Good day and thank you for standing by. Welcome to the Sangamo First Quarter 2021 Teleconference Call. At this time, all participants are in a listen only mode. After the speakers' presentation, there will be a question and answer Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Erin Feingold, Head of Corporate Communications.
Please go ahead.
Good afternoon, and thank you for joining us today. With me this afternoon on this Call are several members of the Sangamo executive leadership team, including Sandy McRae, Chief Executive Officer Mark McClung, Chief Business Officer Jason Fontenot, Chief Scientific Officer Rob Schott, Head of Development and Bettina Cockcroft, Chief Medical Officer. Slides from our corporate presentation can be found at our website sangamo.com under the Investors and Media section on the Events and Presentations page. This call includes forward looking statements regarding Sangamo's current expectations. These statements include, but are not limited to, statements relating to advancing our programs, plans and timelines for enrolling and conducting clinical trials, presenting clinical data and opening new manufacturing facilities, our 2021 financial guidance, our expectations regarding our financial performance and sufficiency of our cash resources and other statements that are not historical Actual results may differ materially from what we discuss today.
These statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC, specifically our annual report on Form 10 ks for the Fiscal Year Ended December 31, 2020. The forward looking statements dated today are made as of this date, and we undertake no duty to Reconciliation of this measure to our GAAP operating expenses can be found in today's press release, which is available on our website. Now I'd like to turn the call over to our CEO, Sandy McCriss.
Thank you, Aaron, and good afternoon to everyone on the call. This quarter, we have continued our focus on advancing our lead programs through clinical execution, Regulatory interactions and collaboration with our partners and investigators. This morning, Pfizer's CEO announced on their earnings call The progress continues with our partnered hemophilia A gene therapy product candidate, highlighting that the lead in study For Pfizer's registrational Phase 3aFine clinical trial is now fully enrolled, which could lead to a pivotal readout as early as 2020 With Sanofi, we announced that the EMA has granted orphan designation to BIPB003, now known as SAR-four hundred and forty five thousand one hundred and thirty six, our cell therapy product candidate for the treatment of sickle cell disease. The orphan designation was based on preliminary clinical observations submitted to the agency. We and Sanofi also received Fast designation from the FDA for this program.
We are pleased with this progress and expect to present initial data at a medical meeting by the end of 2021. In March, we initiated our SEPAST clinical study evaluating TX200, our wholly owned CAR Treg cell therapy product candidate in renal transplant rejection,
which we believe will be
the 1st in human clinical study of a CAR Treg therapy. We are pleased to open clinical sites sooner than expected and hope to have a first patient move by the end of the year. We see this study as the first step in our R and D journey towards allogeneic CAR T right therapies for autoimmune diseases, which we hope to develop as wholly owned product candidates in our pipeline. Our research engine has been highly productive this quarter. We continue to focus on our innovative areas, including CAR Tregs for autoimmune diseases and transcriptional regulation with zinc finger proteins for neurological diseases.
The versatility of our zinc finger technology to address challenging diseases of the central nervous system was highlighted this quarter with data publications and presentations from our tau and alpha synuclein programs. Before I turn the call over to the team, I'd like to take a moment to acknowledge that this quarter marked 1 year of working in the challenging conditions of the pandemic. I continue to be so impressed by the Sangamo team's resilience and determination as our lab employees have adapted to distancing procedures and as our remote colleagues tune into Zoom calls from kitchens and bedrooms. I'm proud of the strong team we have in place to execute on the catalyst risk With that, I'll turn the call over to Rob Schott, our Head of Development, who will provide additional details on our clinical accomplishments. Rob?
Good afternoon.
Our development organization remains focused And we are pleased with this quarter's progress. As Sandy mentioned, enrollment in Pfizer's lead study in the Phase 3 APHINE trial Evaluating our hemophilia A product candidate is complete. The purpose of this study is to collect a minimum of 6 months of prospective efficacy data of current Factor VIII prophylaxis replacement therapy in patients with hemophilia A to establish baseline characteristics Prior to dosing with goritotukine filoparvavec in the APHINE trial, Pfizer expects a pivotal data readout as early as 2022 as well as a 2 year update from the Phase III Alta study in the Q4 of this year. Regarding our Fabry program, We continue to advance the Phase III STAR study and we have recently enrolled the 4th patient. We plan to present initial data from this study in the Q4 of this year.
In March, the EMA granted orphan designation to BIVV003, now known as SAR 445136, our sickle cell disease product candidate partnered with Sanofi. This decision was based in part on early data from 3 treated patients that had 52 weeks, 13 weeks and 29 days of follow-up respectively. In a recently published minutes, the EMA's Committee for Orphan Medicinal Products determined that preliminary clinical observations as well as the potential of long term effects that may obviate the need for frequent treatment suggest a clinically relevant advantage versus hydroxyurea. Last month Sanofi announced that this program received fast track designation from the FDA. We find the progress on this program encouraging.
We and Sanofi expect to present the initial data from the PRECISION-one study at a medical meeting by the end of this year, which will reflect a more mature and more portfolio review, KITE made a decision not to submit the KITE-thirty seven IND at this time. We are working closely with KITE to determine the path forward for KITE-thirty seven. Our collaboration remains focused on developing best in class oncology engineered cell therapies. Together, we believe that KITE's oncology expertise and development experience paired with Sangamo's zinc finger platform and cell engineering capabilities positions the collaboration Well within the space. Lastly, we are very pleased to have initiated our Phase III steadfast study earlier than expected.
This study is evaluating TX200, our autologous HLA A2 CAR Treg cell therapy product candidate in patients receiving and HLA A2 mismatched kidney from a living donor. Patient recruitment is now open at clinical sites in Belgium and the Netherlands. The primary objective is to assess the safety and tolerability of TX200. Secondary objectives include the incidence of biopsy confirmed acute Graft rejection, incidence of chronic graft rejection and localization of TX200 CAR Treg cells in the transplanted kidney. We also plan to evaluate the ability to reduce systemic immunosuppressive therapy, which can be associated with side effects such as an increased risk We plan to enroll up to 15 patients in the group receiving TX200 and up to 6 patients in a control group.
We plan to evaluate 3 doses with 3 patients in each dose cohort with the option for an expansion cohort with up to 6 additional patients. The study will be monitored by an independent safety monitoring committee, which will give its go ahead before moving to the next dose cohort. Patients in the TX200 group will undergo a leukapheresis to collect white blood cells Prior to their transplant surgery, we will isolate a subset of Treg cells and modify them to add a chimeric antigen receptor or CAR to allow specific recognition of the HLA A2 protein present on the cells of the donated kidney. After transplant surgery and a several months recovery period, the patient will receive their one time individualized PX200 infusion. We expect to enroll the 1st patient in this study by the end of this year and expect that dosing will occur several months thereafter.
We believe that by directing the Treg cells to the transplanted organ by way of the chimeric antigen receptor, TX200 has the potential to mitigate graft rejection and reduce the need for systemic immunosuppression. We see this study as offering an opportunity to demonstrate important proof of concept CAR Treg Biology in Humans, as well as to better understand CAR Treg Process Development. I will now turn the call over to our Chief Scientific Officer, Jason Fontana, for additional details on these research programs. Jason?
Thank you, Rob, and good afternoon, everyone. Today, I'm delighted to give you an overview of a few of our exciting research programs. We can engineer our zinc finger proteins or ZFP to precisely target essentially any DNA sequence in the genome. We have invented methods to tune VFP interactions with DNA to optimize specificity and precision, and we have developed methods to pair this targeting capability with a range of functional domains. These functional domains include transcriptional activators and repressors that can modulate gene expression without altering the genetic code, nucleases that can edit DNA And we are advancing ZFP targeted base editors and recombinations.
We can deploy these tools in vivo or ex vivo to create powerful therapies with the potential to treat significant diseases. As Sandy touched on, we are using our zinc finger protein transcription factors to develop promising therapies for diseases of the central nervous system and had some exciting preclinical data highlights this quarter. First, Data from our tau program in collaboration with Biogen published in Science Advances showed the tau targeted zinc finger transcriptional delivered via single AAV administration, selectively reduced tau messenger RNA and protein by 50% to 80% out to 11 months. This without detectable off target effect. 2nd, data from our Alpha's Nuclein program, also in collaboration with Biogen, presented at the Alzheimer's and Parkinson's Disease Conference, showed that alpha synuclein targeted zinc finger transcriptional repressor could significantly repress human alpha synuclein and were well tolerated in vivo.
And finally, Data from our alpha synuclein program as well as our C9orf72 program, which was exclusively licensed to Pfizer, have been selected for presentation at the American Society of Gene Cell Therapy Annual Meeting next week. We look forward to keeping you updated on these and other pre As Rob mentioned, our steadfast CAR Treg clinical study opens for enrollment this quarter. I want to provide some additional color on our research strategy with regards to our CAR Treg portfolio. Regulatory T cells called Tregs have potent natural immunosuppressive properties and have the potential to be therapeutically harnessed to treat diseases characterized by unwanted or Unmodified polyclonal Tregs, a mix of Tregs, which overall do not target a particular antigen, have been studied in autoimmune diseases as have been shown to be safe. We are developing antigen targeted CAR Treg I believe that our approach may overcome the limitations of polyclonal Treg by directing the Tregs to the relevant disease tissue where they will be activated and expanded upon CAR binding with the target antigen.
The antigens targeted by our CAR Treg can be linked to the disease ideology or simply be localized in the disease tissue. For example, in our multiple sclerosis program, we are Programming CAR Tregs to target myelonolgabendricyte glycoprotein or MOG. MOG is expressed specifically in the central nervous system and Similarly to a GPS, we will aim to drive our MOG specific CAR T regs to expand at this site of inflammation, where they could suppress the pathogenic immune reaction responsible for MF. In our inflammatory bowel disease or IBD program, We are targeting the receptor for the interleukin IL-twenty three or IL-twenty 3R, which is known to be expressed at We're using our zinc finger genome engineering platform to develop allogeneic Tregs, edited Tregs from healthy donors ex vivo to reduce off the shelf CAR Treg cell therapy. We are also investigating the potential use of induced pluripotent stem cells or iPSCs as a renewable source of large quantities of Treg cell.
We are making progress on these programs, working first to developing efficient and proprietary CAR structures and then on obtaining proof of concept preclinical data, both in vitro and in vivo. We look forward to presenting our preclinical data in due course. I will now turn the call over to Mark for an overview of the financial results. Mark?
Thank you, Jason, and good afternoon, everyone. As Aaron had mentioned previously, our financial results for this quarter are available in the press release issued this afternoon, which can be found on our website. This quarter, we invested in the advancement of our clinical programs, moving forward our preclinical research pipeline and continuing to build our in house manufacturing capabilities. We ended the quarter with approximately $630,000,000 in cash, cash equivalents and marketable securities. We believe that our balance sheet remains strong and will allow us to reach several important R and D milestones, including the potential submission of the BLA for our hemophilia A product candidate.
Turning to 2021 full year guidance, we would like to reiterate the guidance we provided in our prior call. We continue to expect non GAAP operating expenses, which exclude estimated non cash stock based compensation expense of approximately $30,000,000 be in the range of approximately $255,000,000 to $275,000,000 for the year. I'll now turn it back to Sandy for closing remarks.
Thank you, Mark. I'd like to conclude by saying that we're pleased with the progress this quarter across our development and research organizations and continue to believe we have the balance sheet strength to execute on our R and D milestones. Our manufacturing team continues to advance our in house Cell therapy manufacturing facilities, which we expect to be operational by the end of the year. We look forward to key milestones and catalysts by year end, including initial data readouts on sickle cell and Fabry, as well as a 2 year update in hemophilia A. Operator, please open the line for questions.
Thank you. Please stand by while we compile the Q and A roster. Our first question comes from the line of Luca Iffi from RBC. Your line is now open. Perfect.
Thanks for taking the question. This is Lisa on for Luca from RBC. Just wanted to ask, so we saw yesterday that AbraBio will no longer be able to pursue and accelerate approval pathway for Fabry disease that they may need to run a Phase 3 trial head to head versus standard of care Fabryne. So I was just wondering what your reaction was to that news? And how does that influence your development strategy going forward for your gene therapy product?
Thank you.
Thank you for your question. Each company has There are individual discussion with the agency. Bettina, you've been working in Fabry for some time now. What was your take on that announcement?
Yes. Sure, Sandy. Thank you. Well, first of all, what we are doing is we're currently I'm pressing full quarter ahead on enrolling the Fabry study, that Phase III STAR study. And as you've heard Rob mention, We have dosed 3 patients and have enrolled a 4th patient, and we hope to enroll and talk to those soon.
We are looking forward to sharing initial data readout in Q4. Now our study design includes collecting biomarker data and as we've mentioned in the past as well, We will conduct kidney biopsies at the appropriate time. The study is currently on effect just by the recent regulatory updates that you're referencing. And for sure, we are engaging with the agency. And at this point, as you'll appreciate, it's too early to share an update on that front.
Thank you, Bettina.
Great. Thanks for taking the question. Thank you. Our next question comes from the line of Maury Raycroft from Jefferies. Your line is now open.
Hi.
This is On for Maria Raycroft. For TX200, we noticed the trial initiated a bit earlier compared to the 4Q press release. What work needs to be done before the patient enrollment second half of twenty twenty one. Thanks.
Thank you for your question. Yes, we were pleased with the clinical operations group managing to initiate sites. I think they've done And now it's simply a matter of moving forward and enrolling patients and preparing for the dosing of the patient. This is the first time that we have dosed a patient with CAR Treg. And so we're going to take care, be prudent, make sure we have the right patient and the right manufacturing process to be able to drive forward and do this well and hopefully show that CAR Treg's potential is matches everyone's excitement around this area to allow us to move into many autoimmune conditions.
Thank you. Our next question comes from the line of Geoff Meacham from Bank of America. Your line is now open.
Hey, guys. It's Aspen on for Jeff. Thanks for taking the questions. Just two quick ones from us. First of all, Sandy, I'd love to hear your thoughts on the current regulatory environment, specifically with respect to CEBR.
Any sort of reduced communication or are you feeling any sort of shift in mentality from the agency in any respect? And then secondly, just looking for a little bit more clarity on the on Kite's decision not to submit the IND. Just wanted to see if you had any additional feedback you can share with us. Thanks.
So let me take the more philosophical one and then I'll pass it on to Mark for the business discussion around current. I saw this week that Peter Marks was given an award For his service to Advancing Medicines and it feels totally appropriate. We have a great relationship with CEVA. They Are doing a difficult job and are flexible and thoughtful. I often get asked Has the regulatory environment got harder or be asking more?
And I would reflect it the other way around. The 7 gene therapy was this is this wonderful concept that we all are so excited by. And now what we're meeting is the reality of what it takes to have Amexin approved. It's about ensuring your manufacturing It's good. Your self process is good.
Your science is good. The clinical trial is good. And it's not surprising that the Some of the excitement is now meeting reality. We take these stages extremely seriously at Sangamo. We invest greatly in CMC Regulatory Interactions and Manufacturing and are comfortable Confident that the agency hasn't changed its opinion.
But I'll pass on to Mark now for Kite Gilead. Mark, do
you want to talk about that?
Sure. I mean, as Rob reiterated, Kite made the decision not to submit the 0 37 IND at this time, and the team is going to look a little bit closer to understand the potential path forward. This has been made in the context of the emerging early data from 2 competitors that were ahead of the 37 program, But also in the context of the data that Kite has on hand with the start up product, which the focus is really to drive something which would be a best in class alternative and would allow for an expansion of utilization of these products. And so The goal is to continue to apply tight expertise in the development of oncology compared with our zinc finger platform and cell engineering capabilities to really look for opportunities to develop and advance best in class
Thank you. Our next question comes from the line of Yanan Zhu from Wells Fargo Securities. Your line is now open.
Hi, thanks for taking my questions.
I have
a question regarding CX200. I see that it's enrolling in Belgium and Netherlands. Wondering, is there any difference in terms of the Immunosuppression that is used for the renal transplant procedure, any difference between Europe and the U. S? And if there is some difference, would you also plan to open an IND in the U.
S. To have a more relevant treatment procedure for the U. S. Application? Thanks.
Thank you for your question. That's an interesting question because renal transplant and how you treat it is differs a little from country to country. Bettina, would
you feel comfortable to talk about that?
Yes, for sure. I mean, Sandy, you said that there are differences from country to country In addressing immunosuppression in renal transplant, we our study, as we've mentioned, has recently initiated and we are enrolling in these first two countries. You've mentioned the Netherlands and Belgium. We do intend to open the study also in other countries, especially in other European countries. So this is something that we will hopefully be able to update you in the future with.
I might also add, this is Rob Schott, that there's often institution to institution differences in immunosuppressive therapies And you can even find differences within institutions between investigators. And we rely on The investigator judgment with respect to immunosuppression and therapy consequent or following the TX200 therapy.
Got it. That's very helpful. And then maybe a follow-up on The C9orf72 program, could you talk about the potential advantages for using the linked finger protein transcription factor versus using gene therapy that delivers SHRNA, for example, to knock down
Sure. We'd be happy to. Jason, can you help us with that one?
Sure, Sandy. I think the key difference is really About the platform technology, about our platform technology and our ability to fine tune the interaction of our zinc finger proteins With the designated target. So we have very fine control over that and we have the ability to identify And then single protein can accomplish what we set out to accomplish with the therapy and not have any off target. And I think that there's A major difference between our ability to do that with zinc finger proteins and competitors.
And then beyond that from a clinical point of view, the army therapies seem to need to be given frequently. We would hope that episomal expression of a transcription factor will give a long lasting effect. It seems to do it in animals. Until we get into humans, we won't know for sure. But the promise this gives to patients of our once and done Therapy is really important.
These are dreadful diseases and if we can address them with our transcription factor, we will Fulfill our mission and promise.
Great. Thanks for the color.
Thank you. Our next question comes from the line of Gena Wang from Barclays. Your line is now open.
Hi, this is Swapnil on for Gena. Thanks for taking our questions. So I had a Fabry question. Since Looks like GB3 reduction in kidney biopsies could serve as a surrogate endpoint. Is it safe to assume Like you're predominantly focused on recruiting patients with kidney defects.
And Do you think that FDA would require longer term follow-up to monitor EGFR to grant full approval based on the Fabrizyme update?
Thank you for your question. The agency is doing its very best in my mind To make the pathway forward for Fabry clear and tractable, What they have said is GV3 reduction in the kidney with the commitment to have a long term EGFR Benefit is a pathway to approval. And therefore, I think that understanding the effect on the kidney is important. Now, We are recruiting patients that are on enzyme replacement therapy, are naive and are pseudo naive in the current study. We are looking to show a biochemical effect and then we will move towards doing kidney biopsies.
So I think simply the patient population is wide ranging from patients that already had renal damage to those that are Undamaged. And what my reading of the literature tells me is that this is an important Consequence to the patients and the patients show renal damage from very early on. So in amongst that population that we're already But let's wait. Let's see the results at the end of the year and let's work out a sensible path forward.
Got it. Thanks for taking my questions.
Thank you. Our next question comes from the line of Ritu Baral from Cowen. Your line is now open.
Good afternoon, guys. Thanks for taking the questions. It's actually me. I wanted to ask you about the rationale for picking HLA A2. On Slide 11 of your corporate deck, You note that 21% to 26% of the transplanted of renally transplanted organs are HLA2, A2 mismatched.
First of all, I wanted to make sure that that 21% to 26% was renal was kidneys and not just organs in general. And second, in your comments today between MS and IBD, It seems like you were implying that you had sort of multiple targets per program picks, auxiliary targets. I was wondering If you also were thinking that had an auxiliary target for renal transplant and what portion of the organs that might represent as well?
So I'm going to ask Jason to speak to this because in Jason we recruited Someone that did some of the fundamental work on Tregs. But the for the kidney transplant, It is about 20% have mismatches and that means that there is a substantial population of patients Who are getting an HLA A2 mismatch that our CAR Treg can be taken to by its GBS to find AHLA to and activate it no matter what the other mismatches are in the renal transplant. That's the beauty of this system. But Jason, do you want to talk about our general strategy for T. Rex?
Sure. Thanks, Andy. Yes. I mean, I think one of the things that's critical to keep in mind here is that Sangamo is really pioneering this The work that we're talking about is the first opportunity to test engineered CAR Tregs in humans. And so the opportunity to use the A2 mismatch presented just a very kind of elegant way to approach The tissue targeting because we know that the A2 molecule will only be present on the transplanted kidney by virtue of the design of the trial.
So that's the real reason for using the A2 approach. But I think one of the really exciting things about The CAR Treg platform, especially in regards to the subject of your question, which is the antigens that we pick for CAR targeting is that we are able to pick targets that, as I highlighted, are Connected to the disease etiology or simply just, tissue specific target. And that's a real advantage for us versus some of the problems that we see in the CAR T field on oncology, where identifying targets that are unique to the cancer has become a real challenge. And so we were able to either use something that is connected to the disease pathology or simply find something that is an antigen that's expressed in the tissue where we want the Tregs to localize to. And as the we're gaining a huge amount of knowledge and understanding by advancing the PX200 program And we're going to and we intend to build upon that knowledge in refining which targets we pick for future programs.
And so that's why we're keeping the opportunity to pivot to different targets by advancing multiple targets in each of these indications.
Got it. And just a quick follow-up on that in the steadfast study and following up on a previous question. As we think about the 2 secondary endpoints that you have on Slide 12, especially the ability to reduce immunosuppressive Therapy. Given that the regimens, I guess, can vary from center to center, How will we quantify reductions in immunosuppressive therapy as part of this protocol, especially and the reason I'm asking is it's my assumption that this might be the 1st needle to move. Is that a correct assumption or could acute graft rejection generate the first of the efficacy signals between those two bullets?
The advantage of modern medicine is patients rarely lose their kidney. The way they avoid that is with Immunosuppression, which comes with all kinds of health consequences. This is a cutting edge State of the art study that has to allow normal standard of care by the investigators. Of course, we would love everyone to take the same thing, but the study would not progress without that. And so we will gather the information We'll gather information from renal biopsies.
We'll understand about the Tregs. We'll watch what they do when what happens when they reduce their immunosuppression and we'll use that to design the next study and the next part of this program.
Got it. Thanks for taking the questions.
Thank you. Our next question comes from the line of Ben Burnett from Stifel. Your line is now open.
Hi, this is Kelly Breese
on for Ben Burnett. Just had one quick one about TX200. I was just wondering if you could provide any additional color about the starting doses that we may expect to see at the first look at data. If you could provide any other color on
We haven't talked about the doses, which will be some we're going to do 3 doses and it will be some number of cells that we will talk about Later, but we haven't said anything else.
Okay. Awesome. Thanks for taking my question. Thank you. Our next question comes from the line of Andreas Arderas from Wedbush Securities.
Your line is now open.
Good afternoon and thank you for taking our question. This is Andreas on for Liana Moussatos. With regard to the ASGCT abstracts, have the respective partners selected a lead candidate yet from the library generated? And when might we see these assets
Our partner program sets down to our partners to talk about them. We work closely with them. We sit on steering committees with them. And so but the rules of the relationship is for them to talk about it.
Okay. So how should we or investors look at the abstracts being presented from a scientific standpoint?
From a scientific standpoint, I think it's very fair. And but I want to assure you that our partners are excited by the progress of the CNS Assets and we look forward to speaking more about them in the future.
Okay. Thank you. Appreciate it.
Thank you. Our next question comes from the line of Debjit Chhatrapadhy from Guggenheim Securities. Your line is now open.
Hi, guys. Thanks for taking my question. This is Aaron on for Debjit. So we noticed from the Fabry clinical trial entry that the patients must have cornea, verticulitis, agro paresthesia, anhidrosis or angiocarcinoma be included. So can you tell us any estimate of the percentage of
So Bettina, this feels like one for you.
Yes. Thank you, Sandy. So as you rightly point out, clinicaltrials.gov, We have listed the inclusion and exclusion criteria for our Fabry STAR study. And the symptoms you Listed, zirconia verticillata, agrophyroesthesia, anhidrosis, endokeratoma, these are Symptoms that are classic of Fabry patients, they are patients need to have At least one of those symptoms, if not more, should be able to be enrolled into the study. And that is to ensure that Beyond the documented diagnosis of Fabry disease, we are enrolling patients who do have the underlying condition.
Okay, great. Thank you.
Thank you. At this time, I'm showing no further questions. I would like to turn the call back over to Sandy McRae, CEO, for closing remarks.
Thanks so much. This is Erin. I'll take that. So thanks once again everyone for joining us today and for your questions. We look forward to keeping you updated on our future developments.
Have a great afternoon.
This concludes today's conference call. Thanks for participating. You may now disconnect.