Q1 2023 Sangamo Therapeutics Inc Earnings Call
Speaker 1: You you F.
Operator: Good day, and thank you for standing by. Welcome to the Sangamo of first quarter, 2003, 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 1-1 on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press Star 1-1 again. 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. Go ahead.
Speaker 2: Good day and thank you for standing by. Welcome to the Sangamo of first 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.
Speaker 2: You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star 1-1 again. 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: Thank you. Good morning.
Louise Wilkie: I'm Louise Wilkie, Fangermost'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, Patricia Dura Babou, Chief Financial Officer, Jason Fontnoe, Chief Scientific Officer, Natalie Dubois Stringfellow, Chief Development Officer, and Bettina Cockcroft, Chief Medical Officer. Slides from our corporate presentation can be found on our website, Sangamow.com, under the Investors and Media section of the events and presentations page.
Speaker 3: 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 McCrae, Chief Executive Officer, Mark McClung, Chief Operating Officer.
Speaker 3: producer duo barbeque chief financial officer Jason Fontneau chief scientific officer Natalie Dubois Ring fellow chief development officer and patina cop cross chief medical officer
Louise Wilkie: This call includes forward-looking statements regarding Sangamo's current expectations. These statements include, but are not limited to, statements related to the therapeutic and commercial potential of our product candidates, the anticipated plans and timelines of Sangamo and our collaborators for initiating and conducting clinical trials, screening, and voting patients, and presenting clinical data. Advancements in our product candidates, advancement of preclinical programs to the clinic, our strategic reprioritization and restructuring and the anticipated benefits thereof, a sufficiency of our resources, cash runway, and plans to seek additional capital.
Speaker 3: Slide to my corporate presentation can be found at our website, Sangamo.com, under the investors and media section of the events and presentation page.
Speaker 3: This call includes forward-looking statements regarding Sangamo's current expectations. These statements include, but are not limited to, statements related to the therapeutic and commercial potential of our product candidates, the anticipated plans and timelines of Sangamo and our collaborators for initiating and conducting clinical trials, screening and dosing patients and presenting clinical data, advancement of our product candidates.
Speaker 3: Advancement of pre-clinical programmes to the clinic. Our strategic reprioritisation 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.
Louise Wilkie: Our preliminary estimated operating results for the 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. However, actual results may differ materially from what we discussed today. These subject statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC, specifically in our annual report on Form 10K for the fiscal year ended December 31, 2022, that will be supplemented by our quarterly report on Form 10 for the quarter-ended March 31, 2020, to be filed with the SEC.
Speaker 3: 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 .
Louise Wilkie: The forward-looking statements stated today are made as of the state, and we undertake no duty to update such information except as required by law. On this call, we discuss our non-gap operating expenses. Reconciliation of this measure to our gap 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, Andy McCrae.
Speaker 3: for the quarter ended March 31, 2023 to be filed with the SEC.
Speaker 3: The forward-looking statements stated today are made out of this date and we undertake no duty to update such information except as required by law.
Speaker 3: On this call we discuss our non-GAAP operating expenses. Reconciliation of this measure to our GAAP operating expenses can be found on 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: Thank you, Louise, and good morning to everyone joining the call. As I reflect on where Sangam is today, I'm proud of a rich history of scientific innovation and industry firsts. We are committed to developing genomic medicines that have the potential to transform the lives of patients and to bring value for shareholders. In so doing, we've been driving forward important programs in our pipeline, which are producing promising results. Today, I want to step back and spend some time reiterating the vision for the company and why we believe Sangmo 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 more effectively to achieve that vision.
Speaker 4: Thank you, Louise, and good morning to everyone joining the call.
Speaker 4: As I reflect on where Sangamore is today, I am proud of our rich history of scientific innovation and industry firsts.
Speaker 4: We are committed to developing genomic medicines at the potential to transform the lives of patients and to bring value for shareholders.
Speaker 4: In so doing, we've been driving forward important programs in our pipeline, which are producing promising results.
Speaker 4: Today I want to step back and spend some time reiterating the vision for the company and why we believe Saintville has a potential to create significant value in these areas of chosen focus.
Speaker 4: I will then outline a strategic reorganization that is being announced today to prioritize resources and spend in an effort more effectively to achieve that vision.
Alexander D. Macrae: We will advance our wholly owned neurology portfolio of preclinical assets that leverage the power of our zinc finger epigenetic regulation technology and are underpinned by strong capsid delivery capabilities. Anchored by our newly unveiled NAV-1.7 program for the treatment of chronic neuropathic pain and the Priam program for the treatment of Cruttsville-Yacob disease, we believe these targets are addressable today with existing delivery technology and present both large 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 that has the potential to result in 1 I&D submission a year over the coming years.
Speaker 4: We will advance our wholly owned neurology portfolio of preclinical assets that leverage the power of our sink finger epigenetic regulation technology and are underpin by strong capsid delivery capabilities.
Speaker 4: Anchored by our newly unveiled Nav 1.7 programme for the treatment of chronic neuropathic pain and the PRIMON programme for the treatment of Creutzfeldt-Jakob disease.
Speaker 4: We believe these targets are addressable today with existing delivery technology and present both large unmet medical needs as well as market opportunities.
Speaker 4: 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 one IND submission a year over the coming years.
Alexander D. Macrae: At the same time, we continue to advance our industry-leading Fabry and TX200 CARTREG clinical programs, both of which have the potential to provide significant benefit to patients and value to shareholders. We are leading gene therapy and development to treat Fabri disease.
Speaker 4: At the same time, we continue to advance our industry-leading Fabry and TX200 CAR-T Reg clinical programs.
Speaker 4: both of which have the potential to provide significant benefit to patients and value to shareholders. We are leading gene therapy and development to treat Fabry disease. With competitors continuing to announce the pausing or termination of programs, we believe Sangamo is ideally placed to address the needs of this important patient population.
Alexander D. Macrae: With competitors continuing to announce the pausing or termination of programs, we believe Sangamu is ideally placed to address the needs of this important patient population. The promising safety and efficacy data we've presented today reinforces the potential of this program, and we're making good progress in preparations to consult the FDA on the proposed phase three trial design in the summer, once we have the data needed to support these conversations. Sangamol is also a leader in the CAR-T-Reg cell therapy space, being the only known company to have those patients in a clinical trial through our TX-200 Steadfast Study. We believe renal transplantation is the ideal model for a CAR-TREG proof of concept.
Speaker 4: Sangabot is also a leader in the CAR Treg cell therapy space, being the only known company to dose patients in a clinical trial through our TX200 steadfast study.
Alexander D. Macrae: And if safety and efficacy are adequately demonstrated, CAR-T-Regs could be well suited to treat a broad range of autoimmune indications, holding great promise and new treatment modality. We believe that our advanced T-R&D capabilities, coupled with our manufacturing know-how, place us in an ideal position to continue to be a leader in the CART-Reg cell therapy field. To date, we have seen signs of success in more assets than the company can take forward on a loan, which is a very rare position for a company in this industry to be in.
Speaker 4: of consent. And if safety and nettoxycy are adequately demonstrated, CARTY rights could be well suited to treat a broad range of bottom-union indications, holding great promises and new treatment modernity.
Speaker 4: We believe that our advanced T-reg R&D capabilities coupled with our manufacturing know-how places us in an ideal position to continue to be a leader in the car T-reg cell therapy field.
Speaker 4: 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.
Alexander D. Macrae: This requires focus and a disciplined approach to using data to inform what to progress, while also considering the commercial potential of each aspect. While we must focus on progressing the science and delivering for patients, we must also manage a 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 cashbuy.
Speaker 4: While we must focus on progressing the science and delivering for patients,
Speaker 4: We must also manage a 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.
Alexander D. Macrae: We're 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, we're announcing a sharp and strategic focus. With investments being carefully prioritised to advance three key areas, one, our newly unveiled NAV1.7 and prime programs as our prioritised wholly own neurology portfolio, 2, our Fabri program to a potential phase three clinical trial, and three, the TX200 CAR2 reg program in renal transplant through phase 1,2. We believe these are the core value drivers for the business.
Alexander D. Macrae: With the upcoming return of the programs from Bayesian Novartas set within the wider economic backdrop, we've had to carefully select which neurology programs to take forward, while also re-evaluating how we resource our strategic priorities. We have prioritized specific neurological epigenetic regulation targets that we believe can be delivered today through existing capsids, highlighting the importance of our capsid evolution program to drive future value for the company, and are advancing these programs to potential I&D.
Alexander D. Macrae: This has led to difficult but necessary decisions to step away from some preclinical assets, as well as significantly reducing our internal manufacturing and allergenate research footprints in California. We recognize internal manufacturing, especially in California, is an expensive and resource intensive activity.
Alexander D. Macrae: So at this time, we believe our spend should be focused on clinical and pre-clinical activities, which we expect to drive value in the near term. We are therefore announcing today the elimination of approximately 120 roles at San Gamow in the US, representing 27% of the current US workforce. The restructuring plans, plus other planned cost reduction initiatives, are expected to result in annualized savings of approximately 31 million dollars.
Alexander D. Macrae: 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 prioritized objectives and the progress of the company. Alongside these announcements, and with real personal sadness, I share that Andy Ramomar, Executive Vice President of Technical Operations, will be leaving the company. Andy has brought great passion and dedication to Sangu.
Alexander D. Macrae: Building a manufacturing organization has allowed us to support the advancement of more 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 Sangamon. Billet Ramsey, our current head of technical development, has been appointed to serve as a head of technical operations effective May 29th. I really look forward to working with Billie 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.
Alexander D. Macrae: 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. 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.
Alexander D. Macrae: 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 D. Fontenot: 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 results 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.
Jason D. Fontenot: By focusing on advancing our prioritized neurology portfolio, Fabri, to phase three, and our TX200 CARTREG clinical study through phase one and two, 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 Sangamos proprietary zinc finger gene targeting technology, a high-precision genomic engineering platform. It is highly versatile, extremely customizable, and very compact.
Jason D. Fontenot: Once delivered, our epigenetic transcriptional regulators are capable of repressing or activating the expression of target genes for therapeutic benefit without the introduction of mutations, breaks, or other permanent changes to the genome. Thus, they are well suited to address neurological disease.
Jason D. Fontenot: 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, such as existing AAB caps. We are currently 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 I&D submission a year over the next few years.
Jason D. Fontenot: Today, we unveiled a flagship program of our Holiology Pipeline, Nav 1.7. Using an optimized zinc finger epigenetic repressor, 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 manipulation 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's most closely related receptors.
Jason D. Fontenot: Our initial focus will be Nav 1.7 associated small fiber neurologica, with an estimated prevalence of at least 43,000 patients in the U.S. We believe we can specifically prevent the transmission of noosiceptive 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, regardless of the cause of pain. Importantly, reducing pain by inhibiting NAB 1.7 is not known to be associated with any other neurological side effects, and other sensory modalities are not expected to be affected.
Jason D. Fontenot: Detailed preclinical data from this program will be shared via a platform presentation on May 17th at the upcoming American Association of Gene and Cell Therapy annual meeting in Los Angeles. We are anticipating an I&D submission for the NAV 1.7 program in 2024. Beyond Nav 1.7, we continue to advance our wholly-owned neurology program targeting the preon protein for the treatment of Kreuzfeld-Yakup disease. At the Preon 2020 conference last September, we presented data demonstrating that our approach to targeting neurological pathologies with zinc finger repressers is effective.
Jason D. Fontenot: Our prion targeted therapy reduced the expression of preon by 40 to 60% in the brains of mice, reducing toxic preon aggregates that drive neuronal degeneration. This data, developed in collaboration with the Massachusetts Institute of Technology's Broad Institute, demonstrated that the therapeutic administration of our zinc finger epigenetic compressors significantly extended survival of preon-infected mice through to 500 days, the typical lifespan of these mice. Importantly, the effect was superior to published ASO treatment.
Jason D. Fontenot: This data provides validation of our work in Preon disease, but more importantly for our entire neurology-targeted zinc finger epigenetic repressor portfolio. Preon 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 the onset of illness.
Jason D. Fontenot: Our intent is to target symptomatic, hereditary, sporadic, or acquired Croixville-Jacobs 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 Preon program, with a potential I&D submission expected in 2025. Delivery to the central nervous system is a major hurdle for the clinical application of genomic medicine. The blood-brain barrier limits the brain-wide distribution of intravenously administered macromolecules.
Jason D. Fontenot: To overcome this issue, we have developed a proprietary AAB Capsid Discovery platform called Sifter. Sifter allows us to engineer AV CAPs, 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 AAB caps, 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 it will also provide valuable revenue generation opportunities through potential partnerships.
Jason D. Fontenot: I'm very pleased with the progress we have made and look forward to sharing more about our AB capsids in the near future. With regard to our partner neurology programs, we received notice this quarter that both Biogen and Avortis have decided to terminate collaborations with us. While completely unrelated, these two decisions had an unfortunate, coincidental timing coming in the same week.
Jason D. Fontenot: 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 firms to step away from early stage risk and prioritize investment in de-risk, late-stage, and commercial products. While we understand these decisions, Sangmo's focus is bold discovery to create transformational medicine. However, Informa, such work is out of favor as companies look for cost savings.
Jason D. Fontenot: 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 activity.
Mark McClung: 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 AAB capsids to facilitate the delivery necessary for success in these indications. Notably, the programs returned to us from Biogen and Navarre 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. Thank you, Jason, and good morning, everyone.
We know that there are approximately 4000 diagnosed fabry patients in the United States as well as many more that are not diagnosed even with family <unk> incidents of the disease.
Those diagnosed around 13 to 1900 are actively on treatment like enzyme replacement therapy, although many struggle with it adherence to the regiment.
Mark McClung: Starting with Fabri, 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 Fabri disease. As we actively prepare for a potential phase three trial, it's helpful to remind everyone of the market opportunity for this asset. We know that there are approximately 4,000 diagnosed Fabri patients in the United States, as well as many more that are not diagnosed, even with familial incidents of the disease. Of those diagnosed, around 13 to 19, are actively on treatment like enzyme replacement, although many struggle with adherence to the regimen.
We have successfully recruited naive pseudo naive patients into our phase one to study as well as patients already on E. R T, which demonstrates the designer of patients to have alternative and improve treatment options over and above the standard of care.
We will therefore continue to appropriately invest in this program to maximize the chances with 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 Mark biomarker data to kidney biopsies and improved S. F 36 General health scores.
Since Q for earnings we have dose to further three patients in the phase one to study to achieve a total of 20 patients to date.
And we continue to enroll in this study.
We strongly believe S. T 920, as a potential medicine. So we're progressing phase three planning with urgency.
Mark McClung: We have successfully recruited naive and pseudo-naive 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 on kidney biopsies and improved SF-36 general health scores.
And plan to meet with the F. D. A on the proposed study design. This summer once we've accrued sufficient data for those discussions.
Trials 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 one two for which we expect to complete dosing in 2023 is not expect it to be a gating factor for the commencement of the phase III, but will provide additional data.
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Mark McClung: 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 patients. We strongly believe ST920 is a potential medicine, so we're progressing phase three 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. Trials are 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 regulatory interactions.
When we acquired checks Allen 2018 regained deep expertise and regulatory T cell biology, and married that with our detailed understanding of manufacturing and our experienced developing ind's and progressing programs into clinical development.
With these factors combined we believe we are well placed to maximize the opportunity for car T regs to treat a range of auto immune indications and our <unk> pioneering a new type of treatment modality.
The first of the programs T X 200, and H O a a two mismatched kidney transplantation continues to move through the clinic.
This quarter, we dose the third patient and 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 and pre screening who continue to enroll.
Mark McClung: As a reminder, the expansion phase one and two, for which we expect to complete dosing in 2023, is not expected to be a gating factor for the commencement of phase three but will provide additional data to support the regulatory package. Now turning to our CARTREG portfolio, where once again, we're a leader in the 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 I&Ds and progressing programs into clinical development.
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 are required for the enhance trial design that will accelerate dose escalation. We're also on track to share clinical data from <unk>.
Four one by the end of 2023.
That's part of our sharp and focused we plan to prioritize the investment of our near term autologous Carty ranked portfolio and this has resulted in a decision to transition all allogeneic research activities from the United States tour available on available on France facility.
Mark McClung: With these factors combined, we believe we are well placed to maximize the opportunity for CARTRAGs to treat a range of autoimmune indications and are pioneering a new type of treatment modality. The first of the programs, TX-200, and HLA A2 mismatch kidney transplantation, continues to move through the clinic.
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Well allogeneic capabilities will be important too long term development of the car to your Reg platform. It's important that our resources are directed towards advancing T X 200 at this time.
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Finally, I want to reiterate two other important components of the story that we expect to be valued drivers for the company.
Prathyusha Duraibabu: This quarter, we dosed the third patient in cohort one, and all patients continue to do well. Preparation for the second and higher dose cohorts 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.
The first is Gerard <unk>, an investigational gene therapy, we're developing with Pfizer for patients with moderately severe to severe hemophilia a currently in phase three.
Dosing is complete for all patients required to complete the primary analysis and Pfizer continues to work toward a pivotal rito <unk>.
Expect it in mid 2024.
Pfizer anticipates, the potential B L. A and M M eight submissions and the second half of 2024, which if completed would generate a significant milestone payments. As a reminder, this partnership agreement allows for a potential milestones of up to $240 million and up to 14 to 20 per cent and potential royalties.
Prathyusha Duraibabu: We're also on track to share clinical data from cohort 1 by the end of 2023. As part of our sharpened focus, we plan to prioritize the investment of our near-term atollogous CARTREG portfolio, and this has resulted in a decision to transition all allogenicic research activities from the United States to our Valban France facility, to cease cell manufacturing in our Brisbane, California, While alligenic capabilities will be important to the long-term development of the CART-Reg platform, it's important that our resources are directed towards advancing TX-200 at this time.
The other important potential value driver of our portfolios innovative new taps, it's adjacent outlined earlier and which serves as a resource to address the issue of delivery to places like the central nervous nervous system.
We recognize the importance of unleashing the potential of new engineered taxes as enablers of genomic medicine, both for our own programs and those with potential partners and are making significant progress in addressing delivery to arrange a previously inaccessible areas.
We see this as a 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.
Prathyusha Duraibabu: 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 Dirac-Tococene-Pythiparpovac, an investigational gene therapy we are developing with Pfizer for patients with moderately severe to severe hemophilia A, currently in phase three. Dosing is complete for all patients, required to complete the primary analysis, and Pfizer continues to work toward a pivotal redout, expected in mid-24. Pfizer anticipates potential BLA and MMA submissions in the second half of 2024, which, if completed, would generate a significant milestone. As a reminder, this partnership agreement allows for potential milestones of up to 240 million and up to 14 to 20% in the potential world.
I will now I'll turn it over to our Chief Financial Officer, Patricia for an overview of the financial results Patricia.
Thank you Mark and good morning, everyone.
Sangamo notice preliminary first quarter financial results yesterday, as we look towards competing customer a quarter and close and there'll be a procedures, including the evaluation of non-cash charges related impairment of <unk>.
Preliminary results are as follows revenue.
Revenue for the first quarter, and then March 31st 2023, alright estimated to be approximately $158 million compared to $28 million for the same period in 2022, reflecting an increase of $130 million yearly yet.
This was family driven by the written up assets from Biogen, requiring us to activate approximately how long 21 million of non-cash revenue from the related upfront fees.
Prathyusha Duraibabu: The other important potential value driver of our portfolio's 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 capsses as enablers of genomic medicines, both for our own programs and those of 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, Pratusha, for an overview of the financial results.
GAAP operating expenses for the first quarter I estimated to be in the range of hiring 20 million $240 million compared to $70 million for the same period in 2022, reflecting an increase of 47 million to $67 million yearly yet.
This was primarily driven by certain non-cash charges, including goodwill impairment of 38 million and estimated impairment of long lived assets to 20 million.
These impairments I'd driven by several factors, including termination of significant partner agreements noted previously and lower market capitalization similar to what other companies and <unk>.
We ended the quarter with the process to harm 41 million in cash cash equivalents and marketable securities which is expected to fund the company for at least the next 12 months.
Prathyusha Duraibabu: Thank you, Mark, and good morning, everyone. Sangamo announced preliminary first quarter financial results yesterday as we worked towards completing customary quarter and close and review procedures, including the evaluation of non-cash charges related to the impairment of long-lived assets. The preliminary results are as follows. Revenue for the first quarter ending March 31st, 2021, and 2023 is 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 is the person said plan of approximately $66 million from the <unk>.
So at the moment, the headcount reductions announced today in combination with other plan cost reaction I expected to result in annualized savings at approximately $31 million going forward.
We continue to assess ways to further reduce or annual operating expenses and too many sangamo as a highly focused organization driving towards a prior ties to neurology assets Tapie MTX 200.
I said what size of these changes previously announced 20th 23, non-GAAP operating expense guidance range up to $75 million to $295 million is now obsolete.
Prathyusha Duraibabu: This was primarily driven by the return of assets from Briagin, requiring us to accelerate approximately 121 million of non-cash revenue from the related upfront. Total gap 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.
We expect a current estimate for <unk> to be in the range of $240 million to $60 million.
This wayne exclude certain non-cash charges, including estimated could move by down impairment of long lived assets and stock based compensation expense.
Sam was assisting ways to further reduce operating expenses in line with the check.
Prathyusha Duraibabu: in 2022, reflecting an increase of 47 million.
<unk> and the reader turnkey programs will continue to drive efficient and investments in the coming months.
Prathyusha Duraibabu: $47 million to $67 million year over year. This was primarily driven by certain non-cash charges, including a Goodwill impairment of 38 million, and an 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 equivalence, and marketable securities, which is expected to fund the company for at least the next 12 months.
In parallel sang was committed to creating long term value for our shareholders and we will continue to practically and intensively Expo Avenue to wait additional capital, including two partnerships.
I will now turn the call back to send me for closing remarks.
Thank you <unk>.
Today, you have to sign Google 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 be early submission.
Today, we had known start hulio in neurology portfolio centered around enough 1.7, with a 90 submission anticipated in 2024, <unk> innovative zinc finger technology and underpinned by a capsule development capabilities that we believe can provide file you in the near and long term.
Prathyusha Duraibabu: This represents a decline of approximately $66 million from the previous quarter. Furthermore, the headcount reductions announced today, in combination with other plan 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 neurology assets, Fabri, and NTX 200.
Our market, leading papyri program advances towards a potential face free trial expected to begin at the end of this year and our first in class <unk> technology is being assessed in the clinic to T X 200 with initial data from cohort one expected by the end of 2023.
Prathyusha Duraibabu: As the results of these changes were previously announced, 2023 Non-GAP
I'm very thankful to our leadership team and all my <unk> colleagues for their hardware can dedication to our mission.
Prathyusha Duraibabu: 23 The non-gap operating expense guidance range of $275 to $295 million is now obsolete. We expect our current estimate for 2023 to be in the range of $240 to $260 million. This range excludes certain non-cash charges, including estimated goodwill bite-down, 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 redouts from key programs will continue to drive decisions and investments in the coming months.
I'd like to close by expressing my hope and excitement for the future that lies ahead for <unk>.
So at this time, we'd like to open up for questions.
Operator, please open the line for questions.
Certainly as a reminder to ask a question. Please press star one one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one one again, please standby, while we compiled a Q and a roster and one moment fire first question.
And our first question will come from Ben Burnett Ave Stifle your line is open.
Alright. Thank you very much I had a question regarding the February program I was sorry, if you could provide more color on the potential phase three design being proposed to the F. T. A.
Prathyusha Duraibabu: In parallel, Sang was 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.
He says there is there any any expectation that that <unk> would be needed as a comparator and I guess, if so any thoughts as to whether or not a noninferiority study would suffice for for approval in the U S.
Alexander D. Macrae: Today you heard that Sangu is being responsible, responsive, and nimble in order to position itself for future success. There's a lot to look forward to.
<unk>. Thank you for your question I'm Gonna pass that went onto naturally.
Alexander D. Macrae: With hemophily A marching closer to a potential BLA submission, today we announced our wholly-owned neurology portfolio, centering around NAV-1.7, with an I&D 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 Fabri program advances towards a potential phase three trial expected to begin at the And our first in-class CART REG technology is being assessed in the clinic through TX 200, with initial data from cohort one expected by the end of 2023.
Hi, Thank you for the question we are preparing the interaction with the F. D. A right now we hope to have a meeting to stand there and we will come in on the face redesign and potentially agreement with C. F T. After the call.
Naturally for skating are going to that interaction some additional data from <unk> in the face went to trial that we are so it's it's simply just the time of collection of data absolutely.
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 I think the way the slides depicted as we understand it prion proteins I guess are continually supplying like material for the production of these larger misfolded aggregates.
Alexander D. Macrae: I am very thankful to our leadership team and all my thankful 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 Sanga. So at this time, we'd like to open up for a question. Operator, please open the line for questions. Certainly, 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. And one moment for our first question.
Is there anything known about whether aggregates will be cleared wants to pry on source turned off what what are you <unk>.
Jason can you help with that please yes. There is evidence that if the source of the of the prion protein aggregates. The the gene that prion gene is turned off that aggravates do diminish.
So so we believe that that this approach will have therapeutic potential and indeed that the data that we presented at.
Probably I'm 20 twenty-two showed great effects in in the preclinical mouse model. So we're very excited about this primer. Jason can you just summarize that data quickly about the difference in lifetime of my <unk> the dosing was given.
Operator: And our first question will come from Ben Burnett of Steeful.
Benjamin Jay Burnett: Your line is open.
Benjamin Jay Burnett: Hey, thank you very much. I had a question regarding the Fabray program.
Benjamin Jay Burnett: I was wondering if you could provide more color on the
Benjamin Jay Burnett: The potential phase three design being proposed to the FTA And is there any expectation that Fabra Zim would be?
Sure. So the the model that was used in that study is is considered a bold standard for understanding prion disease and we we took two approaches there one where the mice were inoculated with the prion protein, which <unk> initiated the disease and simultaneously.
Benjamin Jay Burnett: eat it as a comparator, and I guess if so, any thoughts as to whether or not a
Benjamin Jay Burnett: Not a non-inferiority study would suffice for approval in the U. Ben, thank you for your question. I'm going to pass that one on to Natalie.
Flea treated with the the zinc finger presser's, but we also took an approach where the the mice were inoculated and then the disease was allowed to start to develop and then a therapeutic application of the repressor was used and in both cases, our our <unk> our repressor.
Nathalie Dubois: Yeah, thank you for the question. We are preparing the interaction with the FDA.
Nathalie Dubois: Right now, we hope to have a meeting this summer, and we will comment on the phase three design and potential agreement with the FDA after the Natalie, what's gating, are going to that interaction?
Extended very significantly extended the lifespan of the mice and we compared this to data that has been published on Aso's and really impressive part of this was how much improved our our finger progressors warhead, extending the mice lifespans.
Nathalie Dubois: Some additional data from our tub dose in phase one to trial, but we are... So it's simply just the time of collection of data? Absolutely.
Benjamin Jay Burnett: Okay, that makes sense. I appreciate that. And maybe if I could also just ask a question, like a biology question on the prion disease program. I think the way the slides depicted is how we understand it,
Super interesting. Thank you.
Give me one moment for our next question.
Our next question will come from Greg Harrison a bank of America your lines open.
Benjamin Jay Burnett: As we understand it, prion proteins, I guess, are continually supplying 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? Jason, can you help with that, please?
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 Nah. If 1.7 is the target of focus.
How could you approach be differentiated from others like the small molecule blockers under development.
<unk>, Texas program.
Jason D. Fontenot: Yes, there is evidence that if the source of the prion protein aggregates, the gene, the prion gene, is turned off, aggregates do diminish. So we believe that this approach will have therapeutic potential. And indeed, the data that we presented at Pryon 2020 showed great effects in preclinical mouse models.
Greg. Thank you for the question and I'm Gonna pass on to Jason again to talk us through the science, but for those of US I've been an industry for any period of time, we've seen the number of companies I've tried to drunk on 1.7 and struggled with the fact that small molecules in <unk>.
Jason D. Fontenot: So we're very excited about this program. And Jason, can you just summarize that data quickly about the difference in the lifetime of mice and when the dosing was given? Sure.
Two bodies, the <unk> 1.7, and give clear benefit in pain.
Jason D. Fontenot: 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 prime 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 a therapeutic application of the repressors was used.
Interact with similar proteins, such as not 1.691, 0.8 and cause side effects. So Jason why why do we think our approach is so fundamentally different.
Yeah. So what's so exciting about that 1.7 is that there is very clear genetic data from from human populations that show that this this molecule is is a key regulator of pain sensation. So it has a very clear genetic.
Jason D. Fontenot: And in both cases, our repressors significantly extended the lifespan of the mice. And we compared this to data that has been published on ASOs, and really, the impressive part of this was how much better our zinc finger repressers were at extending the mice's lifespan. That's super interesting. Thank you. One moment for our next question.
It's genetically implicated in diseases, but as sandy pointed out the the problem with targeting Nab 1.7 has been that there. It's part of a family are very closely and simple structurally similar receptors and small molecule approaches in particular have been unable to to specifically target and at 1.7 without involving.
Operator: Our next question will come from Greg Harrison of Bank of America. Your line's open.
<unk> other receptors and this creates issues of of specificity. So what's unique about our zinc finger program is that we can design a an epigenetic repressor that very specifically targets Nab 1.7 without <unk>.
Gregory Allen Harrison: of America, your line's open. Hey, good morning. Thanks for taking our question. 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 your approach could be differentiated from others like the small molecule blockers under development, you know, like for a Texas program.
Without affecting the expression of any of the other closely related receptors and this allows us to do with small molecules are antibodies can do which is.
Gregory Allen Harrison: Greg, thank you for the question. And I'm going to pass it on to Jason again to talk us through the science. But for those of us that have been in the industry for any period of time, we've seen the number of companies I've tried to drug NAV-1.7 struggle with the fact that small molecules and antibodies that work on NAV-1.7 and give clear benefits in pain interact with similar proteins, such as NAV1.6 and NAP1.8, and cause side effects. So, Jason, why do we think our approach is so fundamentally different?
Only targeting at 1.7 and achieve this reduction in pain transmission without affecting the other the other the other processes that are regulated by the closely related receptors I wanted to just underline the ticket kind of simpler level.
The small molecules target the protein.
We do is we target the D N a and the D N a target for nothing 1.7 is completely different from all the other nuts and therefore, we do not have this problem of specificity because it should be any that we target note the protein.
Jason D. Fontenot: Yeah, so what's so exciting about NAV-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 link, genetically implicated in diseases. But, as Sandy pointed out, the problem with targeting NAV-1.7 has been that it's 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.
Does that help red.
Yeah, Yeah. That's that's super helpful. If I could think one morals.
I'm, just curious and and now that you're you're focusing you know <unk> under the one <unk> seven program and other earlier stage programs like Carty Reg what do you think partners to help fund development and just broader what's what's your strategy for fun in the pipeline.
And the more medium to longer time.
That's a very fair question Mark can you help with I'm sure Hi, Greg <unk>. Thanks for the question you know as <unk> as we've communicated before you know we're excited about our technology and when we get approached five you know potential partners that are interested in it.
Jason D. Fontenot: So what's unique about our Zingfinger 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 NAP 1.7 and achieve this reduction in pain transmission without affecting the other processes that are regulated by the closely related receptors. I want to just underline that and take it to a kind of simpler level. The small molecules target proteins.
We really ask yourself a couple of questions. One is you know can be kinda partners help us accelerate the program faster to patients by bringing resources expertise and capabilities.
And and if they do then that we take a serious look at that I mean, you know we've got a strong history over the last several years in terms of partnerships that have brought in about 850 million an upfront and you know we've seen a lot of progress as a result of those partnerships.
Alexander D. Macrae: 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, Brett? Yeah, that's super helpful. If I could sneak one more in, Just curious, now that you're focusing on the 1.7 program and other earlier stage programs like CARTREG, will you seek partners to help fund development and just be more broad? What's your strategy for funding the pipeline in the medium to launch? That's a very fair question, Mark. Can you help with that? Sure. Hi Greg.
Including Pfizer's advancements that I've <unk> commented on earlier, so we will look at that.
Great. Thanks for taking the question.
Can one moment for our next question.
Our next question will come from Gina Wang Barclays. Your line is open.
Thank you I also have one question.
At 1.7.
Awesome expressing ashley quite different tissue I'll spell that <unk> <unk> <unk>.
Yeah.
Other parts of the body so wonderful several questions.
What is it <unk> and <unk> and what is he on route of administration and how good.
Mark McClung: Thanks for the question. You know, as we've communicated before, we're excited about our technology. And when we get approached by, you know, potential partners that are interested in it, we really ask ourselves a couple of questions. One is, you know, can the partners help us accelerate the program faster to patients by bringing resources, expertise, and capabilities? And if they do, then we take a serious look at that. I mean, you know, we've got a strong history over the last several years in terms of partnerships that have brought in about 815 million up front.
Regarding a specific okay.
So there's there's three questions Gina <unk> <unk> route of administration wellness, a boat specificity, which I think we we have we partly addressed and the other one is at the longterm benefit to the patient.
So between Jason and Natalie can we addresses so Jason <unk> the specificity. Please and the route of administration sure. Thank you for the question Gina I think there are two important points about the specificity first the.
Mark McClung: And, you know, we've seen a lot of progress as a result of those partnerships, including Pfizer's, you know, advancements that I've commented on earlier. So we will look at that. Great. Thanks for taking the question. And one moment for our next question. Our next question will come from Gina Wang of Barclays. Your line is open.
<unk> this is where the power of our our zinc finger genomic engineering platform really comes comes to the to the front. We are able to design a zinc finger epigenetic repressor that are are are highly specific for Nab 1.7 and avoid for.
Huidong Wang: Thank you. I also have one question regarding NAF 1.7. I think it's also expressing quite different tissues as well, like pancreatic beta cells and olfactory sensory neurons.
Repression of any of the closely related receptors, but in addition to that.
N B a V 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 yet so by through the combination of both of those those mechanisms were able to achieve very selective ick.
Huidong Wang: There are a few other parts of the body. So, wondering, you know, several questions. One is, what is the advantage or disadvantage of long-term incubation? And what is your route of administration, and how good...
Huidong Wang: So there are three questions, Gina, that I heard. One is about the route of administration. One is about specificity, which I think we have partly addressed. And the other one is about long-term benefits to the patient. So Jason, do you want to talk about specificity, please, and the route of administration? Sure.
Expression in in the tissues that were 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 sort of the combination of our thing finger gene targeting caper.
Jason D. Fontenot: Thank you for the question, Gina. I think there are two important points about the specificities. First, um, this is where the power of our zinc finger genomic engineering platform really comes to the forefront. We are able to design zinc finger epigenetic repressors that are highly specific for NAB 1.7 and avoid repression of any of the closely related receptors.
Abilities, 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 through systemic administered.
<unk> sorry.
Excuse me entered legal administration.
<unk> yeah. So yeah, we we are targeting uhm.
Jason D. Fontenot: But in addition to that, in the AV vector that delivers this cargo, we can also use promoters that are specific to the cell type that we're interested in driving that repression. So through the combination of both of those mechanisms, we are able to achieve very selective expression in the tissues that we're 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 through the combination of our zinc finger gene targeting capabilities and our promoter engineering capability. In terms of delivery, or the dorsal root ganglion, we can achieve delivery through systemic administration. And so that is the approach that we are taking. Through systemic administration? Sorry, excuse me, intertical administration. Natalie, do you want to comment on that?
Population of <unk> <unk> <unk> <unk> see that I have chronic diseases. So we hope that the treatment will last for a long time, it's a one time single he called Valis injection.
The product and we we intend to do with Joseph condition trial that will allow us to uhm tie get the appropriate dose for reducing the pain in those patient and these visa patience. This this group that we're targeting as our first <unk>.
<unk> people with <unk>.
Intractable pain their lifestyle dominated and ruined by their intractable pain, we've had them come visit us at the company.
By doing it interesting <unk> by doing it with a promote to the specific in a visa is only going to appear in the in the around the dorsal root ganglion by zinc fingers it will only.
Nathalie Dubois: Yes, so, yeah, we are targeting a population of patients with 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, insosic bolus injection of the product.
Repress a single gene we get an enormous specificity benefit we we will show results. The S. G. C. T about animal experiments showed the benefit on pain, and we really feel that there's a root forward to your football is unimportant.
Alexander D. Macrae: And we, you know, intend to do a dose-escalation trial that will allow us to target the appropriate dose for reducing the pain in those patients. And these are patients, this group that we're targeting as our first population or people with intractable pain. Their lives are dominated and ruined by their intractable pain. We've had them come visit us with the company. By doing it intricately, by doing it with a promoter that's specific, an AV that is only going to appear in the, around the dorsal root ganglia, and by zinc fingers, it will only repress a single gene.
Significant medical unmet need.
And importantly.
Importantly, I think it may add that reducing pain by any <unk> seven it's not known to be associated with any neurological side effects and other sensory modality not expect it to be affected.
A specific time getting yeah.
Uhm Yeah. My question also like a long time, <unk> and it could be <unk>.
So we will do this do you know you you know as well and you know how seriously we take patient benefit in patient safety and so we will start at at at the appropriate deal was agreed with the agency and gradually increase it but I I <unk>.
Alexander D. Macrae: We get an enormous specificity benefit. We will show results at ASGC of 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. And importantly, I think I may add that reducing pain by inhibiting NAB1.7 is not known to be associated with any neurological side effects, and other sensory modality is not expected to be affected. So, very specific targeting. So yeah, my question also, like a long-term inhibition, you know, what could be a disadvantage there?
Let's see importantly enough <unk> <unk> seriously impacted these patients are by their pain. So for them. This is an enormous advantage and we've consulted with them we've had them come in to companies and they they see this as a really promising <unk>.
Future medicine.
Okay.
One moment for our next question.
Your next question will come from <unk> Mare Ray Croft, if geoffrey's the line is open.
Alexander D. Macrae: So we will do this, you know as well, and you know how seriously we take patient benefit and patient safety. And so we will start it at the appropriate dose agreed with the agency and gradually increase it. But I cannot say 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 method. One moment for our next question. Our next question will come from Maury Raycroft of Jeffries. The line is open.
Hi, Good morning, Thanks for taking my questions, maybe it's follow up to Gina as question. You you mentioned in the south specific promoter in interest equal delivery can you talk more about capsid desert gating factor for program advancement.
Yes.
You would like to clarify that for the previously partner Biogenic Novartis programs. One of the reasons why those are paused for now is primarily because of a V delivery limitations and will you use a novel Sangamo capsid for Nab, 1.7, and prion or conventional caps and like.
Like a V nine because you need lifestyle blood brain barrier penetration and distribution for those targets.
Maurice Thomas Raycroft: Hi, good morning. Thanks for taking my questions. Maybe as a follow-up to Gina'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 partnered by Agenna Novartis programs, one of the reasons why those are paused for now is primarily because of AAB delivery limitations. And will you use a novel Cangamo Capsid for NAV 1.7 and Preon or a conventional capsid, like A, because you need less blood-brain barrier penetration and distribution for those
Good morning Mare. Thank you for the questions. So, we're not revealing which capsize, we're using for which diseases at this time.
But we we believe that we have a solution for each of the ones that were advancing.
<unk> talking about the <unk> programs for example, Alzheimers the the challenge for that is ensuring that we have widespread bringing coverage, particularly for the regents are most impacted by Alzheimer's.
Maurice Thomas Raycroft: Good morning, Maury. Thank you for the question. So we're not revealing which capsids we're using for which diseases at this time, but we believe that we have a solution for each of the ones that we have advanced. 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. And so we've paused that program.
An intravenous manner, we believe and and so we <unk> program. It is upon significantly over the three years has been with with <unk>.
We are making great strides with our caps at evolution, we are watching with interest other people's caps that evolution change and when when there is progress and I truly believe that will be progressing of blood brain barrier crossing caps it.
Jason D. Fontenot: It has advanced significantly over the three years it's been with biogen. We are making great strides with our capsid evolution. We are watching with interest other people's capsid evolution changes. And when there is progress, and I truly believe there will be progress in a blood-brain barrier crossing capsid in the near future, those assets suddenly become very attractive for us or for other people.
In the suit in future do as asset suddenly become very attractive for us or for other people.
Got it that's helpful. Thanks for taking my questions.
Thank you Maureen.
Next question.
And our next question will come from your <unk> Tzu of Wells Fargo. Your line is open.
[noise] hi, thanks for taking our questions on the NAV 1.7.
Jason D. Fontenot: Got it, that's helpful. Thanks for taking my question. One moment. Thank you, Maureen. Far next.
Program, just wondering uhm what percentage of suppression of expression are you driving for and expecting to have benefits and.
Operator: for our next question. And our next question will come from Yanan Zoo of Wells Fargo. Your line is open.
Yanan Zhu: Hi, thanks for taking our questions. On the NAV-7 program, I just wondered what percentage of suppression of expression are you driving for and expecting to have benefit? And also, are there advantages for using a transcription repressor approach as opposed to a straight knockout approach since you have both technologies?
And also is there are there advantages for using.
Transcription repressor approach as opposed to straightened.
Straightened out <unk> approach since you have those technologies.
Thanks.
Yanan Zhu: Jason, this sounds like a technical question for you. Yeah, thank you for the question. So, maybe I'll start with the second question.
Yes in the sense like a technical question for Ya.
Yeah. Thank you for the question.
So maybe.
Maybe I'll start with the second question. We we are really excited about our our epigenetic repression platform and we believe that it's really optimal for this particular approach for a few reasons one because we were <unk>, we were able to deregulate the jeans.
Jason D. Fontenot: 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 are able to regulate genes without the introduction of double-stranded breaks or any type of mutation, and we're able to do that very specifically and very potent. 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.
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 per cent close to quantitative repression of the target gene using this approach and we <unk> we <unk>.
Believe it will be stable for <unk> for for longterm. So we're very excited about the approach and believe it's superior, especially in the CNS, where silva non dividing than using been using nucleases for instance, or or any kind of approach that modifies the DNA permanently.
Jason D. Fontenot: So we're very excited about the approach and believe it's superior, especially in the CNS, where cells are non-dividing, than using nucleases, for instance, or any kind of approach that modifies the DNA permanently. However, regarding how much repression is needed, I think there's two things to be considered there. There's the per cell repression and the coverage, the number of cells that are being repressed. What's really great about our platform is that, on a per cell basis, we can design repressors that repress gene expression to the amount that we think is needed to achieve the biological and therapeutic effect.
Regarding how much repression is needed I think there's two there's two things to be considered there. There's the personnel repression and the coverage the number of cells that are being repressed, what's what's really great about our platform is that on the personnel basis, we can design work presser's that.
Request gene expression to the amount that we think is needed to achieve the biological and therapeutic effect and so we've identified were presser's that are very potent at the single cell basis, and then threw dosing in animal models, we will explore what level of repression.
Jason D. Fontenot: And so we've identified repressors that are very potent at the single cell level. 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, you know, what range of doses we want to explore before taking that into patients.
Cross multiple cell types is necessary to achieve the appropriate therapeutic production in pain and that will be that will be done by by dosing in in preclinical models to understand you know what what range of doses, we want to explore and then we'll take that into patients.
Yanan Zhu: Got it, thank you. And maybe also a question, maybe two quick questions, one on
Got it. Thank you and maybe also question maybe two quick questions on the February see these program.
Yanan Zhu: Faber disease program, could you comment on whether those patients who were off ERT remain off?
Could you comment on whether those patients who were off E. R T.
Yanan Zhu: off at this moment.
Yanan Zhu: Or should we have to wait until the next data update to hear about that? Natalie, can you update that? Yeah, so far.
Remains all everything off at this moment.
Should should we do we have to wait until the next data update to to hear about that thanks.
Nathalie Dubois: Yeah, so far, all the patients that have been withdrawn from ERT are still on ERT.
Lastly, can you update that yeah. So far all the patient that has been withdrawn from the I T I still Oh C I T.
Nathalie Dubois: Very helpful. And lastly, for the TX 200 program, Um, will you move to a higher dose sometime this year? It sounds like I think the first cohort designed to have three patients, and it sounds like you have all three. So could you talk about potential decisions for those exclamations there? Yeah, yeah, that's a question. Bettina, can you help us with us?
Very helpful and lastly for the T X 200 program.
Uhm.
<unk>.
<unk> will you move to a higher dose sometime this year is because sounds like I think the first cohort Ah designed is designed to have three patients and it sounds like you had those those are three so could you talk about potential decisions for.
Those escalation there.
And.
Yeah, Yeah that that's the question. Thanks.
Bettina can you help with them yes.
Bettina M. Cockroft: Yes, and thank you for the question. We're extremely happy.
Yes, absolutely and thank you for that question. So we're extremely I'm happy to have concluded enrollment and dosing in cohort one for T. X 200, we plan to have a safety monitoring committee meeting.
Bettina M. Cockroft: to have concluded enrollment and dosing in cohort 1 for TX 200. We plan to have a safety monitoring committee meeting.
Bettina M. Cockroft: 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.
I'm coming up very shortly in May so that we can then move onto the next cohort and we already have patience lined up.
And we're excited by this we have also recently engaged with regulatory agencies in Europe , who are mm mm representing the countries, where we're conducting the trial that have agreed to and optimize design of a dose escalation protocol.
Bettina M. Cockroft: with regulatory agencies in Europe who are representing the countries where
Bettina M. Cockroft: Presenting the 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 those escalation. And then we'll plan to share initial data from cohort one by the end of this year.
Call in so this means we we hope to accelerate those escalation and then wrote plan to share initial data from cohort one by the end of this year.
Bettina M. Cockroft: Got it. Thanks for all the updates. One moment for our next question.
Got it thanks for the update.
And one moment for our next question.
Operator: Our next question will come from Luca Izzy of RBC. Your line is open.
Our next question will come from Luca <unk> of RBC. Your line is open.
Luca Issi: Oh, excellent. Thanks for taking our questions. This is Lisa Onfaluka.
Oh excellent thanks for taking our questions. This is lisa onto Luka.
Luca Issi: Maybe just one here first on the restructuring efforts 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?
Maybe just one here first on the restructuring assets.
Today, just wondering what other initiatives are being explored to either preserve capital R. A fun and have you thought about potentially monetizing the royal tasting first in this area.
Luca Issi: Thank you for the question. The restructuring was a very important part of our
Thank you for the <unk>. The question the restructuring was a very important part of her announcement today <unk> can you comment on this.
Alexander D. Macrae: 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, you know, ways of running Sangamo as a leaner-focused organization.
Yeah, Yeah, Sandy said today's restructuring with a difficult decision, but it was on the line with so I could take priority is the outline on the call and will continue to assist you know basis N running sang in Melissa email focused organization.
Prathyusha Duraibabu: 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.
As far as seven evaluating the different flavors uhm for extending our cash runway at the clinical company were actively pursuing different opportunities for financing and we we will look at them.
Prathyusha Duraibabu: different avenues, including royalty monetization. I think that's helpful. Go ahead, Sandy.
Different avenues, including the royalty my technician.
Alright <unk> <unk>.
Alexander D. Macrae: It's a significant return or rep for you for San Camo 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 mention, the more valuable it is. And so that's the balance that Prathusha is constantly looking at about near-term cash versus long-term value, all of which will lead to returns for our shareholders. That's right. That's helpful; thanks.
Go ahead Sandy it's.
It's a significant.
Return or <unk> in the future.
And we need simply to be thoughtful about when we access that <unk> the closer it gets too.
Uhm submission and hopefully marketing of unimportant medicine, the more valuable it is and so that's the balance that <unk> constantly looking at <unk> near term cash versus longterm <unk>, all of which will lead to return for shareholders. That's right.
Luca Issi: And maybe just one on the T-Regs, more of a big picture question. You know, you're going to get some data maybe later by year end. Just thinking, you know, what are the next steps for T-Rigs?
That's helpful. Thanks, and maybe just one.
<unk> alright, let them catch that question.
<unk> <unk> can I get some good data Navy later, a year and and just just thinking you know what I'm gonna be the next step spiky red send the data be positive well this accelerate you're thinking I'm living at towards an auto any medication.
Luca Issi: Should the data be positive, will this accelerate your thinking on moving towards an autoimmune indication?
Mark McClung: Mark, can you help us think about the T-Rex? So, excuse me. Thanks, Lisa.
Mark can you help us think about the T. Rex please.
Mark McClung: Yeah, I mean, as we've talked about, TX200 is a perfect biological model to assess the performance of T-Regs. 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 pre-clinical programs, and they're continuing to progress. MOG for multiple sclerosis and IL-23 for inflammatory bowel disease. Both of those programs, as we've talked about, are where we're focusing.
<unk> excuse me, thanks, <unk>, Yeah, I mean cause.
Cause we talked about checks 200, we think is a perfect biologic model to assess the performance of T. Rex and so we're really excited about that it will be looking forward to providing an update as we mentioned towards the end of the year. We do have our preclinical programs are continuing to progress maag for multiple sclerosis.
Process and I'll twenty-three for inflammatory bowel disease, both of those programs as we've talked about we're focusing primarily on the autologous to to ensure we can move them forward towards I N D. S and so we're very committed to that and excited to to continue. This we've got a lot of you know a lot of focus to X.
Mark McClung: primarily on the autologous to ensure we can move them forward towards I&D. And so we're very committed to that and excited to continue this. We've got a lot of, you know, a lot of focus to execute against the preclinical work on both of those assets as we continue to execute on the TX 200 trial.
<unk> against the the preclinical work on both of those assets as we continue to execute on the T X 200 trial.
Operator: Thanks, thanks for taking our question. One moment for our next question.
Alright, thanks, Thanks for taking my question.
And one moment for next question.
Patrick Ralph Trucchio: And our last question comes from Patrick Trucio of H.D. Waring. Right, your line's open.
And our last question comes from Patrick Juicy out of HD Wainwright Your line Sir.
Patrick Ralph Trucchio: Thanks, good morning. I just have a few follow-up questions on some that were asked earlier. The first was just, I was wondering if you could just talk a little bit more about the Sifter platform and how it enables selection of CNS-tropic AAV capsids. And in particular, you know, with regard to these neuro programs, what are you actually looking for in the identification and selection of engineered AAV capsids for enhanced CNS delivery?
Thanks, Good morning, I I just have a few follow up questions from some a few that had been asked earlier I. The first was just I was wondering if you can just talk a little bit more about the sensor platform and how it enables selection of CNS traffic <unk> than in particular, you know with regard to these Nero program.
What what are you actually looking for any identification selection of the engineered Avi caps ads for enhanced C. N S delivery and then just just separately just with a hearty Reg I'm. Just wondering you know with the intention to prioritize the near term autologous portfolio can you. Please provide some additional uhm details or around this.
Patrick Ralph Trucchio: And then just separately, just with the CART reg. I'm just wondering, you know, with the intention to prioritize the near-term autologous portfolio, can you provide some additional details around this decision, how it will perhaps accelerate the I&Ds for the broader indications like MS and IDD?
Decision, how it <unk>, perhaps you know accelerate the I N D. S for the broader indications like M. S N I D D.
Jason D. Fontenot: So let's answer, Patrick, thank you for your question. Let's try and answer this in two ways. Jason, can you take the capsids, please, and Mark, can you talk about T-Rex, please? 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.
So let's answer Patrick. Thank you for your question, let's try not to listen to waste Jason can you take caps its police and Mark can you talk about T. Rex Please [noise].
Sure. Thanks for the question Patrick So we're we're really excited about the work in our capsid evolution group and I guess I guess I can take the question and in two different ways. There's the actual technology that we're <unk>, we're using to to develop and evaluate capsid, but there's also the approach that were.
Jason D. Fontenot: 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 group, the 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.
Jason D. Fontenot: 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 the treatment needs to be targeted. And so for different diseases, those are different areas of the brain. Sometimes there are areas in the peripheral nervous system.
The brain or and then in the nervous system needs to be targeted and so for different diseases that those are different different areas of the brain. Sometimes there are areas of the peripheral nervous system and so once we identify where we want to target than we think okay. What is the best caps it to do that and we have a team that is <unk>.
Jason D. Fontenot: 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. And we evaluate specific pathways that are known to facilitate transport across the blood brain barrier.
<unk> capsid libraries that are both targeted so we we evaluate specific pathways that are known to facilitate transport over the blood brain barrier and we have we have captured libraries that are more random.
Jason D. Fontenot: 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 specific indications.
Jason D. Fontenot: And so that's the approach that we use to look for novel capsids. So we have an idea of a whole set of indications and areas of the nervous system that we're interested in targeting. And we're using these libraries that can be done.
Jason D. Fontenot: 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, then we're obviously excited to move forward. So Patrick, on the Tregs, I mean, I want to frame this in a couple of ways.
Designed to be delivered by direct injection and we use both of those approaches to look for <unk> that we think can get us to to the a therapeutic effect that we need and once we have one of those in hand, and we're obviously excited to move forward.
So Patrick on the on the <unk> I mean, I I I bought a frame. This in a couple of ways. One as we all know access to capital. These days is a challenge.
Mark McClung: 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 TREGs, we had to make a choice to really focus on TX200 and the execution of that trial to prove the concept, while keeping the Mog and IL23 preclinical auto programs, which are a little more advanced moving forward.
And as a result of that and you know with the 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 in in the case of the T. Rex we had to make a choice to really focus on T X 200, and the execution of that trial to the proof of concept and keeping them organ I'll twenty-three preclinical auto programs, which are a little more.
Fast moving forward. So we've had to make a difficult choice two deprioritized the aloe at work until the future, but you know I I wanted to say that our investors also say to us that they are very interested in the T regs and they would love to invest in the T. Rex and so you know we're <unk>.
Mark McClung: So we've had to make a difficult choice to deprioritize the Allo work for the future. But, you know, I want to say that our investors also tell us that they're very interested in the T-Rags and they would love to invest in the T-RGs. And so, you know, we're assessing how best we can set ourselves up to do that. But in the meantime, we're also looking into and having conversations with interested parties around partnerships.
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 added ended up having a partnership come in one of the thing we'd want them to do is bring enough you know money and expertise in that we can restart those programs and accelerate them again, but it's purely a.
Mark McClung: If we ended up having a partnership come in, one of the things we'd want them to do is bring enough, you know, money and expertise so that we can restart those programs and accelerate them again. But it's purely a choice that we've, you know, that we've had to make, unfortunately.
Choice that <unk>, you know that we've had to make unfortunately.
Mark McClung: That's helpful. Thank you very much, and I'm showing no further questions. I would now like to attend the call.
That's helpful. Thank you very much.
And I'm showing no further questions I would now like to turn the call back over to Luis Loki for closing remarks.
Louise Wilkie: I would now like to call back over to Louise Wilkie for closing remarks.
Louise Wilkie: Thank you once again for joining us today and for all your questions. As a reminder, you can access the earnings release and presentation in the Investor Relations section of the Sangoma website. We look forward to keeping you updated on our future developments.
Thank you once again for joining us today and for your questions. As a reminder, you can access the earnings release and presentation on Investor Relations section of the sign up on our website, we look forward to keeping up base. It on a feature developments. Thank you.
Operator: This concludes today's conference call. Thank you for participating. You may now disconnect.
This concludes today's conference call. Thank you for participating you may now disconnect.