually Xiaobin dialing in for Gena. Maybe first a quick one on hemophilia A. So you mentioned that you're about to enroll the next patient very soon. So would the patient be treated by the first dose? So what's the rationale sort of to continue to dose escalate? And can you also share a little bit more about your target profile based on existing data?

So we've said we will continue to dose escalate. The -- we will wait until the data reads out to give us appropriate impression of the therapeutic dose. And the study continues.

Got it. Maybe also just a couple of quick financial questions maybe for Kathy. It's -- so for the Kite upfront milestone, how would you book it? Would you amortize it? And what would be the time period that we should use? And also can you help us bridge your current cash provision and your OpEx guidance to your year-end cash provision? It seemed that if you just minus the OpEx for the remaining of the year, so you get to the $485 million cash position. But how should we think about the revenue and CapEx?

Okay. So let me address the Kite-Gilead upfront for -- as you know, the HSR did not clear until April, which is in Q2. And we are going through it right now, analyzing the impact of the ASC 606 accounting guidance on to this upfront revenue, which -- basically in prior periods, prior accounting guidance, we took a very straight-line approach of dividing that -- amortizing that revenue over a straight-line method. But going forward, we have to analyze the performance period and how much is the revenue we can account for the performance that has been delivered against that obligation. So it will be something that we have to analyze in the upcoming quarters, and we will provide more information at that time. So did I answer your question? Did I address your question on that revenues?

Yes. Yes. About the guidance?

Yes. On the second point regarding operating expense and cash guidance, you're right that it's roughly in line with how we think about -- how -- what we're going to recognize as operating expense and how that ties back to our cash guidance. It's roughly in line. But remember, as we are building a huge facility in Brisbane, the cash impact of that would be something that we have to monitor towards the end of this year.

Our next question comes from Maury Raycroft with Jefferies.

To start, sort of similar line question as what Xiaobin just asked (inaudible). But I'm wondering for MPS II, so you've dosed the initial patients with 5e12. And then you've got the next cohort with 1e13. And now you're looking to dose 2 more patients at 5e13? Or do you plan on dosing more patients at 1e13?

So -- this is Ed. We aren't commenting on dose expansion or dose escalation for the MPS II or Factor VIII studies.

Okay. Okay. And then for MPS II, if you can just remind me what the protocol is for steroid use and if you can comment on tapering for the 4 patients treated so far. And if it's possible for you to see -- if possible, if you can comment on any benefits that you're seeing on efficacy that relates to the tapering?

So not commenting on efficacy. As we talked about, we'll release efficacy and safety data late summer. With regards to the prednisone dose, it's a 20-week steroid taper, starts at 60 milligrams and fairly rapidly tapers down to a relatively low level.

Got it. Okay. And just also for when to expect data, will that be -- should we expect it at a medical meeting? Or do you plan on doing a press release around MPS II and then hemophilia A?

Mario, it's McDavid. We have got our eyes on a few different venues for the actual presentation at a medical congress in the late summer for both programs, and we'll likely top line release that in advance of that.

(Operator Instructions) Our next question comes from Jim Birchenough with Wells Fargo.

Just want to understand, in the slide deck, it speaks to midyear clock wind data. And now we're talking about late summer. So just trying to understand what's happened recently and whether there has been an efficacy assessment and you're electing to move forward? Or whether you're waiting for data to get more mature or you expect a better yield from an efficacy assessment?

Jim, it's the latter. And it's a fascinating discussion with the lawyers about what's the middle of the year and what's summer and what's the late summer. And so we're aiming for late summer. Nothing has changed. There is no delay in the programs as we've described them. It was just -- when is the middle of the year and when is the summer.

Got it. Okay. And then just a lot of time appropriately spent on delivery and optimizing delivery. Is there a provision in the protocol to look earlier for evidence of transfection? And have you looked -- are there any biopsies to look at that question to assess delivery as well as other aspects of the geno editing itself? And do we have any early evidence that any of this is getting toward an ECS too?

So you can imagine liver biopsy as a significant thing that we can only do rarely in patients. And so we will look first for efficacy by enzyme level. Deliver biopsy comes towards the end of the patient's intensive study, so -- rather than it being an early indicator.

Yes, and just to add to that, with the enzyme levels. We're very fortunate, because the -- we're very fortunate from an assessment standpoint, because the enzyme replacement therapy levels are -- basically, if the patient's native production prior to their next dose, the half-life of enzyme replacement therapy is quite short, hours. And so even 24 to 48 hours afterwards, the only enzymes the patients are producing is what they would have produced on their own. So this allows us then to measure enzyme levels just prior to their next dose of receiving ERT. So we then have a strong ability to detect changes.

And Jim, I want to just reemphasize something that Ed said in his talk. I know you understand. We've done this experiment in vitro in most monkey and human. We've done it in vivo in mouse and monkey. Each time the zinc fingers -- if you enough concentration in the cell, we added and the gene gets incorporated and transcribed. And so really what we're testing here is enough -- there's enough of our AAV6, take them to liver in the human in vivo experiment for that production. It isn't as much a test of the editing, it's a test of the delivery.

And maybe just one final question if you'll allow me. Obviously, a lot of focus on Huntington's gene silencing recently. You've got a program with Shire. Any update there? And maybe harder to answer, but any implication of the Takeda-Shire deal on that Huntington program? Is there any provision where it might return to you?

So having come from Takeda before joining Sangamo, it's fascinating how complicated the world is. I know neuroscience has always been a big thing for Takeda. So I'm sure it's only good news. We hear from Shire that the trial -- the trial -- I misspoke there, the program progresses.

I show no further questions in queue. So I'd like to turn the conference back over for closing remarks.

Thank you so much for joining us this morning. Have a good day.

Thank you. Ladies and gentleman, that concludes today's conference. Thank you very much for your participation. You may all disconnect. Have a wonderful day.