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Taysha Gene Therapies, Inc. (TSHA) Q4 2021 Earnings Call Transcript

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Taysha Gene Therapies, Inc. ( TSHA -2.76% )
Q4 2021 Earnings Call
Mar 31, 2022, 8:00 a.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Welcome to the Taysha Gene Therapies fourth quarter and full year 2021 financial results and corporate update. [Operator instructions] As a reminder, this call is being recorded today, March 31, 2022. I will now turn the call over to Dr. Kimberly Lee, chief corporate affairs officer.

Please go ahead.

Kimberly LeeChief Corporates Affair Officer

Good morning, and welcome to Taysha’s fourth quarter and full year 2021 financial results and update conference call. Joining me on today’s call are R.A. Session II, Taysha’s president, founder, and CEO; Dr. Suyash Prasad, chief medical officer and head of R&D and Kamran Alam, chief financial officer.

After our formal remarks, we will conduct a question-and-answer session, and instructions will follow at that time. Earlier today, Taysha issued a press release announcing financial results for the fourth quarter and full year ended December 31, 2021. A copy of this press release is available on the company’s website and through our SEC filings. Please note that on today’s call, we will be making forward-looking statements, including statements relating to the safety and efficacy and the therapeutic and commercial potential of our investigational product candidates.

These statements may include the effect, the timing, and results of clinical trials for our product candidates; our expectations regarding the data necessary to support regulatory approval of TSHA-120; the regulatory status and market opportunity for our clinical programs; as well as Taysha’s manufacturing plans. This call may also contain forward-looking statements relating to Taysha’s growth and future operating results, discovery and development of product candidates, strategic alliances, intellectual property, cash runway, and implementation and potential impacts of our strategic pipeline prioritization initiatives, as well as matters that are not of historical facts or information. Various risks may cause Taysha’s actual results to differ materially from those stated or implied in such forward-looking statements. These risks include uncertainties related to the timing and results of clinical trials and preclinical studies of our product candidates, our dependence upon strategic alliances and other third-party relationships, our ability to obtain patent protection for our discoveries, limitations imposed by patents owned or controlled by third parties and the requirement of substantial funding to conduct our research and development activities.

For a list and a description of the risks and uncertainties that we face, please see the reports we have filed with the Securities and Exchange Commission. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, March 31, 2022. Taysha undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call, except as may be required by applicable securities law. With that, I’d now like to turn the call over to our president, founder, and CEO, R.A.

Session II. R.A.? 

R. A. SessionPresident, Founder, and Chief Executive Officer

Thank you, Kim. Good morning and welcome, everyone, to our call. 2021 was a year of accomplishments that included positive data from three clinical programs, including GAN, GM2 gangliosidosis, and CLN7 disease. We are sharpening our strategic focus to prioritize key value-driving, registration-directed programs in GAN, which has an estimated addressable patient population of 5,000 worldwide; and Rett syndrome, which affects over 350,000 patients worldwide.

To increase operational efficiency, activities for other ongoing clinical programs will be minimized and all other research and development will be paused. As a result, we have reduced our workforce by approximately 35%. Our strategic pipeline prioritization, along with existing cash and financing under our current debt facility, is expected to extend cash runway into the fourth quarter of 2023. We look forward to our continued execution across our clinical and regulatory strategy, and we’ll update you on progress throughout the remainder of the year.

I will now turn the call over to Suyash to provide a more detailed update on our clinical program. Suyash, please go ahead. 

Suyash PrasadChief Medical Officer and Head of R&D

Thanks, R.A. Recently, we reported positive initial clinical data for GAN, GM2 gangliosidosis, and CLN7 disease, further validating the therapeutic potential of our platform in multiple diseases of the central nervous system. Let’s begin with TSHA-120 for the treatment of GAN. TSHA-120 is the first gene therapy to be intrathecally dosed and is currently being evaluated as part of a groundbreaking, historic dose-escalation clinical trial at the NIH under the leadership of the principal investigator, Carsten Bonnemann.

We recently reported positive clinical efficacy and safety data for the high-dose cohort of 3.5E14 total vg, as well as long-term safety and durability data across all therapeutic doses. Treatment with TSHA-120 achieved a clinically meaningful and statistically significant slowing or halting of disease progression seen in the highest-dose cohort of 3.5E14 total vg and across all therapeutic dose cohorts. At the highest dose, TSHA-120 demonstrated clinically meaningful and statistically significant improvements in the MFM32 score by year one compared to natural history. Additionally, long-term durability data across all therapeutic doses demonstrated a 10-point improvement in the mean change from baseline in MFM32 score by year three compared to the estimated natural history decline of 24 points.

These long-term data confirm the disease-modifying effect and sustained durability of TSHA-120. Notably, nerve biopsy data pre and post treatment with TSHA-120 provided evidence of active regeneration of nerve fibers, thereby demonstrating pathological improvement to complement the clinical benefits seen. In addition, preservation of visual acuity, as measured by the LogMAR scale was observed. And this was in conjunction with improvements in retinal nerve fiber layer thickness as assessed by optical coherence tomography.

There were no significant safety issues and no increase in adverse events at high doses. All adverse events related to immunosuppression or study procedures were comparable to other gene therapies and transient in nature. There were no dose-limiting toxicities reported following treatment with TSHA-120, no evidence of dorsal root ganglion inflammation, and no evidence of thrombocytopenia. Overall, this dataset is the most comprehensive gene therapy dataset in GAN, offering TSHA-120 a potentially derisked regulatory path.

We believe this program currently meets most registration requirements based on FDA and EMA’s guidance for gene therapy for neurodegenerative diseases. We look forward to our continued discussions with major regulatory agencies on potential registration pathways for TSHA-120 and anticipate a regulatory update by mid-2022. As a reminder, TSHA-120 has already received orphan drug and rare pediatric disease designations from the FDA. We also have partnerships in place to help raise awareness and facilitate early diagnosis of GAN.

This includes a partnership with GeneDx, the global leader in genetic testing, to include a genetic marker to test for GAN and the GeneDx routine hereditary neuropathy screening panel, which is free of charge to individuals at risk of or suspected of having GAN. It also includes collaborations with Hereditary Neuropathy Foundation and the Charcot-Marie-Tooth Association Centers of Excellence, as well as healthcare professionals and patient advocacy groups, to increase access to genetic testing. Turning to Rett syndrome. TSHA-120 is the first and only gene therapy in clinical development for Rett syndrome and is designed to deliver a MECP2 transgene using our novel miRARE platform or a microRNA-Responsive Auto-Regulatory Element platform.

The technology is exclusively licensed to Taysha and developed by Drs. Sarah Sinnett and Stephen Gray of UT Southwestern Medical Center. miRARE is designed to provide sophisticated regulation of transgene expression genotypically on a cell-by-cell basis, delivering controlled expression that prevents toxicity associated with excessive levels of MECP2. We were very pleased to announce earlier this week initiation of clinical development for TSHA-102 with the acceptance of our CTA by Health Canada in March.

Sainte-Justine Mother and Child University Hospital Center in Montreal, Québec, Canada has been selected as the initial clinical site under the direction of Dr. Elsa Rossignol, principal investigator. We also announced positive preclinical data that supported the CTA acceptance, including the pharmacology study in Rett knockout mice assessing the efficacy of TSHA-102 and the six-month GLP toxicology study in nonhuman primates exploring the biodistribution and mechanism of action of TSHA-102. TSHA-102 has a robust preclinical data package that supports and validates the ability of miRARE to safely regulate transgene expression.

Data from the IND/CTA-enabling pharmacology study in mouse models of Rett syndrome demonstrated that miRARE-regulated transgene expression improved survival, respiratory function, and motor function assessments across multiple dose levels. A one-time intrathecal injection of TSHA-102 significantly increased survival at all dose levels, with the mid to high doses improving survival across all age groups compared to vehicle-treated controls. Treatment with TSHA-102 significantly improved body weight, motor function, and respiratory assessments in MECP2 knockout mice. An additional study in neonatal mice is currently ongoing with preliminary data suggesting normalization of survival.

Positive IND/CTA-enabling six-month GLP toxicology data in NHPs reinforced TSHA-102’s favorable safety profile across all dose levels tested, including doses up to fourfold above the presumed clinical starting dose, these data supported by distribution, as reflected by DNA copy number in multiple areas of the brain and sections of spinal cord. Perhaps most importantly, we observed correspondingly low levels of mRNA across multiple tissues. This indicate that the miRARE downregulation is appropriately minimizing transgene expression from the construct in the presence of endogenous MECP2 in these wild-type NHPs, as expected. Let me repeat that.

High levels of DNA in target tissues, meaning that there’s good distribution of drug from an intrathecal injection, but low levels of mRNA, meaning that the downregulation by the miRARE platform is working well to minimize any toxicity. Indeed, no toxicity from transgene expression was observed, which was confirmed by functional evaluations demonstrating no detrimental change in neurobehavioral assessments and histopathologic evaluations demonstrating no adverse tissue findings or necropsy. Collectively, these data further support the therapeutic potential, safety, and tolerability of TSHA-102 to treat Rett syndrome across a broad dose range. These preclinical safety and efficacy data will be presented at the International Rett Syndrome Foundation Rett Syndrome Scientific Meeting taking place April 26 to 27, 2022 in Nashville, Tennessee.

Currently, there are no disease-modifying therapies to treat over 350,000 patients estimated to suffer from Rett syndrome worldwide. We’re excited to advance TSHA-102 as the first gene therapy in clinical development for the treatment of this devastating neurodevelopmental disorder and look forward to reporting preliminary Phase 1/2 clinical data by the end of 2022. As a reminder, TSHA-102 has been granted rare pediatric disease designation and orphan drug designation from the FDA and, more recently, orphan drug designation from the European Commission. For GM2 gangliosidosis, TSHA-101 is the first and only bicistronic vector in clinical development, representing an important first for the field of gene therapy.

Driven by the same promoter, TSHA-101 expresses both the Hex A gene, coding for the alpha subunit, and the Hex B gene, coding for the beta subunit, in a 1:1 ratio, enabling the production of functional heterodimeric beta-hexosaminidase A and providing the ability to restore and normalize enzyme activity in GM2 gangliosidosis using one vector. We reported initial positive biomarker data in January for TSHA-101, demonstrating normalization of beta-hexosaminidase A, or Hex A, enzyme activity in patients with multiple forms of GM2 gangliosidosis. We shared data for two patients, including month-one and month-three analyses for a patient with Sandhoff disease and month-one analysis for a patient with Tay-Sachs disease. Following one intrathecal administration, TSHA-101 achieved Hex A enzyme activity of 190% of normal at month one and 288% of normal at month three in patient one with Sandhoff disease, representing 38-fold and 58-fold above the presumed asymptomatic level of 5% of normal identified by natural history at month one and month three, respectively.

Patient two with Tay-Sachs disease achieved Hex A enzyme activity of 25% of normal at month one, which represented fivefold above the presumed asymptomatic level of 5% of normal identified by natural history. Preliminary data suggested that TSHA-101 was well tolerated with no significant drug-related events in both patients. The unfortunate death of patient one was attributed to pneumonia and pleural effusion with a concomitant hospital-acquired MRSA infection. The independent data safety monitoring board agreed with the initial assessment from the principal investigator and confirmed that the patient’s death was unrelated to study drug.

Patient two continues to progress well. And we are continuing to monitor patients two and three. We do not intend to pursue further enrollment in the Phase 1/2 trial at this time due to prioritization of programs to increase operational efficiency. But we will continue to follow the patients who were previously dosed.

For CLN7, we reported positive preliminary clinical safety data for the first-generation construct in CLN7 Batten disease from the ongoing clinical trial in collaboration with UT Southwestern and Children’s Health and Children’s Medical Center Foundation. We recently dosed the fourth patient at 1E15 total vg, bringing the total to three out of the four patients dosed at 1E15 total vg, which is the highest dose ever safely administered intrathecally in humans for gene therapy. Dose escalation from 5E14 to 1E15 total vg was supported by the data safety monitoring board. Initial data from three patients supported a favorable tolerability and safety profile with no major adverse events across doses.

Further development of the CLN7 program will focus solely on the first-generation construct in collaboration with our existing partners. In 2022, we expect several potential value-creating catalysts, including regulatory feedback for TSHA-120 in GAN by mid-2022 and preliminary Phase 1/2 data for TSHA-102 in Rett syndrome by year end. Clinical development of the first-generation construct for CLN7 remains ongoing with our existing partners. We will continue clinical development of TSHA-118 in CLN1 disease and expect to initiate clinical development of TSHA-105 in SLC13A5 deficiency this year.

With that, I’ll turn the call over to Kamran to review our financial results. Kamran? 

Kamran AlamChief Financial Officer

Thank you, Suyash. This morning, I will discuss key aspects of our first quarter and full year ended December 31, 2021, financial results. More details can be found in our Form 10-K, which will be filed with the SEC shortly. As indicated in our press release today, research and development expenses were $37.9 million for the three months ended December 31, 2021, compared to $12.3 million for the same period in 2020.

Research and development expenses were $131.9 million for the full year ended December 31, 2021, compared to $31.9 million for the full year ended December 31, 2020. The $100 million increase was primarily attributable to an increase of $38.3 million of expenses incurred in research and development, manufacturing, and other raw material purchases, which included cGMP batches produced by Catalent and UT Southwestern. We also incurred an increase in employee compensation expenses of $32.7 million, which includes $7.1 million of noncash stock-based compensation due to an increase in the employee headcount in the research and development function. We also incurred an increase of $29 million of third-party research and development consulting fees primarily related to GLP toxicology studies, clinical study CRO activities, and consulting for regulatory and clinical studies.

General and administrative expenses were $11.8 million for the three months ended December 31, 2021, compared to $6.1 million for the three months ended December 31, 2020. General and administrative expenses were $41.3 million for the full year ended December 31, 2021, compared to $11.1 million for the full year ended December 31, 2020. The full year increase of approximately $30.2 million was primarily attributable to $16.3 million of incremental compensation expense, which included $7.7 million of noncash stock-based compensation due to increases in employee headcount. We also incurred an increase of $13.9 million in professional fees related to legal, insurance, investor relations, communications, accounting, personnel recruiting, market research, and patient advocacy activities.

Net loss for the three months ended December 31, 2021, was $50.4 million or $1.32 per share as compared to a net loss of $18.3 million or $0.50 per share for the three months ended December 31, 2020. Net loss for the full year ended December 31, 2021, was $174.5 million or $4.64 per share, compared to a net loss of $60 million or $3.40 per share for the full year ended December 31, 2020. As of December 31, 2021, Taysha had $149.1 million in cash and cash equivalents. Our strategic pipeline prioritization initiatives, along with existing cash and financing under the current debt facility, is expected to extend cash runway into the fourth quarter of 2023.

And with that, I will hand the call back to R.A. 

R. A. SessionPresident, Founder, and Chief Executive Officer

Thanks, Kamran. This year, we are focused on strategic pipeline prioritization initiatives for GAN and Rett syndrome and our plans to conduct small proof-of-concept studies in CLN1 disease and SLC13A5 deficiency. We anticipate several potentially value-creating catalysts this year, including a regulatory update for TSHA-120 in GAN by midyear and preliminary clinical data for TSHA-102 in Rett syndrome. I would like to give special thanks to the continued support and dedication of our Taysha employees, board of directors, scientific advisory board, collaborators, and the patients and advocates who remain our motivation every day to continue our mission to develop curative gene therapies to eradicate devastating monogenic CNS disease.

I will now ask the operator to begin our Q&A session. Operator? 

Questions & Answers:

Operator

Thank you. [Operator instructions] And our first question comes from the line of Salveen Richter with Goldman Sachs. Please proceed with your question. 

Elizabeth WebsterGoldman Sachs — Analyst

Hey, good morning. This is Elizabeth on for Salveen. Just given the strong data that you had for GM2 this year, I guess why choose to deprioritize that program?

R. A. SessionPresident, Founder, and Chief Executive Officer

Hi, Elizabeth. Good morning. Hopefully, you can hear me OK. I think it really boils down to really focusing on a couple of key value drivers this year.

Just with the uncertainty in the capital markets from a fundraising perspective, I think it was really imperative to put the company in the best possible position for when Rett data would be available as that’s a pretty large opportunity. We’re talking about 350,000 patients worldwide and really the significant unmet medical need there. What I would say is I think there’s always the opportunity to take a different — another look at prioritization once we see external factors stabilize somewhat. But I think this is really — this was extremely important to make sure that the company itself was put in the best possible position to preserve cash runway but also value creation.

Obviously, the focus on GAN is pretty evident because we’re going to be embarking on regulatory pathway discussions. And then Rett is just such a large opportunity and one that we’re going to be the first and only gene therapy in development where a lot of other companies haven’t made it that far we thought it was just prudent for us to focus there. So hopefully, that answers your question.

Operator

Thank you. Our next question is from the line of Joon Lee with Truist Securities.

Joon LeeTruist Securities — Analyst

Hi. Thanks for taking our questions. In addition to restructuring, would you also consider monetization of some of the noncore programs via out-licensing or partnering? And then also, our understanding is that the term loan from SVB Leerink — SVB is contingent upon you having three active programs. So in addition to GAN or Rett, do you plan to have a third program still active? Thank you. 

R. A. SessionPresident, Founder, and Chief Executive Officer

Hey, Joon. Good morning. Thanks for the questions. I’ll take the last question first.

So I think as we stated, there’ll be a key focus on GAN and Rett syndrome, but we’re also going to be continuing development on CLN1, CLN7, and SLC13A5. So in total, there’s five active programs. I think what we’ve decided to do was essentially pause work on additional clinical programs, as well as programs moving from preclinical into the clinic. And that’s really where I think the prioritization came from.

So we significantly meet the requirement for that loan facility, and that was actually just validated as we filed the K. Your first question around BD opportunities, I think as the former head of BD in my former career, I think we are always open to having conversations around BD. I think for us, what would be important is to — if we were to do a deal just to find a partner, that either has an opportunity for us to reach markets that we don’t necessarily have or to accelerate programs that we cannot. What I will say is there’s active discussions around potentially looking at opportunities for ex U.S.

territory type of deals that could accelerate clinical development and speed to market in certain parts of the world. But I think this is something that we’ll always kind of keep as dry powder. I think we will always look at ways to bring in nondilutive forms of capital while accelerating our programs. I think that’s always a prudent thing to do.

So a really good question. 

Operator

Our next question is from the line of Mike Ulz with Morgan Stanley. Please proceed with your question. 

Mike UlzMorgan Stanley — Analyst

Hey, guys. Thanks for taking the question. Just with respect to GAN, maybe you can just give us an update on your current thinking on the path forward there in the U.S. And in the past, you had mentioned analytic comparability as one of the potential scenarios there.

And I’m just curious if you’ve done that analysis yet or are you waiting to get feedback from the FDA before you move forward with that. Thanks. 

R. A. SessionPresident, Founder, and Chief Executive Officer

Thanks, Mike. Really good question. So really, I think it boils down to three scenarios in the United States with GAN. And ex U.S.

is kind of slightly different. I think there’s a clear pathway when you start to think about the EMA, which opens up the rest of the world who references the EMA. But particularly for the FDA, it boils down to three scenarios. I think two are higher probability.

One is lesser probability but certainly could always be a route that the FDA asks you to go. Scenario one would be if the FDA allows you to file with analytical comparability, essentially doing an analytical bridging study between the clinical material and the commercial-grade material. In order to, what we would say, increase the probability of success of this option, what we’ve decided to do was keep the manufacturer of this program at the same CDMO partner that manufacture the clinical program. We’re using the same cell line, same media, same downstream purification, same facility.

So these are — so essentially, it’s a like-for-like process. And we wanted to make sure we held these things constant because we wanted to be able to increase that probability. This what I would probably say would be probably not the FDA’s preferred route. We haven’t had that conversation with them.

But if you just look at the comp, then the closest comp to this would be the experience of Zolgensma. That would more align to option two. And I would say option two is probably our base case, and this is essentially what we’re planning for internally. And this would be somewhat a bridge between doing an analytical filing on analytical comparability and doing a new study.

This is essentially where you would dose a handful of patients under the current IND and protocol using the commercial-grade material. The goal would ultimately be to propose to the FDA filing a rolling submission, essentially filing the preclinical data first. That’s not changing. That’s all there.

Then starting to supplement the filing with the clinical data that’s already been generated, which we now have seven years’ worth of data, safety and efficacy data, that’s been generated that we’ve seen long-term durability, dose response, good safety, efficacy across the board, and then supplementing that data with new data generated with the commercial-grade material. What I will say is the engineering run for the commercial-grade material just completed, and the yields are phenomenal. And we’ve just kicked off our GMP runs of — for the validation batch, which is ultimately the commercial-grade material that will be released in Q3. So we’re actually quite excited that we’ve made significant progress along with our CDMO partner there.

The third scenario, which we think is somewhat unlikely and would be against the FDA’s guidance that they issued last year for the development of gene therapy in neurodegenerative diseases, is for them to go back and ask for an additional study. Here, the natural history is pretty well elucidated. We have three sources of comparatives. Each patient in the interventional trial rolled over from the natural history study.

So that’s the — so each patient acts as their own comparator. There’s also using the full cohort, natural history cohort, as a comparator. And because the natural history data was so extensive — because the history data was so extensive, you could actually find age-matched controls within that natural history cohort to act as a comparator. So we’re pretty fortunate that the level of robustness of the data, the long-term durability of the data, we now have pathological change where we actually see regeneration of nerve fibers from biopsies that were taken pre and post treatment.

We feel pretty good about the dataset that we’re going to go in and talk to regulators about. This should be extremely compelling. But those would be the three scenarios in the U.S. Ex U.S., we think this lines up perfectly for the conditional approval pathway based off the dataset today, and that’s going to be our conversation with the EMA regulators later this year.

Operator

Our next question is coming from the line of Jack Allen with Baird. Please proceed with your question.

Jack AllenBaird — Analyst

Hi. Thank you so much for taking the question, and congratulations on all the progress. I guess the first one, I wanted to stick in GAN and talk about TSHA-120. Maybe you could provide a little bit more context around the gating factors surrounding gaining regulatory clarity here.

Do you have a meeting on the calendar with FDA? Any comments around when you may have clarity around the time line in greater detail than mid-2022? And then I was just curious how the genetic testing program is going as well. Any comments you can make around early findings from that? And if you would consider presenting that data, I think it would be quite interesting to see a little bit more insight into the epidemiology of GAN as well. 

R. A. SessionPresident, Founder, and Chief Executive Officer

Thanks, Jack, for the questions. I think the easy answer is the current guidance is — for regulatory feedback is midyear 2022. So I think we’re going to probably just stop at that guidance without any further level of specificity. Obviously, as the agencies recover from COVID and meeting requests associated with COVID approvals, they’re continuing to approve the vaccines associated with that.

Getting meetings on the book and having those meetings actually stay on the book has been somewhat of an issue. But what I will say, I think we’re comfortable with the guidance of mid-2022. And so we’ll essentially stop there with any further detail around guidance. And once we have more specificity, happy to give that to you.

Or once we have that feedback in hand, happy to give that to you. As far as the genetic testing panel, this has actually gone quite well. And I think it’s — what was pretty interesting about some of the information that we’ve received is certainly, there’s more patients out there than I think the epidemiology that’s in the literature actually lets on. Just anecdotally, we had a pretty interesting situation where we were speaking with an investor on a Friday afternoon.

We get a call on Saturday. And essentially, the investor’s colleague, next-door neighbor, was diagnosed with GAN. So that kind of gives you a little bit of context. But I think now that the dataset is out there and I think having the positive dataset out there and the availability potentially of additional patients being dosed, patients tend to find you.

And this is just normal for rare disease, and this is what we’re seeing. 

Operator

Our next question is coming from the line of Kevin DeGeeter with Oppenheimer.

Kevin DeGeeterOppenheimer and Company — Analyst

Great. Thanks for taking our questions. Maybe a two-part question with regard to manufacturing. Can you provide an update as to whether the strategic refocusing has any impact on the buildout of in-house manufacturing capacity? And then kind of within the cash runway assumption, how should we think about capex and investment in manufacturing? 

R. A. SessionPresident, Founder, and Chief Executive Officer

Yeah, Kevin, thanks for the question. Obviously, manufacturing is strategically important to the company, particularly as we’re embarking onto, one, a validation run for commercial-grade materials; second, an extremely large indication in Rett syndrome. So what I’ll say is, again, manufacturing continues to stay strategically important to the company. We think it’s one of the aspects that sets the company up and differentiates the company from some of our peers out there.

And so that continues to remain a strategic focus. As far — and could you remind me of your second question? Oh, yes — 

Kevin DeGeeterOppenheimer and Company — Analyst

The second part was just, yes, within the cash runway guidance, how should we think about maybe cumulative capex or some other metric across that time frame? 

R. A. SessionPresident, Founder, and Chief Executive Officer

Yeah. I think, Kevin, we’re not going to provide additional guidance around what we’ve already provided around expense management and cash management, where cash extends until Q4 of 2023. But I think, again, to just answer your question, CMC for a gene therapy company, and we continued with our history, understanding where the bulk of the management team and board came from, controlling your own destiny remains a key strategic focus for the organization. So I think that’s where we’ll probably stop from a guidance perspective. 

Operator

Thank you. Our next question is from the line of Gil Blum with Needham & Company.

Gil BlumNeedham and Company — Analyst

Hello. Can you hear me?

R. A. SessionPresident, Founder, and Chief Executive Officer

Yeah, we can hear you.

Gil BlumNeedham and Company — Analyst

OK. Maybe just kind of general question about Rett here. So because it’s a relatively larger indication, would you also expect the studies to be larger or more expansive to that account? Thank you.

R. A. SessionPresident, Founder, and Chief Executive Officer

Hi, Gil. That’s a very insightful question. And I think as you can — the larger the opportunity, obviously, the larger the study. I’ll pause and let Suyash answer.

But I think the short answer to your question is yes. And I think when you start to look at the strategic prioritization, this is one of the reasons why we did — we’ve done what we’ve done, to put ourselves in the best position in order when we have Rett data, to position the organization broadly. Understanding the development cost for Rett both on the clinical side but also on the CMC side are going to be quite extensive. But I’ll stop there and let Suyash chime in.

Suyash PrasadChief Medical Officer and Head of R&D

Sure. Great questions, Gil. And essentially, you’re right. I want to say that the study is going to be big.

And what I will say is that extensive trial program as a whole is going to be bigger. And it’s bigger for two reasons really. First of all, it is a huge market opportunity, as you’ve already heard. And there’s also a little bit more focus on the safety matters with regard to Rett given the fact that there’s a risk of overexpression of MECP2.

And so it will be a little bit more cautious, you could say. That’s why as a whole, we’re going to start our clinical trial. As you all have heard from earlier this week, we now have a loaded CTA calendar, which we’re very excited about, and ready to start dosing patients. As a whole, we’re going to start with an adult study, primarily safety, looking at some preliminary efficacy.

After those a handful of adults, we’ll then move into a pediatric girls study where the bulk of the patients were better and where we think that the greatest opportunity for improvement will be, although we think all patients with Rett with improve regardless of age. And then shortly after that, we will also start a pediatric boys study, which is a somewhat unusual thing to do given that there are only a small number of boys around. But the boys, you’ll probably remember, are — have no MECP2. So obviously, they’re very severely affected.

The vast majority are [Inaudible]. A handful of them survived. So there may then be only 200, 300 boys in the world with it. But we’re going to do so kind of rescue study there and demonstrate an improvement.

And of course, because they have no MECP2, you’re not so worried about overexpression toxicity in these boys. It could actually provide that potentially expedited path for conditional approval. So that’s how we’re approaching the Rett situation as a whole. 

R. A. SessionPresident, Founder, and Chief Executive Officer

Yeah. The only thing that I would add to what Suyash just mentioned, when you start to think about the Rett boys, not only do they offer an accelerated pathway to an approval just because of the nature of the phenotype, the biology of the boys are quite similar to the biology of the animal models that we have for Rett. Essentially, the industry-standard animal model for Rett is the knockout mouse model. Essentially, that model has no MECP2.

And that’s basically what we’re seeing in the boys and the biology for their disease. And so as Suyash mentioned, there really is less of a concern around overexpression. But I think when you start to look and correlate the IND-enabling pharmacology studies 1:1, we’re seeing at multiple age groups a significant improvement across a number of hosts of functional outcomes, respiratory outcomes, motor function, and a number of other functional assessments. And again, when you even dose earlier in the neonates, we’re seeing a normalization of survival or preliminary data suggests a normalization of survival.

So this gives us a lot of confidence that the opportunity and, really, our goal is to not leave a patient behind here in this population. It’s a large indication. Just associated with the girls, we’re talking about 350,000 patients worldwide. So it’s a massive indication, it’s a massive indication.

But for us, I think it’s more important to make sure that all patients are addressed. 

Operator

Our next question comes from the line of Laura Chico with Wedbush Securities. Please proceed with your question.

Laura ChicoWedbush Securities — Analyst

Hey, good morning, guys. Thanks very much for taking the question. I guess I wanted to circle back on the cash runway. And with the changes, I just wanted to clarify how long the cash runway was extended.

And as it relates to the GAN program, I just want to understand the base case scenario you have around 120. And you walked through the options there, R.A. But I guess how would cash runway change if we had to go through kind of that extreme scenario where there was an additional study requested? Thanks very much. 

R. A. SessionPresident, Founder, and Chief Executive Officer

Thanks, Laura. I’ll take your second question first because it’s top of mind. So when you start to think about if the FDA came back with an option of doing a pivotal study in GAN, just because of the patient population, it’s to be a pretty small study. We would essentially roll over patients that are currently in the natural history study.

There’s about 50-plus patients in the current natural history study, of which about 40 of them haven’t been dosed. So the patients are there. So there is no kind of need to go search for patients, so you wouldn’t have to do some type of big patient-finding opportunity. So — but ultimately, the cash runway would be really minimally impacted.

I think when you start to think of clinical development for gene therapy trials, these trials are relatively small and the cost associated with conducting these trials are relatively small. The big cost is associated with the production of GMP manufacturing, right, and the use of external third parties to do that, which is what makes having your own manufacturing facility still strategically important because just, one, being able to get a slot at a high-quality manufacturer and the cost to do that are pretty high. The difference between scenario one, which would be to do analytical comparability, the base case which would be to dose a few more patients under the current protocol with commercial grain material once it’s available; and the third scenario, which if you had to do another complete study. The costs are, I would say, from scenario two to three are pretty much the same because you’ve already embarked on the production of GMP material that’s commercially validated.

So your commercial grade material. That’s where the big costs are. So it really would have minimal to no impact on cash runway, the difference between, honestly, scenario one, two or three because you’re already doing the big cost impact, which is manufacture of commercial-grade GMP material. So that’s your — that was your second question.

Your first question was around the extension of cash runway. I think we previously guided to cash being into the second half of 2023. We essentially have been fortunate to extend cash runway by quarter into 2020 — into Q4 2023. 

Operator

Our next question comes from the line of Yun Zhong with BTIG. Please proceed with your question.

Yun ZhongBTIG — Analyst

Hi. Good morning. Thanks very much for taking my question. So on the Rett Syndrome, I assume it’s a dose-finding study.

So I was curious how are you going to — or what kind of markets will allow you to decide that you are getting close to the optimal dose? And also on the efficacy readout, any potential signal for efficacy? And I think we previously talked about this potential biomarkers and the EEG be one of them. And just curious, would that be included in the data readout by year end, any additional markets?

Suyash PrasadChief Medical Officer and Head of R&D

Sure. Let me make a couple of comments. The two doses — you’re right, the [Inaudible] study in adult females with Rett, the initial start of this is the five in 14 total vg dose, and we’re provisioned to escalate up to the 1.0×1015 total vg. Now I think the most important thing here is that we have an incredibly robust preclinical practice.

It’s what allowed us to have the CTA open. And we’ve had a lot of back forth with the regulators on some of the details. And the preclinical practice, the idea enabled preclinical practice was designed around our three studies built on many, many years of work that Steven Gray and Sarah Sinnett were involved in. So the most important study for dose-finding perspectives are pharmacology study, which we ran in 252 mice, with Rett syndrome, wild-type mice, with 12 cohorts — sorry, 21 cohorts.

And we looked at a number of different doses, a number of different aged time points of dosing mice and the whole spectrum of parameters. All of this translate nicely to clinical measures. For example, look at the gait of these mice, important form factors modeled around their breathing, and a whole host of other assessments. From that particular study, we’re able to elucidate the minimally impacted dose.

And then on top of that, we also ran our toxicology studies, both in rats and NHPs. And the important data was, of course, the NHP data, biodistribution data. And importantly, we found that with an elevated dose, all falls over this clinical starting dose. We actually have definitely clean tox.

And our toxicology had no adverse findings. And we had very high levels of DNA strengthened by distribution, but correspondingly low levels of mRNA, so mechanistically showing the down regulation is working. We expect the IND for the pharmacology study and the toxicology study with no observable adverse event level. You can actually hone in on a very good starting dose.

And as I said, some of this is five in 14, and we’ve got the 1.0×1015, none of those showed any appreciable toxicity, and we expect both to be efficacious. That’s how we select the dose. In terms of after measures, we went through a whole host of after measures. You do know, of course, if there are no official, well-known, well-understood biomarkers and serum in the CSF, we are looking to a whole of host some exploratory biomarkers.

We’re looking on EEG as a potential biomarker as well and a whole host of different clinical endpoints, the RSBQ and CGI, the Rett severity score, as well as broader actual measures, such as the brainstem function, respiration, looking at seizure frequency, how many seizures, what previously — what triggers them. So we’re going to be guiding our dose selection on the answers of a safety signal and just in general, progress from a clinical perspective. As I say, EEG, we’ll be using [Inaudible] biomarkers, they’re not for decisions around the biomarkers. These are not well understood yet. 

Operator

Our next question comes from the line of Silvan Tuerkcan with JMP Securities. Please proceed with your question.

Silvan TuerkcanJMP Securities — Analyst

Good morning. Congrats on all the progress. I just had two quick questions, please. Could you run me maybe in more granularity through your GAN base case in terms of getting this into — commercial material into handful of patients? How much would be a handful? And when could this start? Would it makes sense to start right now? Or do you need to wait for your validation run in the third quarter? So how much time to filing? And then my second quick question would be on the CLN7 program and are you going ahead with the first-gen construct? Do you think that’s good enough? Or do you just want to get some clinical experience no matter what with this program? Thank you for taking my questions. 

R. A. SessionPresident, Founder, and Chief Executive Officer

Thanks, Silvan. Good morning. Good question. So starting with the first around the availability of commercially — commercial GMP material, commercial-grade GMP material on GAN.

As I mentioned before, we’ve actually just completed our second engineering run. This was — the first with a small-scale engineering run as a CDMO partner that went beautifully. The second was the definitive engineering run at scale that also went extremely well. This is — we’re actually quite fortunate.

GAN and Rett are actually our two highest-producing, highest-yielding products. And so one being on a pathway for regulatory discussions around what the approval pathway looks like and the second just being a massive indication, I think this just really lines up nicely with how we’re thinking about prioritizing our efforts this year. So we’re actually quite excited about that. Our GMP, the definitive GMP run for the commercial-grade material just kicked off.

And we expect that material to be available in Q3. This would either be the material that would support — if we’re able to do analytical comparability and the agency agrees with that that would be scenario one, which would be the best-case scenario. This would be the material that would support that BLA. I still think even in the best case, it would be more of a rolling submission because there will be still some additional work from an analytical perspective that would need to be completed.

From a base case, which we consider scenario two, kind of the base case, you would still need this material to be released in order to commence dosing a few more patients under the current protocol. And so what you would do for scenario one, scenario two, and scenario three really are — really, the same activities. You need commercial grade material. You’re going to either under scenario two and three, need to dose additional patients with commercial grade material.

Under scenario one, you need the commercial-grade material in order to support the BLA in order to eventually commercialize the product. So all the activities are the same. But from a timing perspective, we expect that material to be released in Q3 of this year. But as I mentioned, the two engineering runs, small-scale and large-scale engineering runs kicked off and completed quite nicely.

And we’ve recently kicked off the commercial-grade GMP run. So we’re pretty excited about the progress there, hence the prioritization. 

Operator

Our next question is from the line of Kristen Kluska with Cantor. Please proceed with your question.

Rick MillerCantor Fitzgerald — Analyst

Good morning. This is Rick on for Kristen. Thank you for taking my question. In terms of the prioritized programs announced today, could you please talk a little bit about the potential for grants or other nondilutive funding opportunities around these indications? For example, we understand that a federal funding bill was recently passed supporting funding for Rett Syndrome research.

Thank you.

R. A. SessionPresident, Founder, and Chief Executive Officer

No. It’s a really good question. I think for Rett, obviously, Rett and GAN are squarely within the activity that we have prioritized, and that’s where the bulk of our R&D investments are going. But certainly, we always look for additional opportunities for nondilutive financing, either that’s through grants, government grants, advocacy grants we’ve done in our history.

We just haven’t spoken a lot about them. But what we’ve done in the past is collaborate very closely with the advocacy groups where they funded a lot of the early proof-of-concept work. And we’ve kind of taken a program over once we’ve gotten to a definitive animal proof of concept in order to do the IND-enabling tox studies and the IND-enabling pharmacology studies and kind of win the big dollars that you need associated with GMP manufacturing before you go into a clinical trial. So these things are always top-of-mind, and in our history, I think we’ve always looked for ways to bring in nondilutive forms of financing, particularly even more important in a situation where the market, from a macro perspective is a little bit uncertain, right? Geopolitical down sector and a number of other issues that are macro, that aren’t specific to the company, including looking at potential business development opportunities, particularly with programs that we see broad therapeutic potential but unfortunately, just haven’t hit our level of prioritization.

Now again, we always have the opportunity to revisit that if and when situations change. But today, what I would say for clarity, the company is focused on the guidance that we’ve given you guys today. So that’s just — that’s where we are. But I think to your question, we always look for nondilutive ways along with our partners at advocacy, along with our partner, the UT Southwestern for nondilutive funding.

I just wanted to answer, Silvan, the second question. And I apologize, Silvan, for skipping over and around CLN7. To clarify, the CLN7 programs have actually gone quite well. As Suyash mentioned, we recently dosed the fourth patient, which is the third patient dosed at 1.0×1015, which is the highest dose ever given intrathecally in a gene therapy trial.

Patient safety was reported at World Symposium earlier this year. These spaces continue to do well. And ultimately, I think you guys have heard me say this before, if it’s not broke, don’t fix it. And so we’re going to continue to focus solely on the first-generation construct because, ultimately, that’s going to allow for a faster pathway to registration.

So that’s really what’s kind of led us there. But future development will be focused solely on the first-generation construct. Thank you both for the questions. 

Operator

Thank you. Our next question is from the line of Eun Yang with Jefferies. Please proceed with your question.

Eun YangJefferies — Analyst

Thank you for taking my question. So I have a question on GAN. So for the full end of last year, you mentioned that — I think you’re meeting with the ex-regulatory — ex-U.S. regulatory agency scheduled in January.

So have you met with them? I know you are not going to provide an update on [Inaudible] this year but just wanted to check if you have met with them. And also in the U.S., you talked about three scenarios for some time. It sounds like option two could be a likely option when you meet with the FDA. If it’s for option two, what would be the timing for BLA filing? I think in the past, you mentioned them around mid-2023.

So I want to get your updated view on that. And lastly, R.A., you mentioned that your cash runway has been increased by one quarter. So should we really think about the reduction in workforce by 35% leads to one quarter extension in the cash runway? Thank you. 

R. A. SessionPresident, Founder, and Chief Executive Officer

Eun, thanks for the question. So starting with your first question around regulatory, we have previously guided that we did conduct a meeting in late January with an ex-U.S. regulatory authority around scientific devices for our GAN program. We’re still awaiting formal meeting minutes from that program or from that meeting.

And once we have all of the formal meeting minutes both from this regulatory meeting, as well as the regulatory meetings that will be scheduled with the U.S. agency and other agencies, we’ll make sure to summarize those and provide that guidance and update that guidance once we have the formal feedback. But it would just be premature for me to speak kind of outside of school about meeting them. Certainly the tone was a good meeting.

It was a long meeting as they were quite interested. The data, obviously, as we laid it out, is compelling. But again, I want to make sure that we have final meeting minutes in hand before we provide any additional feedback on that. Around GAN specifically, I think you’re absolutely right.

We kind of coalesced around scenario two as the base case, and that’s kind of the case that we’re planning for internally. What I would say is the difference between scenario two of building a fewer patients under — a handful of patients under the current protocol and scenario three is doing a second study, it’s probably six to eight months. There’s not much of a gap really between either one of those scenarios. The reason for that is because all the patients are identified.

You’re not going out to have to identify patients. This would essentially be a rollover from — this would essentially be a rollover from the natural history study, as I mentioned, there’s already 50-plus patients in the natural history study, of which only 14 of those patients have been dosed. So you could think about 40 or so of those patients haven’t been dosed, and we continue, as I mentioned, to identify patients on an ongoing basis quite successfully. So from an enrollment perspective, you really won’t have an issue from a timing around enrollment.

More so, the timing is associated with the availability of commercial-grade material. And then as I mentioned, that material would be available in Q3. So if you would take scenario two, which is very similar to the Zolgensma scenario from our previous life, where essentially the FDA-approved Zolgensma on the basis of the original nationwide Zolgen study, and then those original patients, I think it was close to about 10 patients that were dosed in that study. They then allowed AveXis, Novartis at the time, to supplement the data set with data from the pivotal study with their commercial material that was being delivered from Liberty Bill, which was the commercial manufacturing facility located up in Chicago.

And so this would essentially be the pathway that we are kind of considering as the best case because it’s the best comps that we have out there. This is a rare pediatric, life-threatening, neurodegenerative disease where there’s no therapeutic alternative. In the case of Zolgensma, there was actually a therapeutic alternative and an approval ahead of that in SPINRAZA. In the case of giant axonal neuropathy, there’s nothing.

And so certainly, in our conversations with advocates, in our conversations with KOLs, we pressure tested our thinking, and we think this would be the optimal approach to potentially to go into. Now we’re going to go in and do our best to convince the agency around scenario one. But I think realistically, I think what we’re going to do is plan for a — somewhat of a mid-case, which would be scenario two. That would allow us to either initiate a rolling submission at the end of this year or the beginning of next year and, ultimately, lead to an approval either late — and when I say late, end of the year 2023 or early 2020 in the U.S.

Obviously, the pathway in Europe is quite different. We feel strongly that we meet the guidance around the conditional approval pathway. And that’s going to be our going in conversation with the EMA regulators is really how to accelerate registration options for this program under the conditional approval pathway. And so that’s going to be our goal.

And so we want to be in the position if the regulators agree, which again, with the data set that we have in hand, we think there’s a strong possibility to initiate a rolling submission by the end of this year. 

Operator

Thank you. Our next question is from the line of Sami Corwin with William Blair. 

Sami CorwinWilliam Blair — Analyst

Hey, guys. Thank you for taking my question. For the Rett study, will there be different outcome measures for patients depending on their age or disease stage? And then can we expect any data this year from the CLN1 or CLN7 clinical trials? Thanks.

R. A. SessionPresident, Founder, and Chief Executive Officer

Hey, Sami. Good morning. Thanks for the question. Could you repeat your first question? I’m sorry, we couldn’t hear you.

Sami CorwinWilliam Blair — Analyst

Yeah. Will there be different outcome measures for patients in the Rett trial depending on their disease stage?

R. A. SessionPresident, Founder, and Chief Executive Officer

It’s a really good question. Suyash, do you want to tackle that first?

Suyash PrasadChief Medical Officer and Head of R&D

Yeah. In general, yes and no, basically. We’re going to be looking at similar growth buckets of efficacy measurements regardless of age. So we’ll be looking at specific Rett assessments, such as the RSBQ, such as the Rett behavior assessment, the hand expression scale.

We can look at certain seizure measurements, EEGs for example, seizure signs. We’ll look for respiratory assessments, respiratory distress index, sleep apnea, etc., communication assessments, the ORCA quality assessment, plus a whole host of different biomarkers.

Operator

Thank you. Our next question is from the line of David Hoang with SMBC.

David HoangSMBC Nikko Securities — Analyst

Hey, thanks for providing update and taking my question. So I just had a few. Again, going back to the base case for GAN and the regulatory path there, do you have any sense about how many additional patients FDA might ask you to dose? And then in terms of the follow-up on those patients who received the commercial-grade material, what do you exactly need to report? Is it just safety and PK data? Or do you need to follow them and get some efficacy data as well?

R. A. SessionPresident, Founder, and Chief Executive Officer

Yeah. I think it’s a really good question. And David, unfortunately, you guys cut out a little bit. So we’ll go back and answer Sami’s question after we answer your question, David.

But your question was really, I think it boils down to what do you think you’ll need to show from an efficacy perspective around the commercial-grade material and how long do you think the follow-up would be around what you would need in order to prove comparability. Well, I’ll tell you the best comp in this again would be in Zolgensma. Zolgensma, the FDA allowed us previously to use the CHOP INTEND as a really nice biomarker around activity and kind of comparability between the original clinical trial material and the commercial-grade material. Because the CHOP INTEND actually pretty went up — it went up pretty uniformly within the first 30 days across all patients.

So you know you were getting really good target engagement. I don’t think that’s too dissimilar here where we’re using the MFM32, which is similar in a sense as the CHOP INTEND for older patients. And I think when you look across the entire data set, you do see a really nice kind of stabilization and improvement in disease as compared to the natural history very shortly thereafter dosing. And so I think using our previous experience in Zolgensma, I don’t think that that is far removed.

Now what I will say, this is speculation because we haven’t had the discussion, [Inaudible] what they’re going to ask for. And certainly, we’re going to do what they ask us to do. But I think what we’ll ultimately do is lean this sense of safety database that we [Technical difficulty]

Operator

Please standby. We’ll resume with your answer in a moment, Mr. Hoang. Speakers, you may continue with your answer with Mr.

Hoang. Please standby, our question-and-answer session will resume momentarily. Please remain on the line. Thank you.

We can hear you now. Please continue. 

R. A. SessionPresident, Founder, and Chief Executive Officer

Operator, so we’re going to give this another go. We just dialed in. Just let us know when we dial out and we just have the phone line available, and we’ll just pass the phone around.

Operator

I can hear you. You can be heard in the conference again now. We still have Mr. Hoang on the line with his first question.

R. A. SessionPresident, Founder, and Chief Executive Officer

Perfect. Perfect. David, sorry about this. We’re just having some technical issues in the room.

But to your question, I was just basically correlating our experience with Zolgensma and the approval pathway to Zolgensma and what the FDA asked us to do as we compare to trying to use that experience for GAN. So the question was really around what was the extent of the follow-up. The extent of the follow-up in the Zolgensma was really using the CHOP INTEND as they compare to a former comparator for clinical comparability of the commercial-grade material. And so we’re fortunate to have a similar assessment in the MFM32, which is essentially the CHOP INTEND for the older kids.

And what we’re seeing is pretty early, a nice separation between patients that are in the interventional trial compared to the natural history study. And so for us, we think that that could be a useful example and a comparator to provide to the FDA because you actually see a nice separation relatively quickly. What I’ll also say is when you start to look at the long-term safety and durability, the patient that we have the most efficacy data on received the lowest middle doses with the dose of 1.2E to the 14. And I think this patient, if they didn’t receive the intervention would have probably succumbed.

Because where this patient started was actually one of the lower scores on the MFM32 and we’ve essentially seen a really nice stabilization of the disease now going out five years. So I think with that sort of totality of data, along with the pathology data from the biopsy, along with having a validated instrument that’s been used in regulatory approvals before in MFM32. I think we have a really compelling argument to be able to go in and basically shoot for the minimum amount of follow-up that’s possible, really just to validate that we have active drug. That could be somewhere between [Technical difficulty] 

Operator

Ladies and gentlemen, please standby while we switch the speaker’s line. Speakers, please continue on your second line. Please go ahead.

R. A. SessionPresident, Founder, and Chief Executive Officer

Yes. We have to disconnect the other line. Yes. So I think I answered the question ultimately.

I think I was just providing some additional commentary. So I think I answered David’s question. And again, sorry, for the technical difficulties there.

Operator

Thank you. Please stand by while we resume with the line of Sami Corwin. Sami, please go ahead. 

Sami CorwinWilliam Blair — Analyst

Hey, guys. Yeah. I think you were just going to answer my question on if we can expect any data from CLN1 or CLN7?

R. A. SessionPresident, Founder, and Chief Executive Officer

Thanks, Sami. Yeah, so we’ve already presented data earlier this year on the CLN7 program, that was on the first three patients that were dosed, the first being 5B to the 14. The next two that were presented was at the 1E to the 15 dose, and we’ve mentioned that an additional patient was treated at 1E to the 15. And so we’ve already reported data on that program, and we continue to follow those patients.

On CLN7, what we’ve decided to do is to not guide to the availability of clinical data, but to say that we continue — we’re kind of morphing this program into — and limiting enrollment to a proof-of-concept study kind of a little bit different of a strategy from kind of a fast pathway to registration type of strategy. And so we’ll guide to data later this year on the CLN1 program. 

Operator

Thank you. Our final question comes from the line of Yanan Zhu with Wells Fargo. Please proceed with your question.

Yanan ZhuWells Fargo Securities — Analyst

Hi. Thanks for taking my question, and congrats on the initiation of the Rett Syndrome. Program, clinical trial. So my question is on the GAN programs data.

Because I think R.A., you mentioned about age-matched controls. I think so far, the MFM32 data you presented is mainly the overall natural history control cohort. So I was wondering what does the age-matched controls look like? Because I think you mentioned you have enough patient data there to do the specific age match. And also, is that part of your conversation or package with your regulatory interaction?

R. A. SessionPresident, Founder, and Chief Executive Officer

Yanan, thanks for the question. So essentially, what I’ll say is those analysis are ongoing. But I think what’s important here, we have previously showed data that from the previous doses of patients pretreatment decline and their post-treatment stabilization. That’s data that we actually shared last year when we acquired the program.

The data that we shared this year was essentially a comparison from the full cohort of natural history that basically shows an 8.07 decline compared to the cohorts’ experience depending on that particular dose cohort. That’s the data that we’ve shared recently. And now the analysis around age match controls, which is a little bit more extensive is ongoing but I think you’re absolutely right, this just lends itself to the robustness of the data itself. The fact of the matter that we have access to natural history data that offers three levels of control, is extremely — it’s extremely compelling.

So when you start to look at the data set that we’re going to go in and have conversations with the regulators, you’ll have natural history data, three levels of control, biopsy data, functional data across a number of meaningful clinical functions, including MFM32, including visual acuity, pathology data from the biopsy but also retinal nerve fiber thickness data, as well as a whole host of sensory endpoints that we haven’t presented to The Street yet. So we feel, honestly, I think if you would ask Suyash, and I’m only answering this because of the technical difficulties that we had. If you ask Suyash, he would probably tell you that he’s never gone into a conversation with the regulator with this wealth of data before. And I think this gives us a lot of confidence around the conversation with the regulators.

And so that’s essentially what I’ll say. The level of comparison from the natural history, the wealth of endpoints that were collected, the pathology data that we have in hand, and what that shows us really lends itself and is why we feel so confident about our conversations and, to be quite honest, why we made the decision around prioritization today. 

Operator

Thank you. At this time, we’ve reached the end of the question-and-answer session. And I’ll now turn the call over to Mr. Session for closing remarks.

R. A. SessionPresident, Founder, and Chief Executive Officer

Yes. Thank you, operator. And first and foremost, we just want to apologize for any other technical difficulties. I think we got through probably about 80% of the questions before that started to kick in.

So hopefully, our colleagues from the analyst community found this helpful, as well as the broader community, but we really appreciate you guys joining us this morning. I think the way we’re thinking about 2022 is a year of focus. It’s a year of operational efficiency, and it’s a transformational year as we potentially transition the company from now, and I say this every year, which is actually quite nice, now from a clinical-stage company to a late-stage clinical company into a registration company preparing for our first commercial launch. And so that is an important level of transition.

Obviously, we’re doing this in uncertain times from a capital markets perspective. But I think the changes that we’ve made today have — and announced today really set the company up to be in the best possible position for when we have both data in hand from our Rett Syndrome program and feedback from regulators around our GAN program, and it put us, again, in a position of strength. So we really want to thank you guys for joining us today and hope you all have a wonderful day and a wonderful rest of the week. So thank you. 

Operator

[Operator signoff]

Duration: 81 minutes

Call participants:

Kimberly LeeChief Corporates Affair Officer

R. A. SessionPresident, Founder, and Chief Executive Officer

Suyash PrasadChief Medical Officer and Head of R&D

Kamran AlamChief Financial Officer

Elizabeth WebsterGoldman Sachs — Analyst

Joon LeeTruist Securities — Analyst

Mike UlzMorgan Stanley — Analyst

Jack AllenBaird — Analyst

Kevin DeGeeterOppenheimer and Company — Analyst

Gil BlumNeedham and Company — Analyst

Laura ChicoWedbush Securities — Analyst

Yun ZhongBTIG — Analyst

Silvan TuerkcanJMP Securities — Analyst

Rick MillerCantor Fitzgerald — Analyst

Eun YangJefferies — Analyst

Sami CorwinWilliam Blair — Analyst

David HoangSMBC Nikko Securities — Analyst

Yanan ZhuWells Fargo Securities — Analyst

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