Sangamo Therapeutics, Inc.

Good morning and thank you for standing by. Welcome to the Sangamo Third Quarter 2023 teleconference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to turn the conference over to your speaker today, Louise Wilkie, Vice President of Investor Relations and Corporate Communications. Please go ahead.

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 the Sangamo executive leadership team, including Sandy McRae, Chief Executive Officer, Mark McClung, Chief Operating Officer, Pratusha Durrababu, Chief Financial Officer, Amy Pooler, Head of Research, Natalie Dubois-Stringfellow, Chief Development Officer, and Lisa Roycare, Chief Medical Officer. Slides from our corporate presentation can be found at our website, sangamo.com, under the Investors and Media section of 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 timelines of Sangamo and our collaborators for regulatory submissions, initiating and conducting clinical trials, screening and dosing patients, and presenting clinical data, advancements of our product candidates, anticipated feedback from and interactions with the regulatory agencies, advancement of preclinical programs to the clinic, our strategic reprioritization and reallocation of resources and the anticipated benefits thereof, the sufficiency of our resources, cash runway, and plans to seek additional capital, and the timing of related updates, our estimated financial guidance for 2023 and estimates of 2024 operating expenses, 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 in 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 September 30, 2023, followed yesterday with the SEC. The forward-looking statements dated 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 McRae.

Thank you, Louise, and good morning to everyone joining the call. Sangamo has a long, impressive history of scientific innovation, leading to new discoveries and industry firsts for genomic medicine. I am so honored to lead a company with such deep scientific expertise and a team so dedicated to our mission of transforming patients' life with our technology. While our programs are delivering promising results, the environment within which we are operating has been and is likely to remain challenging. In 2020, we shared our refresh company strategy, which aims to both maximize the potential of our proprietary genomic editing and delivering technology and to focus on areas where we believe we can apply that technology to be either first in class or best in class. That began with our decision to transition away from developing new traditional liver directed gene therapy several years ago and has continued into today. Our renewed focus has been to identify areas where we believe we can be market leaders and to prioritize our resources to those programs accordingly. The difficulties in accessing capital being experienced across the industry have accelerated the pace of our plans. And so today we're announcing the final stage in the strategic transformation of Sangamo to become a neurology focused genomic medicine company. As we have shared before, we strongly believe our technology is ideally suited to address a range of devastating neurological indications that are few, if any, treatment options available today. Over recent years, we've increased our focus on this important part of our business and have advanced exciting data from our epigenetic regulation programs for neurological diseases. The promising preclinical evidence from our zinc finger editing capabilities, coupled with the strong progress we're making in identifying novel capsids with enhanced delivery capabilities, demonstrates the potential for Sango to become a leader in this space. Our differentiated combination of precise, versatile, and compact genome targeting cargo, alongside our novel AAV capsid evolution engineering, which has the potential for meaningfully improved central nervous system transduction efficiency, forms the foundation from which we believe we can transform the lives of patients with neurodegenerative diseases, such as intractable pain conditions, prion disease, Alzheimer's, and many other neurological conditions. You will hear us say throughout this, it's capsid and cargo. You have to have capsid and cargo to be successful. We believe this combination of genome targeting cargo and delivery caps will be critical to a sustainable business model with our internal programs, as well as providing important potential partnership opportunities. I'll speak more about this in a moment. In order to set the neurology company up for success, We must truly focus and carefully allocate resources to those priority programmes that are central to our core strategy. This means deferring new investments related to Fabry and Urquhart T. Wright programmes, while continuing to seek ways to maximise their potential value. We're committed to these changes. It's an immensely difficult decision to deprioritise spending on our legacy clinical programmes, which have such clinical promise. I strongly believe that our Fabry disease program is potentially transformative for patients. The phase one two star study continues to generate a meaningful packet of data with 25 patients now dosed, 25 patients, including 14 at the planned phase three dose. All patients continue to demonstrate sustained elevated alpha-galli levels, with 12 patients having achieved at least one year of follow-up, and the longest treated patients having now achieved three years of follow-up is a significant achievement. Additionally, all 11 patients who were withdrawn from enzyme replacement therapy remain off enzyme replacement therapy for up to 24 months for the longest withdrawn patients. I think it's worth emphasising that these are patients who were on ERT and said to be treated. They've come off ERT and they're staying off ERT because they feel a benefit from our treatment. And they tell us about it. We have received testimonies from patients saying that the impact of ST920 has been transformative and who report real and meaningful improvements in the quality of life. Some even over and above the benefits that they were experiencing on ERT. We have shown and strongly believe in the promise of ST920 as a potential medicine for patients suffering with Fabry disease. This is first in class, currently the only gene therapy in the clinic for these patients. However, at this time we're deferring any additional investments in Phase 3 planning. The cost of progressing the program beyond the current Phase 1-2 study would constrain our resources and require significant development and commercial investments, which we do not have the ability to support at this time. We're doing everything in our power to maximise its value by actively seeking a potential partner or alternative financing to fund a potential phase three trial. We're confident that in the hands of a partner, ST920 will make an enormous difference to the Fabry community. I firmly believe Fabry patients deserve a better option than the current standard of care. We expect to complete dosing of the remaining enrolled patients in the first half of 2024 and anticipate presenting additional updated clinical data at a medical meeting in early 2024. Turning now to our regulatory T cell programs. We are proud of our efforts to advance innovation in the CAR T reg field. Since our acquisition of TXL five years ago, We have become the first known company to dose a human with an engineered CAR Treg, overcame significant manufacturing challenges that are known hurdles in this field, and deepened our clinical and preclinical expertise. From our Phase 1-2 Steadfast Study of TX200 for the prevention of immune-mediated rejection in HLA-A2 mismatched kidney transplantation, we have now dosed four patients, including the first patient in the second dose cohort. The product candidate continues to be well tolerated for all treated patients today, and we're encouraged by the early translational medicine data emerging from this study. This quarter, we also received approval for an accelerated dose escalation protocol that will allow us to advance significantly more quickly through the dose cohorts and which adds a new fourth dose level to the protocol. We've already successfully manufactured a dose for patient in cohort three and for the first patient in cohort four. These patients are enrolled, manufactured, and we know when they'll be dosed. And we expect to dose the first patient in this highest dose cohort in January, a meaningful year and a half earlier than originally planned. Acceleration to this top dose level, which is 18-fold higher than the starting dose, could allow potential partners or investors to view efficacy as early as early next year. While the progress being made in the clinical program is exciting, the real value of this business is in what lies beyond the proof of concept with TX200. We believe this technology is ideally suited to treat autoimmune conditions with high unmet medical need and significant commercial opportunities. And our preclinical work in multiple sclerosis and inflammatory bowel disease supports that potential. We have received external interest seeking ways to invest specifically in our CAR T reg pipeline. and have therefore been in active discussions with parties to explore ways that they can do so. We have shared initial TX200 data with the potential investors and will continue discussions in an effort to realise the true potential of this exciting science. If we are not successful in closing collaboration or financing transactions over the coming months, we will consider other alternatives for our CAR-T reg cell therapy programmes. And we plan to provide an update on these efforts at the beginning of next year. In the meantime, we've decided to defer new investments until we're able to successfully secure a collaboration partner or external investment. We believe that discontinuing spending beyond our current commitments while seeking potential partners and investors for both Fabry and CAR Tregs that are both better suited to develop each technology and have the resources needed to bring them to patients will also allow the market to better assess each business's value. As a result of all I have outlined today, we're announcing a reduction in our current US workforce. We also expect to close our Brisbane, California facility in early 2024 to conserve cash resources, and we'll transition our headquarters to our Richmond, California facility as of January 1st, 2024. Point Richmond is the original home of Zankamun where Zinkfinger editing and CAPSID development capabilities are based. These actions are designed to focus our cash resources in advancing our Zinkfinger platform and our CAPSID discovery engine. We believe these changes in combination with the cost savings expect from the restructuring, workforce reduction and other potential cost reduction initiatives will reduce our annual operating expenses by approximately 50% and allow us to fund our planned operations into the third quarter of 2024, assuming no other additional capital is raised. Alongside these announcements, and with real personal sadness, I share that Mark McClung, Executive Vice President and Chief Operating Officer, will also be leaving the company. In the context of a streamlined and more focused organisation, Mark and I felt it was important to align the leadership team with the changes being announced. I've known Mark for many years and have an enormous respect for his wisdom, judgment, and leadership. All of us have benefited from his business experience and constant reminder to focus on the patient. A trusted, confident, and colleague, he'll be enormously missed. Until his departure, Mark will continue to lead our search for partners and investors in our Fabry and CAR T-REC programs. Jason Fontenot, Senior Vice President and Chief Scientific Officer, will also be leaving the company. Jason's scientific expertise is well known in the industry. We have been lucky to have him guide our CAR-T reg and broader scientific efforts. He leaves a strong scientific legacy for which we will always be grateful. With our clear focus on neurology at the corner shown to Sangamo going forward, I'm pleased to welcome Amy Puller, Head of Research, and Greg Davis, our current Vice President of Genome engineering, design and technology as Sangamo's new head of technology. These roles will be critical as we continue to advance our neurology focused pipeline and continue to innovate in the potential life changing field of research. I look forward to having them both join the leadership team. These decisions were not made lightly, and it's incredibly hard to let go of such talented team members who've dedicated themselves to advancing our mission. However, we recognize in order to move forward and to protect our future, we must become a leaner, simpler organization focused on progressing our neurology programs with a simplified and purposeful capital allocation and in turn, increased flexibility to grow. We are committed to aligning our investment strategies to our goals going forward, which are more focused than ever. I believe in Sangamo. I believe in Sangamo as a standalone neurology-focused genomic medicine company, with our core pipeline and outlicensing opportunities as the foundation of our business model going forward. Through our neurology business, we aspire to apply our differentiated epigenetic editing capabilities and our novel engineered capsids to revolutionize the treatment of neurological disorders. Sangamo has both the differentiated genome-targeted cargo and the delivery capabilities of the capsid to be positioned favorably versus others in the field. The data we have shared for our NAV1.7 and prion disease programs provide promise for our program going forward. And we have encouraging data from other advanced preclinical programs, including tau for Alzheimer's disease and alpha-synuclein for Parkinson's disease, which were progressed extensively as part of prior collaborations. And we had simply paused pending the identification of a suitable delivery capsid. We believe we have made meaningful progress in identifying such a blood-brain barrier penetrant capsid through the work with our sifter platform. which we believe will open the door for many other high-value and unmet diseases that can be addressed uniquely with our editing capabilities. The neurology-focused genomic engineering business is the future of Sangamo and is the culmination of a strategy that has been in the works for some time because of the compelling focus business model it represents and the potential commercial opportunities we believe it affords. We are excited about the opportunities that lie ahead. Opportunities are best for patients, best for advancing our science, and best for the shareholders who have stayed with us through this journey. I'd now like to turn the call over to our new head of research, Amy, to discuss the strategy of our neurology program in more detail. Welcome, Amy.

Thank you, Sandy, and good morning, everyone. As you've heard today, we are on a journey to transforming Sangamo into a pure play neurology genomic medicine company committed to driving forward development of potential treatments for neurological disorders in order to better serve patients. I'll go into more detail on the value we see in this business and the strategy behind our neurology programs. At a high level, we have a differentiated platform that can create powerful genomic medicine, a powerful genome targeting cargo with preclinical data that demonstrates the potency, specificity, and importantly, the efficacy we may be able to achieve. Our technology allows us to target neurological indications in the most direct and genetically validated way. In defining our pipeline and pathway forward, we choose to focus on indications where there is a clear driver of disease. Not only do we believe this strengthens the likelihood of preclinical success, but we also believe it increases the speed to potential approval. Because the drivers of disease are well understood, meaning we know which genes cause the diseases, we're able to effectively target those genes that offer curative potential. Pursuing the fundamental drivers of disease is, in our view, a very compelling approach. Sangamo has highly differentiated technology that we believe allows us to execute on our strategy. We're developing proprietary genome-targeting cargo as well as our own novel delivery capsids, whereas most other companies are really doing one or the other. The favorable AV compatibility of zinc finger proteins over other editing modalities has enabled Sangamo to lead the field in neurological medicine development using a range of approaches, including epigenetic gene repression, activation, and multiplexed approaches. This gives us both a competitive advantage as we progress our neurology pipeline and presents future opportunities for partnerships. It's important to understand that in genomic medicine, the drug consists of the cargo, the delivery capsid, and the promoter, which enables tissue-specific expression of this cargo. This trilogy is what becomes a treatment for patients with genetic diseases. And the strength that we have as a company in this space lies in our control over all three of these components. We believe this provides a strong foundation for the future of Sangamo, given our unique position and ability to lead in the area of epigenetic regulation. As a reminder, zinc fingers possess unique qualities that make them superior to other therapeutic approaches being explored. They're versatile, customizable, allow for genome-wide coverage, and are very compact. And as such, we're pleased to see that zinc fingers are increasingly being recognized in the field for these benefits and being more widely embraced. Our promoters, the zinc finger cargo and novel delivery capsids, are designed to work together to target specific cells and tissues and optimize efficacy and safety. We're able to powerfully control the repression or activation of genes, a benefit not necessarily shared by other therapeutic approaches. The favorable safety profile comes from the specificity we're able to achieve, coupled with the fact that zinc fingers are human-derived, reducing issues related to immunogenicity. Moving now to our pipeline, which leverages the delivery capabilities we currently have in hand in combination with our zinc finger technology. Our neurology pipeline is led by NAV1.7, which leverages the exquisite specificity of zinc fingers to repress a target that has been challenging for other technologies. In addition, we believe this program is important because of the broad population we can address in small fiber neuralgia, an intractable pain syndrome that dominates the lives of these patients, plus the future opportunity to expand into other related indications. We continue to advance this preclinical program and continue to anticipate an IND submission in 2024. We have also defined prion disease as another important program in the pipeline where we will implement our epigenetic regulation technology using a blood-brain barrier crossing capsid. Beyond these programs, we strongly believe we have the capsid engineering capabilities needed to expand delivery beyond our currently available intrathecal delivery capsids. The industry broadly is challenged with finding or developing a capsid that can cross the blood-brain barrier. We are making excellent progress identifying potentially effective intravenously delivered AAV capsids to transport these cargo into previously untouched areas of the nervous system and hope to share results from the non-human primate studies in early 2024. Unlocking blood-brain barrier penetrant delivery mechanisms would be transformative for our neurology pipeline, opening up significant untapped indications to development and releasing significant potential for additional sanguinal partnerships. Some of the high-value targets we could advance include tau and alpha-synuclein, which we deprioritized solely because the capsid was not available at that time. Sangamo has the technology and strategy around which we are building a focused neurology company, developing all components of potential genomic medicine and engineering medicines. The data we've generated makes us confident in our ability to be leaders in the space, and I look forward to providing updates in the upcoming quarters. I will now turn the call over to our Chief Financial Officer, Pratusha, for an overview of the financials. Pratusha?

Thank you, Amy, and good morning. Over the course of 2023, we have proactively made difficult decisions to preserve our most valuable assets. The public biotech markets have been challenging for over two years now, and we find ourselves in a similar position to many of our peers with limited capital resources and a tough path to navigate ahead. This has necessitated the exploration of our strategy execution and the focus of spending in line with our mission as a neurology-focused genomic medicine company. As Sandy outlined earlier, this means optimizing our resources and continuing our efforts in seeking investment alternatives for Fabry and T-Rex. Furthermore, as part of streamlining our spend, we expect to exit our Brisbane, California facility in early 2024. We will be scaling back our internal manufacturing capabilities and leveraging external partners to manufacture clinical supply for our neurology pipelines. These actions have resulted in a reduction of approximately 162 roles or 40% of our US workforce. The annual cost savings resulting from the workforce reduction combined with other potential cost reductions is expected to reduce our annual operating and will non-GAAP operating expenses from 240 to 260 million this year to around 150 to 135 million in 2024. a decrease of approximately 50% year-over-year. We ended the third quarter with approximately 132 million in available cash, cash equivalents, and marketable securities. We believe that these resources, in combination with the cost savings expected from the restructuring and other potential cost reductions, will be sufficient to fund our planned operations into the third quarter of 2024 without factoring in any additional capital raises. We continue to accumulate important Phase I-II data in the Fabry disease and TX200 while we seek solutions to unlock the value within these programs, which could generate valuable capital for our neurology epigenetic regulation pipeline. Additionally, we continue to evaluate several avenues to raise capital and hope to have an update in the next few months. As a reminder, Pfizer continues to work towards a pivotal readout in mid-2024 in a hemophilia A collaboration and anticipates potential BLA and MAA submissions in the second half of next year. This partnership agreement allows for potential milestones of up to $220 million and 14% to 20% in royalties, which could be a significant source of funds starting as early as the end of next year. We expect our 2024 operating expenses for the core neurology company to be in the range of 80 to 100 million. This range excludes additional transition costs of approximately 30 to 40 million in 2024 as we complete our strategic transformation, which are expected to significantly decrease in the future years. We will provide official 2024 non-GAAP operating expense guidance as part of our fourth quarter update. I will now turn the call back to Sandy for closing your mouth.

Thank you, Prathusha. As you've heard today, Sango continues to advance our transformation to becoming a neurology-focused genomic medicine company. This has been in progress since 2020. Against a challenging backdrop, we've needed to make incredibly hard decisions for our employees and our programs and developments. In the coming months, we'll continue to work diligently to unlock value from our Fabry and CAR-T reg programs and to drive forward our neurology pipeline. We will provide updates on these processes when appropriate to do so. Thank you again to those very talented individuals, to these friends and colleagues who will be leaving Sangamo. Your tireless efforts and dedication have helped to progress Sangamo's science and support the organisation and for that I am very grateful and I wish you the very best in your next chapters. As I look to the future, I'm excited about the opportunities that lie ahead. We'll progressively share more data and news from our neurology programmes and anticipate sharing non-human primate data showing our progress identifying new novel delivery capsids early next year. The team continues to generate more preclinical data for NAF 1.7 and has initiated final IND enabling studies, and so is progressing towards an expected IND submission in 2024. We are still anticipating the pivotal readout for Haemophilia A in mid-24, with the first valuable milestone potentially coming as early as next year. As we work to raise additional capital, we hope to announce an update in the coming months. I am very thankful to our leadership team and all my Sangamore colleagues for their hard work and dedication to our mission. I'd like to close by expressing my hope and excitement for the future, a future that lies ahead for Sangamore and as a focused genomic medicine neurology company. At this time, we'd like to open it up for questions. Operator, please open the line for questions.

Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. The first question comes from Reena Patel with RBC Capital Markets. Your line is open.

Hi. Thanks so much for taking my question. This is Reena. I just wanted to ask, would you be able to kind of walk us through what would be an ideal partner and ideal structure for the Fabry program partnership?

Good morning. Thank you. Thank you for your question. So you're asking, what does an ideal partner look like for Fabry? Mark, you've spent a lot of time working on this.

So I think, you know, from our standpoint, the partner would be someone that has a commitment to the patients with Fabry disease and sees the pathway that we've agreed with the agency and has the capital resources to ensure that the study gets completed in a timely manner and commercialized globally to these patients. And there are a number of companies that fit that. and we'll provide updates when we finish conversations with them.

Please stand by.

Okay.

Please stand by for the next question. The next question comes from Andreas Argyrides with Wedbush. Your line is open.

Good morning. Thanks for taking our questions. Two from us here and kind of a follow-up to the last one. So just understanding capital constraints and the need to extend the cash runway. Fabry is the most advanced program and there's good data to date. Can you also provide us an update on the phase three design if there were any updates and you were in discussions with the regulatory agencies there? And then we noticed that Biogen had been selling a majority of their shares. If you could provide any color around that, that'd be helpful as well. Thank you.

Thank you for your question. So let me do the first one, the one about Fabry. And I'm going to ask Natalie to help us think about the design of the phase three. I just want to reiterate what I said in the script. The results in Fabry are, I think, the most compelling of any clinical program I've worked on in 25 years. It's a holistic benefit from the patient. And patients literally came up to us at the recent Fabry meeting and said, I have your gene inside of me and I've never felt better. My life has been transformed by that. And that's why, as Mark says, finding a company that can take this into phase three globally is so important. Natalie, how are we doing with thinking about the phase three?

So, you know, we were pleased to share last quarter the clarity we received from the agency on our proposed naive and pseudonaive study design. We continue to have productive conversation with the FDA and really are a good place on potential phase three plans that can be activated in the future. We also received RMAT vaccination recently from the U.S. FDA, which really is a recognition that this potential medicine addressed significant unmet needs for Fabry patient population, but also it signaled that the data produced so far has been highly encouraging And those, the RMAT designation really provide the opportunity to have live conversation with the FDA. So we're very pleased that we will be in a very good position for any potential partner to start our phase three program.

Thank you, Natalie. And Patricia, can you comment on the shear cell?

Sure, Sandy. Your question on the biogen cell. As you know, Biogen's main business is like us, getting medicines to patients. It's not really in the business of holding equity with other companies. So our understanding is their main intention of this sale was to get under the 10% threshold, and we're not expecting any future sales at this point.

Thank you. Thank you, guys. Thank you.

Please stand by for the next question. The next question comes from Maury Raycroft with Jefferies. Your line is open.

Hi, this is Kevin Strang on for Maury. Thanks for taking our questions. Just wanted to, you already touched on sort of the Fabry phase three, where you left off with talks with the FDA, but I wanted to switch over to CAR Treg for that program. Can you talk about what went into your decision to not show cohort one data by the end of the year? Is that basically because you're getting to a potential efficacious dose earlier than you originally thought? And then can you say whether or not you looked at any of the renal biopsy data and then saw evidence of presence or expansion of Tregs or any commentary you can share on safety so far?

Good morning. Yes, thank you. And you're spot on with why we are delaying showing the data. Originally, the study design was three patients per cohort and then an SMC and then another three patients. And with the complication of running a study in renal transplant, that was driving the top dose way out into 25 patients. With our really novel clinical design from the clinical team, they've managed to bring this in much quicker with a Bayesian design. And we will have those patients in the top dose as early as January of next year. Therefore, we'll have a package of data that we can share next year rather than dribbling it out cohort by cohort. And I'm sure you will agree that makes your job a lot easier. As to what we've seen so far, we've dosed three patients in cohort one and one patient in cohort two. And Natalie, they're doing extremely well, aren't they?

Yeah, the safety of the product has been demonstrated for those two cohort. We have also, in addition, added a fourth cohort to our new design, which is a dose that is 18-fold higher than the dose in cohort one. So we're very excited about this. a manufacturer capability for the TREC platform.

And we're very careful to say, to hold off showing all the data until next year. We encourage what we've seen so far, but really what will be most compelling would be if we show you all those levels and for a larger group of patients. So we look forward to doing that next year. Great. Thank you.

Please stand by for the next question. The next question comes from Nicole Germino with Truist. Your line is open.

Hi, this is Nishant. I'm on for Nicole. Thanks for taking our questions. Maybe talk a little bit about your efforts focusing on epigenetic regulation therapies, which you're focusing on now, neurological disease and novel capsids. Is this an area of greater pharma beauty interest, and is that why you're focusing on it?

So I'm going to pass this over in a moment to Amy to say why neuro is particularly good for our form of regulation. Our decision is a very chosen one. And it's, as I said, we've been on this journey internally for three years. Neurological diseases are an enormous burden to society. And we feel that this fits with our long-standing technologies and allows us to make a difference. Amy, why do the zinc fingers work particularly well in this field?

Thanks, Sandy. We believe that the approach using the zinc fingers gives us really an unprecedented opportunity to regulate gene expression in the brain and match it specifically to the neurological disease indications. Being able to precisely and specifically up-regulate or down-regulate genes that are involved in these really challenging neurological diseases gives a new opportunity to treat those diseases. In addition, because the zinc fingers are so small, they package very easily into AAV capsids. And that gives us another chance to not only design the cargo, but to design the delivery vessel that will bring them to the areas of the brain or the areas of the nervous system where they can have the biggest impact in modifying the disease progression. So those things together, the cargo of the zinc fingers plus the capsids that are able to deliver to these specific brain regions, we think will make a really transformative impact into these neurological diseases.

Amy, others are using ASOs that they have to inject often or inject intrathecally. Why will ours be once and done?

That's right. Because neurons and other brain cells are usually terminally differentiated, it means that we predict that the expression of the zinc fingers will be durable and last the lifetime of the patient. This is what we believe will be the case, and we look forward to showing that in the clinic. But it does mean we have a one and done approach. Thank you.

Please stand by for the next question. The next question comes from Patrick Pruccio with HC Wainwright. Your line is open.

Hi, everyone. Thank you for taking the call. This is Luis for Patrick. I'd just like to ask about the newer programs that you still have going on for Alzheimer's with tau and Parkinson's with alpha-synuclein. You said you've announced previously you have increased penetration with the brain capsids, so You're going to prioritize these programs now. When are we going to see more data from them?

Amy, can you talk about where we are with tau? Because there's been interesting data on tau recently, hasn't there?

Yeah, absolutely. I mean, with our previous partnership, we're able to progress that program quite a long ways. We have our clinical lead, ThinkFinger, which has really been able to show some potent and specific repression of tau in the brains of our preclinical models. And we look forward to pairing that in future potentially with a blood-brain barrier capsid that would enable delivery across the nervous system.

And the results of those have shown in tau gives us reasons to believe in this as a target.

Yeah, absolutely. It's really been some fantastic data that's coming out in the field now showing that specific reduction of tau is able to remove some of the neurofibrillary tangles or some of the pathology that's related to tau. So we think that that gives even more evidence that a tau-targeted approach could be critical for treating something like Alzheimer's disease, but also other tauopathies.

Thank you.

As a reminder, to ask a question, please press star 11 on your telephone. Please stand by for the next question. The next question comes from Nanyan Zhu with Wells Fargo Securities. Your line is open.

Hi, thanks for taking our question. This is Kuan Ang for Yanan. So first question on TX200. I wonder, even though it's only like two cohorts, but I wonder if you have seen any dose response and any immunosuppressant tapering, and what are the potential partners might be looking for?

Thank you. So there's two parts to that question. We've only dosed one patient in cohort two, and they were only recently dosed. So it would not be possible to know if there's any benefit, nor have they started any process of tapering. As I said, it's going to be so much more rich data set to show you the whole package next year. What are partners looking for? There are Many CAR Treg companies, I think I count over 10 of them, and they've all been funded and founded on preclinical promise. And Sangam was like the field here, and we're the only patient, the only one that has publicly said we're in the clinic. And the fact that we've shown that we can dose four patients with CAR Tregs and it is safe, I think is a really important thing for the whole field. the first time the T regulatory cell has been engineered and put into patients. We go from cohort one to cohort four and it increases 18 fold. So we have a great range of amount of cells to add and we look forward to showing you that data next year.

Got it. Thank you. And on the AAV capsid, can you share what are you hoping to show or to achieve

in nhp assuming that that would be in the first quarter next year data amy what do people look for in nhps and what does good look like thanks denny i'm so excited really about the work that's being progressed by our capsid evolution group and these capsids are essential really for delivering the genomic medicines to to the right place in the nervous system And all of the engineering work that goes into solving these challenges that the brain has kind of thrown up at us, but that it's critical to engineer that so that we're able to deliver the medicine. We're looking for capsids that are able to deliver the zinc finger cargo broadly across the brain into brain regions that we know are involved in these neurological diseases that we're targeting. And we're able to do that using our preclinical models and try to understand how that will work into patients. You know, we're unique in the company, really. You know, that's just why I'm so excited about this work, because we have the outstanding Syncfinger platform, but also these capsid delivery efforts that will allow us to create the medicines, as I talked about before, that are really bringing together those components. And we're definitely looking forward to sharing more about that early next year.

So it's about expression of the caps that drive the brain. It's about the activity of the zinc finger. And it's about consistency in areas that are clinically relevant. That's what good will look like.

Absolutely. Yeah, absolutely. Got it. And that's one from me. So on the human program, any comments on the potential of monetizing the royalty?

Thank you. So... We can't really comment on any financing or monetization efforts. But, Natalie, we really feel that Pfizer are doing a good job here, don't we?

Yes. All the patients in the pivotal trial have been dosed. And really, the Pfizer is still guiding to a pivotal readout expected in mid-2024 and submission of a BLA and MA in the second half of 2024. As you know, you know, hemophilia as a whole is a big area for Pfizer, and they have all the workforce to be able to advance this very efficiently into the market. So we're very encouraged, and we have regular call with our Pfizer colleague, and the momentum is palpable.

I know you'll want to hear more about it. Pfizer, every signal Pfizer are giving us are positive that they believe this is an important program for them. As regards the monetization of the royalties, if we monetize it now before the results are out, it would be an extremely discounted rate. The longer we can wait before monetizing it, the better and the more valuable it will be. keeping it going all the way to the royalties and milestones coming directly to us would even be more valuable. And so it's just a decision that Prathusha and I have to make as we finance the company.

Got it. That's helpful. Thanks for all the color.

I show no further questions at this time. I would now like to turn the call back to Reese Wilkie for closing remarks.

Thank you. And once again, thanks to everyone 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 Sangoma website. We look forward to keeping you updated on our future developments.

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