Sangamo Therapeutics Inc

NASDAQ:SGMO

Earnings Call Transcript 2023-Q1

[Operator]

Good day and thank you for standing by. Welcome to the Sangamo First Quarter 2023 Teleconference Call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. [Operator Instructions]. Please be advised that today’s conference is being recorded. I would now like to hand the conference over to your speaker today Louise Wilkie. Please go ahead.

[Louise Wilkie, VP, IR and Corporate Communications]

Thank you. Good morning. I'm Louise Wilkie, Sangamo's Vice President of Investor Relations and Corporate Communications. Thank you for joining us on the call today. On this call are several members of Sangamo executive leadership team, including Sandy Macrae, Chief Executive Officer; Mark McClung, Chief Operating Officer; Prathyusha Duraibabu, Chief Financial Officer; Jason Fontenot, Chief Scientific Officer; Nathalie Dubois-Stringfellow, Chief Development Officer; and Bettina Cockroft, Chief Medical Officer. Slides from our corporate presentation can be found at our Website, sangamo.com under the Investors & 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 the therapeutic and commercial potential of our product candidates, the anticipated plans and time lines of Sangamo and our collaborators for initiating and conducting clinical trials, screening, and dosing patients and presenting clinical data, advancements of our product candidates, advancements of preclinical programs to the clinic, our strategic reprioritization and restructuring and the anticipated benefits thereof. The sufficiency of our resources, cash runway, and plans to seek additional capital, our preliminary estimated operating results for quarter-ended March 31, 2023, estimated financial guidance and targets for 2023 and beyond, upcoming catalysts and milestones, and other statements that are not historical facts.

Actual results may differ materially from what we discussed today. These statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC specifically on our annual report on Form 10-K for the fiscal year ended December 31, 2022 as supplemented by our quarterly report on Form 10-Q for the quarter ended March 31, 2023 to be filed with the SEC. The forward-looking statements stated today are made as of this date, and we undertake no duty to update such information, except as required by law. On this call, we discuss our non-GAAP operating expenses. Reconciliation of this measure to our GAAP operating expenses can be found in our press release, which is available on our website.

Now, I'd like to turn the call over to our CEO, Sandy Macrae.

[Alexander D. Macrae, President and CEO]

Thank you Louise and good morning to everyone joining the call. At target is where Sangamo is today, I am proud of our rich history of scientific innovation and industry firsts. We are committed to developing genomic medicines have the potential to transform the lives of patients and to bring value for shareholders. In so doing we have been driving forward important programs in our pipeline which are producing promising results.

Today I want to sit back and spend some time reiterating the vision for the company and why we believe Sangamo has the potential to create significant value in these areas of chosen focus. I will then outline a strategic reorganization that is being announced today to prioritize resources and spend in an effort -- to achieve our vision. We will advance our wholly owned neurology portfolio of preclinical assets that leverage the power of our Zinc Finger epigenetic regulation technology, underpinned by strong capsid delivery capabilities. Anchored by our newly on field NAV 1.7 program for the treatment of chronic neuropathy pain and the Prion program for the treatment of Creutzfeldt–Jakob disease, we believe these targets are addressable today with existing technology and present both large, unmet medical needs as well as market opportunities. We believe our ability to repress or enhance the repression of genes is ideally suited to address challenging and often devastating neurological disorders creating a promising portfolio which has the potential to result in 190 submission a year, over the coming years.

At the same time, we continue to advance our industry leading Fabry and TX200 CAR-Treg clinical programs. Both of which have the potential to provide significant benefits to patients and value to shareholders. We are leading gene therapy in development to treat Fabry disease with competitors continuing to announce the pausing or termination of programs. We believe Sangamo is ideally placed to address some needs of this important patient population. The promising safety and efficacy data we have presented today reinforces the potential of this program and we are making good progress in preparations to consult the FDA on the proposed Phase 3 trial design in the summer once we have the data needed to support these conversations.

Sangamo is also a leader in the CAR-Treg cell therapy space, being the only known company to those patients in a clinical trial. Through our TX200 STEADFAST study, we believe renal transplant is the ideal model for a CAR-Treg proof of concept and if safety and efficacy are adequately demonstrated, CAR-Tregs could be well suited to treat a broad range of autoimmune indications, holding great promises and new treatment modality. We believe that our advanced Treg R&D capabilities coupled with our manufacturing know how places us in an ideal position to continue to be a leader in the CAR-Treg cell therapy field.

To date, we have seen signs of success in more assets than the company can take forward alone, which is a very rare position for a company in this industry to be in. This requires focus and a disciplined approach to using data to inform what to progress while also considering the commercial potential of each asset. While we must focus on progressing the signs and delivering for patients, we must also manage our business by carefully investing resources and generating capital to fund it for the long term with the goal of creating meaningful returns for our shareholders.

In recent months, a number of factors including general access to capital have challenged the broader market in Sangamo, requiring us to critically evaluate next steps for programs and make difficult but necessary decisions to prioritize investments and reduce cash burn. We are not the only ones being prudent with our resources as others in the industry seek to maximize near term value and rationalize their R&D spend. Therefore, today we're announcing a sharp and strategic focus with investments being carefully prioritized to advance three key areas; one, our newly unveiled NAV 1.7 and Prion programs as our prioritized wholly owned neurology portfolio; two, our Fabry program to a potential Phase 3 clinical trial; and three, the TX200 CAR-Treg program in renal transplant through Phase 1-2. We believe these are the core value drivers for the business.

With the upcoming return of the programs from Biogen and Novartis set within the wider economic backdrop, we had to carefully select which neurology programs to take forward while also reevaluating how we resource our strategic priorities. We have prioritized specific neurological epigenetic regulation targets that we believe can be delivered today through existing capsids underlying the importance of our capsid evolution program to drive future value for the company and are advancing these programs to potential IND. This has led to difficult but necessary decisions to step away from some preclinical assets as well as significantly reducing our internal manufacturing and allergenic research footprints in California. We recognize internal manufacturing especially in California as an expensive and resource intensive asset.

So at this time we believe our spend should be focused on clinical and preclinical activities which we expect to value -- to drive value in the near term. We are therefore announcing today the elimination of approximately 120 roles at Sangamon in the U.S., representing 27% of the current U.S. workforce. The restructuring plans plus other plans cost reduction initiatives are expected to result in annualized savings of approximately $31 million. We believe that these changes in combination with other cost reduction initiatives will allow us to fund our planned operations for at least 12 months. We will continue to assess ways to reduce our annual operating expenses consistent with the priorities, objectives and the progress of the company.

Alongside these announcements and with real personal sadness, I share that Andy Ramelmeier, Executive Vice President of Technical Operations, will be leaving the company. Andy has brought great passion and dedication to Sangamo building a manufacturing organization that has allowed us to support the advancement of four programs into clinical development. His technical expertise is recognized throughout the industry and his leadership is known by us all here. He leaves a legacy of technical excellence at Sangamo. Phillip Ramsey, our current head of technical development, has been appointed to serve as the Head of Technical Operations effective May 29th. I really look forward to working with Phillip as we continue to advance and align our manufacturing capabilities with our strategic priorities.

On a very personal level, these decisions have been extremely difficult. Sangamo has many brilliant and talented individuals who are and have been committed to our mission and have been instrumental in helping us achieve so many innovations during the years, I've been responsible for this great company. I'm truly thankful for their dedication and for their service to Sangamo, but no matter how difficult these decisions are, as a leadership team, we believe that they are the right decisions and we are committed to acting upon them. They will preserve our future by focusing and redeploying our capital to our most promising projects. I'd now like to turn the call over to our Chief Scientific Officer, Jason, who will share more on the vision for the neurology pipeline. Jason.

[Jason D. Fontenot, SVP and Chief Scientific Officer]

Thank you, Sandy and good morning to everyone on the call. Here at Sangamo, we strongly believe in our scientific capabilities, our platform, and the potential of our programs to help transform the lives of patients. Our Zinc Finger technology possesses important benefits over other editing modalities being explored, and we are seeing promising evidence from across our clinical and preclinical portfolio. That being said, as you heard Sandy outline, we believe now more than ever in the need to limit the number of initiatives we are undertaking at one time by focusing on advancing our prioritized neurology portfolio, Fabry to Phase 3 and our TX200 CAR-Treg clinical study through Phase 1-2.

I will start by outlining our portfolio of preclinical programs to treat neurological disorders to dive deeper into why we see significant value ready to be unlocked in these important assets. Our neurology pipeline leverages Sangamo's proprietary Zinc Finger gene targeting technology, a high precision genomic engineering platform. It is highly versatile, extremely customizable, and very compact. Once delivered. Our epigenetic transcriptional regulators are capable of repressing or activating the expression of target genes for therapeutic benefits without the introduction of mutations, breaks, or other permanent changes to the genome. Thus, they're well suited to address neurological diseases.

To maximize our probability of success and build long-term value we have designed a strategy that focuses on diseases that can be treated with the delivery capabilities we have in hand existing AAV capsules. We're currently focusing on developing novel AAV -- we are concurrently focusing on developing novel AAV capsids that we believe will greatly broaden the set of indications addressable with our technology in the future, including high value neurodegenerative diseases such as Alzheimer's disease. We believe this wholly owned neurology portfolio has the potential to result in one IND submission a year over the next few years.

Today, we unveil the flagship program of our wholly owned neurology pipeline NAV 1.7. Using an optimized Zinc Finger epigenetic represser we will specifically target and seek to reduce NAV 1.7 expression in dorsal root ganglions to inhibit pain sensations in diseases of chronic neuropathic pain. Despite being a highly validated target, NAV 1.7 has evaded small molecule or antibody therapeutic manipulations due to very challenging specificity issues. By contrast, our Zinc Finger epigenetic repressors have demonstrated potent and highly selective repression of NAV 1.7 expression up to 99% per cell, paired with a high degree of specificity even among NAV 1.7 most closely related receptors.

Our initial focus will be NAV 1.7 associated small fiber neuralgia with an estimated prevalence of at least 43,000 patients in the U.S. We believe we can specifically prevent the transmission of nociceptive pain signals to the brain and believe initial success in treating small fiber neuralgia would subsequently enable us to broaden use of this therapy to other neuropathic pain indications regardless of the cause of pain. Importantly, reducing pain by inhibiting NAV 1.7 is not known to be associated with any other neurological side effects and other sensory modalities are not expected to be affected. Detailed preclinical data from this program will be shared via platform presentation on May 17th at the upcoming American Association of Gene and Cell Therapy Annual Meeting in Los Angeles. We are anticipating an IND submission for the NAV 1.7 program in 2024.

Beyond NAV 1.7, we continue to advance our wholly owned neurology program targeting the Prion protein for the treatment of Creutzfeldt-Jakob disease. At the Prion 2022 conference last September, we reviewed data demonstrating that our approach to targeting neurological pathologies with Zinc Finger repressors is effective. Our Prion targeted therapy reduced the expression of Prion by 40% to 60% in the brains of mice, reducing toxic Prion aggregates that drive neuronal degeneration. This data developed in collaboration with the Massachusetts Institute of Technologies’ Broad Institute demonstrated that the therapeutic administration of our Zinc Finger epigenetic repressors significantly extended survival of Prion infected mice through to 500 days, the typical lifespan of a mouse. Importantly, the effect was superior to published ASO treatments. This data provides validation of our work in Prion disease, but more importantly for our entire neurology targeted Zinc Finger epigenetic repressor portfolio.

Prion disease represents a group of conditions with a devastating unmet medical need at this time, which we believe our technology can address. This disease is rapidly progressive and always fatal, usually within one year of onset of illness. Our intent is to target symptomatic, hereditary, sporadic, or acquired Creutzfeldt-Jakob disease, which has an incidence of approximately 500 patients per year in the U.S. The impressive data generated to date is fueling our ongoing development of the Prion program with a potential IND submission expected in 2025.

Delivery to the central nervous system is a major hurdle for clinical application of genomic medicine. The blood-brain barrier limits the brain wide distribution of intravenously administered macromolecules. To overcome this issue we have developed a proprietary AV capsid discovery platform called SIFTER. SIFTER allows us to engineer AV capsids with the potential for highly improved central nervous system transduction efficiency. Using SIFTER we have identified what we believe are the first of many novel AV capsids, Stack 102 and Stack 103, which have demonstrated high efficiency delivery to the brain. This capsid innovation work is broadly enabling our entire neurology pipeline and we expect will also provide valuable revenue generation opportunities through potential partnerships. I'm very pleased with the progress we have made and look forward to sharing more about our AV capsids in the near future.

With regards to our partner neurology programs, we received notice this quarter that both Biogen and Novartis have decided to terminate collaborations with us. While completely unrelated, these two decisions had an unfortunate coincidental timing coming in the same week. In both cases, these decisions resulted from strategic portfolio reviews seeking to balance value, growth, and risk. This is reflective of broader trends in large pharma to step away from early stage risk and prioritize investment in de-risked late stage and commercial product. While we understand these decisions, Sangamo’s focus is bold discovery to create transformational medicines. In pharma such work is out of favor as companies look for cost savings. We are pleased with the progress of these programs and look forward to sharing preclinical data from them in the near future.

Most notably, exciting work demonstrating epigenetic Zinc Finger activator capabilities for the first time. These programs will be returned to Sangamo upon completion of the three month termination activities. After a comprehensive review of our portfolio, we have recently made the strategic decision to pause these previously partnered programs and instead focus our efforts on our wholly owned pipeline programs. We look forward to potentially revisiting these targets and indications as our SIFTER platform identifies new AAV capsids to facilitate the delivery necessary for success in these indications. Notably, the programs returned to us from Biogen and Novartis have generated 425 million in cash for us and are now significantly more advanced, thereby driving significant future value opportunities for Sangamo and our neurology focused pipeline.

I will now turn the call over to Chief Operating Officer Mark, who will contextualize the broader pipeline and progress in our key clinical assets. Mark.

[D. Mark McClung, EVP and COO]

Thank you Jason, and good morning everyone. Starting with Fabry, we remain the leading gene therapy in this space with yet another competitor recently announcing the termination of development. This underscores the need for us to double down and continue working tirelessly to make this medicine available to those living with Fabry disease. As we actively prepare for a potential Phase 3 trial, it's helpful to remind everyone of the market opportunity for this asset. We know that there are approximately 4,000 diagnosed Fabry patients in the United States as well as many more that are not diagnosed even with familiar incidence of the disease. Of those diagnosed around 1300 to 1900 are actively on treatment like enzyme replacement therapy although many struggle with the adherence to the regimen. We have successfully recruited naive pseudo naïve patients into our Phase 1-2 study, as well as patients already on ERT, which demonstrates the desire of patients to have alternative and improved treatment options over and above the standard of care. We will therefore continue to appropriately invest in this program to maximize the chances of clinical and commercial success.

The compelling data we shared last quarter from the STAR study demonstrated a favorable safety profile and evidence of clinical benefit from strong biomarker data to kidney biopsies and improved SF-36 general health scores. Since Q4 earnings, we have dosed a further three patients in the Phase 1-2 study to achieve a total of 20 patients to date, and we continue to enroll in this study. We strongly believe ST-920 is a potential medicine, so we're progressing Phase 3 planning with urgency and plan to meet with the FDA on the proposed study design this summer once we've accrued sufficient data for those discussions. The trial is anticipated to commence in the second half of 2023 and dosing of the first patient could happen as early as the first part of 2024, depending on the regulatory interactions. As a reminder, the expansion Phase 1-2 for which we expect to complete dosing in 2023 is not expected to be a gating factor for the commencement of the Phase 3, but will provide additional data, to support the regulatory package.

Now turning to our CAR-Treg portfolio, where once again we're a leader in this field of research and in the clinic. When we acquired TXL in 2018, we gained deep expertise in regulatory T-cell biology and married that with our detailed understanding of manufacturing and our experience developing INDs and progressing programs into clinical development. With these factors combined, we believe we are well placed to maximize the opportunity for CAR-Tregs to treat a range of autoimmune indications and are pioneering a new type of treatment modality. The first of the programs, TX200 and HLA-A2 mismatch kidney transplantation continues to move through the clinic. This quarter we dosed the third patient in Cohort One, and all patients continue to do well. Preparation for the second and higher dose cohort is actively progressing, and we have additional patients in pre-screening who continue to enroll.

As we outlined on the last quarterly call, we've been working to accelerate the pace of enrollment in this study. I'm pleased to announce that we've received positive initial feedback from two European agencies required for the enhanced trial design that will accelerate dose escalation. We're also on track to share clinical data from Cohort One by the end of 2023. As part of our sharpened focus, we plan to prioritize the investment of our near-term autologous CAR-Treg portfolio, and this has resulted in a decision to transition all allogeneic research activities from the United States to our Valbonne, France facility to see self-manufacturing in our Brisbane, California facility. While allogeneic capabilities will be important to the long-term development of the CAR-Treg platform, it's important that our resources are directed towards advancing TX200 at this time.

Finally, I want to reiterate two other important components of the story that we expect to be value drivers for the company. The first is giroctocogene fitelparvovec an investigational gene therapy we're developing with Pfizer for patients with moderately severe to severe hemophilia A currently in Phase 3. Dosing is complete for all patients required to complete the primary analysis and Pfizer continues to work towards a pivotal read out expected in mid-2024. Pfizer anticipates the potential BLA and MMA submissions in the second half of 2024, which when completed would generate a significant milestone payment. As a reminder, this partnership agreement allows for a potential milestone of up to 240 million and up to 14% to 20% in potential royalties.

The other important potential value driver of our portfolio is innovative new capsids that Jason outlined earlier, and which serves as a resource to address the issue of delivery to places like the central nervous system. We recognize the importance of unleashing the potential of new engineered capsids as enablers of genomic medicines, both for our own programs and those with potential partners, and are making significant progress in addressing delivery to a range of previously inaccessible areas. We see this asset as a source of competitive advantage and also potential revenue, and are hopeful to share some exciting updates about our capsid program over the coming months. I'll now turn it over to our Chief Financial Officer, Prathyusha for an overview of the financial results. Prathyusha.

[Prathyusha Duraibabu, SVP, Principal Accounting Officer and CFO]

Thank you, Mark and good morning everyone. Sangamo announced preliminary first quarter financial results yesterday as we worked towards completing customary quarter end close and review procedures including the evaluation of non-cash charges related to impairment of long-lived assets. Our preliminary results are as follows, revenue for the first quarter ended March 31st, 2023 are estimated to be approximately $158 million compared to $28 million for the same period in 2022, reflecting an increase of $130 million year-over-year. This was primarily driven by the return of assets from Biogen requiring us to accelerate approximately 121 million of non-cash revenue from the related upfront fees.

Total GAAP operating expenses for the first quarter are estimated to be in the range of $120 million to $140 million compared to $73 million for the same period in 2022, reflecting an increase of $47 million to $67 million year-over-year. This was primarily driven by certain non-cash charges including goodwill impairment of $38 million and estimated impairment of long lived assets of up to $20 million. These impairments were driven by several factors, including termination of significant partner agreements noted previously and lower market capitalization similar to what other companies in our space have observed.

We ended the quarter with approximately $241 million in cash, cash equivalents, and marketable securities, which is expected to fund the company for at least the next 12 months. This represents a decline of approximately $66 million from the prior quarter. Furthermore, the headcount reductions announced today in combination with other planned cost reductions are expected to result in annualized savings of approximately $31 million going forward. We continue to assess ways to further reduce our annual operating expenses and to manage Sangamo as a highly focused organization driving towards our prioritized two neurology assets Fabry and TX200.

As a result of these changes our previously announced 2023 non-GAAP operating expense guidance range of $275 million to $295 million is now obsolete. We expect a current estimate for 2023 to be in the range of $240 million to $260 million. This range excludes certain non-cash charges including estimated [indiscernible] impairment of long lived assets and stock based compensation expense. Sangamo is assessing ways to further reduce operating expenses in line with our strategic priorities and the readouts from key programs will continue to drive physicians and investments in the coming months. In parallel, Sangamo is committed to creating long-term value for our shareholders, and we will continue to proactively and intensively explore avenues to raise additional capital, including through partnerships. I will now turn the call back to Sandy for closing remarks. Sandy.

[Alexander D. Macrae, President and CEO]

Thank you, Prathyusha. Today you heard that Sangamo is being responsible, responsive, and nimble in order to position ourselves for future success. There's a lot to look forward to. With Hemophilia A marching closer to a potential BLA submission. Today we announced our wholly owned neurology portfolio centered around NAV 1.7 with a IND submission anticipated in 2024, leveraging our innovative sync finger technology and underpinned by a capsid development capability that we believe can provide value in the near and long term. Our market leading Fabry program advances towards a potential Phase 3 trial expected to begin at the end of this year, and our first in class CAR-Treg technology is being assessed in the clinic through TX200 with initial data from Cohort One expected by the end of 2023.

I'm very thankful to our leadership team and all my Sangamo colleagues for their hard work and dedication to our mission. I'd like to close by expressing my hope and excitement for the future that lies ahead for Sangamo. So at this time, we'd like to open up for questions. Operator, please open the line for questions.

[Operator]

[Operator Instructions]. And our first question will come from Ben Burnett of Stifel. Your line is open.

[Benjamin Burnett, Stifel]

Hey, thank you very much. I had a question regarding the Fabry program. I was wondering if you could provide more color on the potential Phase 3 design being proposed to the FDA and is there any expectation that Fabry would be needed as a comparator? And I guess if so, any thoughts as to whether or not a non-inferiority study would supply for approval in the U.S.?

[Alexander D. Macrae, President and CEO]

Ben, thank you for your question. I'm going to pass that one on to Nathalie.

[Nathalie Dubois-Stringfellow, SVP and Chief Development Officer]

Yeah, hi. Thank you for the question. We are preparing the interaction with the FDA, right now. We hope to have a meeting this summer and we will comment on the Phase 3 design and potential agreement with the FDA after the call.

[Benjamin Burnett, Stifel]

Nathalie what gating are going to that interaction?

[Nathalie Dubois-Stringfellow, SVP and Chief Development Officer]

Some additional data from our top dose in the Phase 1-2 trial, but we are…

[Alexander D. Macrae, President and CEO]

So it's simply just the time of collection of data.

[Nathalie Dubois-Stringfellow, SVP and Chief Development Officer]

Absolutely.

[Benjamin Burnett, Stifel]

Okay. That makes sense. I appreciate that. And maybe if I could also just ask a question, like a biology question actually on the Prion disease program. I think the way the slide is depicted as we understand it, Prion proteins, I guess, are continually supplying like material for the production of these larger misfolded aggregates. Is there anything known about whether aggregates will be cleared once the Prion source is turned off, what have you unveiled there?

[Alexander D. Macrae, President and CEO]

Jason, can you help with that please?

[Jason D. Fontenot, SVP and Chief Scientific Officer]

Yes. There is evidence that if the source of the Prion protein aggregates the gene, the Prion gene if turned off that aggregates do diminish. So, we believe that this approach will have therapeutic potential, and indeed the data that we have presented at Prion 2022 showed great effects in the preclinical mouse models. So we were very excited about this program.

[Benjamin Burnett, Stifel]

And Jason, can you just summarize that data quickly about the difference in lifetime of mice and when the dosing was given?

[Jason D. Fontenot, SVP and Chief Scientific Officer]

Sure. So, the model that was used in that study is considered a gold standard for understanding Prion disease. And we took two approaches there, one where the mice were inoculated with the Prion protein, which initiates the disease and simultaneously treated with the Zinc Finger repressors. But we also took an approach where the mice were inoculated and then the disease was allowed to start to develop, and then that therapeutic application of the repressors was used. And in both cases our repressors extended very significantly extended the lifespan of the mice. And we compared this to data that has been published on ASOs. And, really an impressive part of this was how much improved our Zinc Finger repressors were at extending the mice lifespan.

[Benjamin Burnett, Stifel]

That's super interesting. Thank you.

[Operator]

And one moment for our next question. Our next question will come from Greg Harrison of Bank of America. Your line's open.

[Gregory Harrison, Bank of America]

Hey, good morning and thanks for taking our questions. Maybe you could give us a little background on just what led to the choice of NAV 1.7 as the target of focus and how could your approach be differentiated from others like the small molecule, blockers under development, like for a Texas program?

[Alexander D. Macrae, President and CEO]

Greg, thank you for the question. And, I'm going to pass on to Jason again to talk us through the science. But for those of us that have been in industry for any period of time, we've seen the number of companies have tried to drug NAV 1.7 and struggled with the fact that small molecules and antibodies that work on NAV 1.7 and give clear benefit in pain, interact with similar proteins such as NAV 1.6, NAV 1.8, and cause side effects. So Jason, why do we think our approach is so fundamentally different?

[Jason D. Fontenot, SVP and Chief Scientific Officer]

Yeah, so what's so exciting about NAV 1.7 is that there is very clear genetic data from human populations that show that this molecule is a key regulator of pain sensation. So it has a very clear genetic, it's genetically implicated in diseases. But as Sandy pointed out, the problem with targeting NAV 1.7 has been that there it is part of a family of very closely and structurally similar receptors and small molecule approaches in particular have been unable to specifically target NAV 1.7 without involving other receptors. And this creates issues of specificity. So what's unique about our Zinc Finger program is that we can design an epigenetic repressor that very specifically targets NAV 1.7 without affecting the expression of any of the other closely related receptors. And this allows us to do what small molecules or antibodies can't do, which is only target NAV 1.7 and achieve this reduction in pain transmission without affecting the other processes that are regulated by the closely related receptors.

[Alexander D. Macrae, President and CEO]

I want to just underline that and take it to a kind of simpler level. The small molecules target the protein. What we do is we target the DNA and the DNA target for NAV 1.7 is completely different from all the other NAVs, and therefore we do not have this problem of specificity because it's the DNA that we target and not the protein. Does that help Greg?

[Gregory Harrison, Bank of America]

Yeah. Yeah, that's super helpful. If I could sneak one more, just curious, now that you're focusing on the 1.7 program and other earlier stage programs like CAR-Treg, will you seek partners to help fund development and just broader, what's your strategy for funding the pipeline in the more medium to longer-term?

[Alexander D. Macrae, President and CEO]

That's a very fair question. Mark, can you help with that?

[D. Mark McClung, EVP and COO]

Sure. Hi, Greg. Thanks for the question. As we've communicated before, we're excited about our technology and when we get approached by potential partners that are interested in it, we really ask ourselves a couple of questions. One is, can the partners help us accelerate the program faster to patients by bringing resources, expertise, and capabilities. And if they do, then that we take a serious look at that. I mean, we've got a strong history over the last several years in terms of partnerships that have brought in about 815 million in upfront. And, we've seen a lot of progress as a result of those partnerships including Pfizer's advancements that I've commented on earlier. So we will look at that.

[Gregory Harrison, Bank of America]

Great. Thanks for taking the question.

[Operator]

And one moment for our next question. Our next question will come from Gena Wang of Barclays. Your line is open.

[Gena Wang, Barclays]

Thank you. I also have one question regarding NAV 1.7. I think it's also expressing actually, quite different tissues as well, like pancreatic beta cells and olfactory sensory, there are a few other parts of the body. So wondering, several questions. One is, what is advantage or disadvantage of a long-term incubation and what is your route of administration and how good is the selectivity regarding the specific organ?

[Alexander D. Macrae, President and CEO]

So there is three questions, Gena, that I heard. One is about route of administration, one is about specificity, which I think we partly addressed. And the other one is about long-term benefit to the patient. So between Jason and Nathalie, can we address this. So Jason, do you want to talk about the specificity please and the route of administration?

[Jason D. Fontenot, SVP and Chief Scientific Officer]

Sure. Thank you for the question, Gena. I think there are two important points about the specificity. First, this is where the power of our Zinc Finger genomic engineering platform really comes to the front. We are able to design Zinc Finger epigenetic repressors that are highly specific for NAV 1.7 and avoid repression of any of the closely related receptors. But in addition to that, in the AV vector that delivers this cargo, we also can use promoters that are specific for the cell type that we're interested in driving that repression. So by -- through the combination of both of those mechanisms, we are able to achieve very selective expression in the tissues that we are interested in targeting, specifically here, the dorsal root ganglion. So that's really the key to how we can achieve really exquisite specificity for both the target and the cell type is through the combination of our Zinc Finger gene targeting capabilities and our promoter engineering capabilities.

In terms of delivery for the dorsal root ganglion, we can achieve delivery through systemic administration. And so that is the approach that we are taking.

[Alexander D. Macrae, President and CEO]

Through systemic administration?

[Jason D. Fontenot, SVP and Chief Scientific Officer]

Sorry, excuse me, intrathecal administration.

[Alexander D. Macrae, President and CEO]

Nathalie, do you want to comment on that?

[Nathalie Dubois-Stringfellow, SVP and Chief Development Officer]

Yes. So yeah, we are targeting a population of patients with so small fiber neuropathy that have chronic diseases. So we hope that the treatment will last for a long time. It's a one-time single intrathecal bolus injection of the product and we intend to do a dose escalation trial that will allow us to target the appropriate dose for reducing the pain in those patients.

[Jason D. Fontenot, SVP and Chief Scientific Officer]

And these are patients, this group that we're targeting as our first population are people with intractable pain, their lives are dominated and ruined by their intractable pain, we've had them come visit us for the company. By doing it intrathecally, by doing it with a promoter that specific NAV that is only going to appear in the run to dorsal root ganglion and by Zinc Fingers it will only repress a single gene. We get an enormous specificity benefit, we will show results at ASTCT about animal experiments that show the benefit on pain. And we really feel that there's a route forward here for what is an important, significant medical unmet need.

[Nathalie Dubois-Stringfellow, SVP and Chief Development Officer]

And importantly I think, I may add that reducing pain by integrating NAV 1.7 is not known to be associated with any neurological side effect and other sensory modality are not expected to be affected. So very specific targeting, yeah.

[Gena Wang, Barclays]

So yeah, my question also like long term inhibition, what could be the disadvantage there?

[Alexander D. Macrae, President and CEO]

So, we will do this, Gena you know us well, and you know how seriously we take patient benefit and patient safety. And so we will start at the appropriate dose agreed with the agency and gradually increase it. But I cannot say importantly enough, how seriously impacted these patients are by their pain. And so for them this is an enormous advantage. And we've consulted with them, we've had them come into the companies and they see this as a really promising future medicine.

[Gena Wang, Barclays]

Thank you.

[Operator]

One moment for our next question. Our next question will come from Maury Raycroft of Jeffries. Your line is open.

[Maury Raycroft, Jefferies]

Hi, good morning. Thanks for taking my questions. Maybe as follow up to Gena’s question, you mentioned the cell specific promoter and intrathecal delivery. Can you talk more about capsids as a gating factor for program advancement, I guess I would like to clarify that for the previously partner Biogen and Novartis programs, one of the reasons why those are paused for now is primarily because of a) the delivery limitations and will you use a novel CMO capsid for NAV 1.7 and Prion or conventional capsid like [indiscernible] because you need less blood brain barrier penetration and distribution for those targets?

[Alexander D. Macrae, President and CEO]

Good morning, Maury. Thank you for the questions. So we're not revealing which capsids we are using for which diseases at this time. But we believe that we have a solution for each of the ones that we're advancing. Looking at -- talking about the Biogen Novartis programs, for example. Alzheimer’s, the challenge for that is ensuring that we have widespread brain coverage, particularly for the regions that are most impacted by Alzheimer's in an intravenous manner we believe. And so we've paused that program, it has advanced significantly over the three years it's been with Biogen, we are making great strides with our captured evolution, we are watching with interest other people's capsid evolution change. And when there is progress, and I truly believe there will be progress in a blood brain barrier crossing capsid in the soon future, those assets suddenly become very attractive for us or for other people.

[Maury Raycroft, Jefferies]

Got it. That's helpful. Thanks for taking my questions.

[Alexander D. Macrae, President and CEO]

Thank you Maury.

[Operator]

One moment for our next question. And our next question will come from Yanan Zhu of Wells Fargo. Your line is open.

[Yanan Zhu, Wells Fargo]

Hi, thanks for taking our questions. On the NAV 1.7 program, just wondering what percentage of suppression of expression are you driving for and expecting to have benefits? And also, is there -- are there advantages for using transcription repressor approach as opposed to straight knockout approach since you have both technologies? Thanks.

[Alexander D. Macrae, President and CEO]

Jason, this sounds like a technical question for you.

[Jason D. Fontenot, SVP and Chief Scientific Officer]

Yeah, thank you for the question. So maybe I'll start with the second question. We are really excited about our epigenetic repression platform. And we believe that it's really optimal for this particular approach for a few reasons. One, because we're allowed -- we're able to regulate the genes without the introduction of double stranded breaks, or any type of mutation, and we're able to do that very specifically and very potently. So we've achieved what is essentially 99% close to quantitative repression of the target gene using this approach, and we believe it will be stable for the long term. So we're very excited about the approach and believe it's superior, especially in the CNS, where cells are non-dividing, than using the nucleases for instance, or any kind of approach that modifies the DNA permanently.

Regarding how much repression is needed, I think there's two things to be considered there. There's the Purcell repression, and the coverage, the number of cells that are being repressed. What's really great about our platform is that on the Purcell basis, we can design repressors that repress gene expression to the amount that we think is needed to achieve the biological and therapeutic effect. And so we've identified repressors that are very potent at the single cell basis. And then through dosing and animal models, we will explore what level of repression across multiple cell types is necessary to achieve the appropriate therapeutic reduction in pain. And that will be done by dosing in preclinical models to understand what range of doses we want to explore, and then we'll take that into patients.

[Yanan Zhu, Wells Fargo]

Got it. Thank you. And maybe also a question -- maybe two quick questions, one on the Fabry disease program. Could you comment on whether those patients who were off ERT remains off at this moment or should we -- do we have to wait until the next data update to hear about that? Thanks.

[Alexander D. Macrae, President and CEO]

Nathalie, can you update that?

[Nathalie Dubois-Stringfellow, SVP and Chief Development Officer]

Yeah, so far, all the patients that have been withdrawn from ERT are still of ERT.

[Yanan Zhu, Wells Fargo]

Very helpful. And lastly for the TX200 program, will you move to a higher dose sometime this year, because it sounds like I think the first cohort I designed is designed to have three patients and sounds like you have those three. So could you talk about potential decisions for dose escalation there? And yeah, I think, yeah, that's a question.

[Alexander D. Macrae, President and CEO]

Bettina, can you help with that?

[Bettina M. Cockroft, CMO]

Yes, absolutely. And thank you for the question. So we're extremely happy to have concluded enrollment and dosing in Cohort One. For TX200, we plan to have a safety monitoring committee meeting, coming up very shortly in May so that we can then move on to the next cohort. And we already have patients lined up. And we're excited by this. We have also recently engaged with regulatory agencies in Europe who are representing with countries where we're conducting the trial that have agreed to an optimized design of our dose escalation protocol. And so this means we hope to accelerate dose escalation and then we'll plan to share initial data from Cohort One by the end of this year.

[Yanan Zhu, Wells Fargo]

Got it. Thanks for all the updates.

[Operator]

One moment for our next question. Our next question will come from Luca Issi of RBC. Your line is open.

[Unidentified Analyst, RBC Capital Markets]

Oh, excellent. Thanks for taking our questions. This is Lisa on for Luca. Maybe just one here first on the restructuring efforts announced today. Just wondering what other initiatives are being explored to either preserve capital or raise funds? And have you thought about potentially monetizing the royalty stream for Hemophilia A?

[Alexander D. Macrae, President and CEO]

Thank you for the question. The restructuring was a very important part of our announcement today. Prathyusha, can you comment on this?

[Prathyusha Duraibabu, SVP, Principal Accounting Officer and CFO]

Yes, Sandy. So today's restructuring was a difficult decision but it was in line with the strategic priorities we outlined on the call. And we'll continue to assess ways of running Sangamo as a leaner, focused organization. As far as evaluating the different levers for extending our cash runway, as a clinical company we're actively pursuing different opportunities for financing and we will look at different avenues including the royalty monetization.

[Unidentified Analyst, RBC Capital Markets]

Alright, thanks. Go ahead Sandy.

[Alexander D. Macrae, President and CEO]

It's a significant return or revenue for Sangamo in the future. And we need simply to be thoughtful about when we access that revenue. The closer it gets to submission and hopefully marketing of an important medicine, the more valuable it is. And so that's the balance that Prathyusha is constantly looking at to both near-term cash versus long-term value, all of which will lead to return for our shareholders.

[Prathyusha Duraibabu, SVP, Principal Accounting Officer and CFO]

That's right.

[Unidentified Analyst, RBC Capital Markets]

That's helpful. Thanks. And maybe just one on the Treg more of a big picture question. You announced that we are going to get some data maybe later by year end, just thinking, what are going to be the next steps for Treg, should the data be positive, will this accelerate your thinking on moving towards an autoimmune indication?

[Alexander D. Macrae, President and CEO]

Mark, can you help us think about the Tregs please?

[D. Mark McClung, EVP and COO]

Thanks, Lisa. Yeah, I mean, as we talked about TX200 we think is a perfect biologic model to assess the performance of Treg. And so we're really excited about that and we'll be looking forward to providing an update as we mentioned towards the end of the year. We do have our preclinical programs, they're continuing to progress. MOG for multiple sclerosis and IL23 for inflammatory bowel disease. Both of those programs, as we've talked about, we're focusing primarily on the autologous to ensure we can move them forward towards IND. And so we're very committed to that and excited to continue this. We've got a lot of focus to execute against the preclinical work on both of those assets as we continue to execute on the TX200 trial.

[Unidentified Analyst, RBC Capital Markets]

Thanks for taking our questions.

[Operator]

And one moment for our next question. And our last question comes from Patrick Trucchio of H.C. Wainwright. Your line is open.

[Patrick Trucchio, H.C. Wainwrigt]

Thanks, good morning. I just had a few follow up questions from a few that had been asked earlier. The first was just I was wondering if you can just talk a little bit more about the SIFTER platform and how it enables selection of CNS tropic HIV capsules, and in particular, with regard to these neuro programs, what are you actually looking for in the identification, selection of the engineered AV capsids for enhanced CNS delivery? And then just separately, just with the CAR-Treg, I'm just wondering with the intention to prioritize the near term autologous portfolio, can you please provide some additional details around this decision, how will this perhaps accelerate the INDs for the broader indications like MS and IDD?

[Alexander D. Macrae, President and CEO]

So, let's answer, Patrick, thank you for your question. Let's try and answer this in two ways. Jason, can you take capsids, please. And Mark, can you talk about Treg, please?

[Jason D. Fontenot, SVP and Chief Scientific Officer]

Sure. Thanks for the question, Patrick. So we're really excited about the work in our capsid evolution group. And I guess, I can take the question in two different ways. There's the actual technology that we're using to develop and evaluate capsids. But there's also the approach that we're taking to decide what we're looking for in capsids. And so on that second component, I want to emphasize the work that is done as a collaboration between our development groups and neurologists and our development group and our scientists in research to identify indications that we think are optimal for being addressed with the technologies that we have, specifically our Zinc Finger epigenetic platform.

So once we identify diseases where we think we can really move the needle, we think about the biology and the anatomy and where in the brain or in the nervous system needs to be targeted. And so for different diseases, those are different areas of the brain, sometimes they are areas of the peripheral nervous system. And so once we identify where we want to target, then we think, okay, what is the best capsid to do that. And we have a team that is developing capsid libraries that are both targeted. So we evaluate specific pathways that are known to facilitate transport over the blood brain barrier. And we have capsid libraries that are more randomly diversified. And we can evaluate both of those in cells and animal models to look for novel capsids that produce high frequency transduction, highly efficient transduction in the areas that we're interested in targeting for a specific indication. And so that's the approach that we use to look for novel capsules.

So we have an idea of a whole set of indications, and areas of the of the nervous system that we're interested in targeting. And we're using these libraries that can be delivered, we have some libraries that are designed to be delivered systemically. And we have other libraries that are designed to be delivered by direct injection. And we use both of those approaches to look for capsids that we think can get us to the therapeutic effect that we need. And once we have one of those in hand, and we're obviously excited to move forward.

[Alexander D. Macrae, President and CEO]

So Patrick, on the Tregs, I mean, I want to frame this in a couple of ways. One, as we all know, access to capital these days is a challenge. And as a result of that, and with the burn rate that we've had, we've had to really focus on prioritizing. And when we have to prioritize, it means we have to make choices. And sometimes there are things we would not choose to do. And in the case of the Tregs, we had to make a choice to really focus on TX200 and the execution of that trial to proof of concept and keeping them organized 23 preclinical auto programs, which are a little more advanced, moving forward. So we've had to make a difficult choice to deprioritize the LL [ph] work until the future. But you know, I want to say that our investors also say to us that they're very interested in the Tregs and they would love to invest in the Tregs. And so we're assessing how best we can set ourselves up to do that. But in the meantime, we're also looking and having conversations with interested parties around partnerships. If we ended up ended up having a partnership coming in, one of the thing we'd want them to do is bring enough money and expertise and that we can restart those programs and accelerate them again. But it's purely a choice that we've that we've had to make unfortunately.

[Patrick Trucchio, H.C. Wainwrigt]

That's helpful. Thank you very much.

[Operator]

And I'm showing no further questions. I would now like to turn the call back over to Louise Wilkie for closing remarks.

[Louise Wilkie, VP, IR and Corporate Communications]

Thank you once again for joining us today and for your questions. As a reminder, you can access the earnings release and presentation on the investor relations section of the Sangamo website. We look forward to keeping you updated on our future developments. Thank you.

[Operator]

This concludes today's conference call. Thank you for participating. You may now disconnect.