Taysha Gene Therapies (NASDAQ:TSHA) Q4 2021 Earnings Conference Call March 31, 2022 8:00 AM ET
Company Participants
RA Session II – President, Chief Executive Officer & Founder
Kimberly Lee – Corporate Affairs Officer
Suyash Prasad – Chief Medical Officer & Head, Research & Development
Kamran Alam – Chief Financial Officer
Conference Call Participants
Elizabeth Webster – Goldman Sachs
Joon Lee – Truist Securities
Mike Ulz – Morgan Stanley
Jack Allen – Baird
Kevin DeGeeter – Oppenheimer
Gil Blum – Needham and Company
Laura Chico – Wedbush Securities
Yun Zhong – BTIG
Silvan Tuerkcan – JMP Securities
Rick Krause – Cantor Fitzgerald
Eun Yang – Jefferies
Sami Corwin – William Blair
David Hoang – SMBC
Yanan Zhu – Wells Fargo
Operator
Welcome to the Taysha Gene Therapies, Fourth Quarter and full-year 2021 financial results and corporate update. At this time, all participants are in listen-only mode. Following management’s prepared remarks, we will hold a brief question-and-answer session. As a reminder this call is being recorded today March 31st, 2022. I will now turn the call over to Dr. Kimberly Lee, Chief Corporate Affairs Officer. Please go ahead.
Kimberly Lee
Good morning and welcome to Taysha’s fourth quarter and full-year 2021 financial results and corporate update and conference call. Joining me on today’s call our RA 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 31st, 2021. The 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 of timing and results of clinical trials for a product candidate. Our expectations regarding the data necessary to support regulatory approval of Taysha 120. The regulatory status and market opportunity for our clinical programs, as well as patients manufacturing plants. This call may also contain forward-looking statements relating to Taysha’s growth and future operating results, discovering development and product candidates, strategic alliances, intellectual property, cash runway, and improvement limitation, 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 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 are dependent upon strategic alliances and other third-party relationships. Our ability to obtain patent protection for discoveries, limitations imposed by pans owner controlled by third-parties.
And then requirement of successful funding to deduct our research and development activities. For listened 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, as so as maybe required by applicable securities law. With that, I’d now like to turn the call over to our President, founder and CEO, RA Session II. RA?
RA Session II
Thank you, Kim. Good morning and welcome everyone to our call. 2021 was a year of accomplishment 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 programs. Suyash, please go ahead.
Suyash Prasad
Thanks RA. Recently, we reported positive initial clinical data for GAN GM2 gangliosidosis and CLN7 disease further validating the therapeutic potential platform in multiple diseases of the central nervous system. Let’s begin with Taysha 120 for the treatments of GAN. Taysha 120 is the first gene therapy to be interested equally dosed, and is this currently being evaluated as approximate groundbreaking historic dose escalation clinical trial at the NIH, under the leadership of the principal investigator, cost and dominant.
We recently reported positive clinical efficacy on safety data for the high dose cohort of 3.514 total VG, as well as long-term safety and durability data across all therapeutic doses. Treatment with Taysha 120 achieved a clinically meaningful on statistically significant slowing or halting of disease progression seen in the highest price cohort of 3.58014 total BJ on cross-sold therapeutic dose cohorts. At the highest dose, Taysha 120 demonstrated clinically meaningful and statistically significant improvements in 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 main change from baseline and MFM32 score by year three compared to the estimated natural history decline of 24 points. These long-term data confirmed with disease modifying effect on sustained your ability of TSHA-120. Notably, no biopsy data, pre and post-treatment with TSHA-120, provided evidence active regenerations, of fibers thereby demonstrating pathological improvement to complement the clinical benefit saying.
In addition, preservation of visual acuity as measured by the lock Moscow was observed. And this was in conjunction with improvements in retinal nerve fiber last thickness as assessed by optical coherence tomography. So, no significant safety issues and no increase in adverse events at high doses. All adverse events relate to immunosuppression of study procedures were comparable to other Gene therapies and trends into night shop. 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 the states that’s the most comprehensive Gene therapy dataset in GAN, offering TSHA-120 a potentially de -risk regulatory path. We believe this program currently meet the 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 Drugs 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’s also includes collaborations with Hereditary Neuropathy Foundation and the Charcot-Marie-Tooth Association Centers of Excellence, as well as healthcare professionals on patient advocacy groups to increase access to genetic testing. Turning to Rett syndrome, TSHA-102 is the first and only Gene therapy and clinical developments for Rett syndrome and is designed to deliver MECP2 transgene using our novel miRARE platform, or micro RNA Responsive Auto-Regulatory Element platform. This technology is exclusively licensed to Taysha and developed by Doctors [Indiscernible] and Steven Gray of UT Southwestern Medical Center. MRI is designed to provide a sophisticated regulation of transgene expression, genotypically on a cell-by-cell basis, delivering controlled expression, 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, Quebec, Canada has been selected as the initial clinical sites under the direction of Dr. [Indiscernible], principal investigator. We also announced positive preclinical data that supported the CTA acceptance, including the pharmacology study and reps knockout mice assessing the efficacy of TSHA-102, and the six-month GLP toxicology study in non-human primates, exploring the budgets attributions and mechanism of action of TSHA-102.
Taysha 102 has a robust preclinical data package that supports and validates the ability of miRARE to safely regulate trends Gene expression. Data from the CTA naive and pharmacology study in last models syndrome demonstrated that miRARE regulated trends Gene expression, improved survival, respiratory function, and motor of function assessments across multiple dose levels.
A onetime intrathecal injection of Taysha 102 significantly increased survival at all dose levels with a mid to high doses improving survival across all age groups compared to vehicle treated controls. Treatment with takes you want to significantly improved body weight motor function on respiratory assessments and MECP2 knockouts mice. An additional study in the [Indiscernible] is currently ongoing with preliminary data suggesting normalization of survival.
Positive CTA enabling [Indiscernible] GLP toxicology data, non-HP reinforced Taysha launches favorable safety profile across all dose levels tested, including doses up to four fold above the Brazilians clinical stocks index. These data supported by distribution as reflected by DNA copy number in multiple areas of the brain on sections of spinal cord. Perhaps most importantly we observed correspondingly low levels of MRNI across multiple tissues.
This indicates the MRAP down regulation is appropriately minimizing a trends gene-expression from the construct in the presence of endogenous MECP2 in these wild-type NHP as expected. Let me repeat that. High levels of DNA in target tissues, meaning that there’s good distribution of drug from NHP conjection. But low levels of MRNA, meaning that the down regulation by the MRAP is working well to minimize any toxicity.
Indeed, low toxicity from trenching expression was observed, which was confirmed by functional evaluations, demonstrating no detrimental change in near behavioral assessments, and histopathologic evaluations demonstrating no adverse tissue findings on 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 pre -clinical safety and efficacy data will be presented at the International Rett syndrome Foundation. Rett syndrome scientific meeting taking place April 26 to 27, 2022 and Nashville, Tennessee. Currently, there are no disease modifying therapies to treat over 350,000 patients, estimated the suffer from Rett syndrome worldwide. We’re excited to advance TSHA-102 as the first Gene therapy and clinical development for the treatments of this devastating neurodevelopmental disorder, and look forward to reporting preliminary Phase 1-2 clinical data by the end of the 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 HEXA gene, coding the alpha sub-unit, and the HEXB gene, coding for the beta sub-unit, in a one-to-one 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 by-market data in January for TSHA-101, demonstrating normalization to beta sub-units of Hexosaminidase A or HEXA enzyme activity in patients with multiple forms of GM2 gangliosidosis.
We shared data for two patients, including Month 1 and Month 3 analysis for patient with Sandhoff disease, and Month 1 analysis for patient with Tay-Sachs disease. Following one particular demonstration, TSHA-101 achieved HEXA enzyme activity of a 190% of normal at Month 1, and 298% at Month 3, in Patient 1 with Sandhoff disease, representing 38-fold on 58-fold above the presumed asymptomatic level of 5% of normal identified by natural history at Month 1 and Month 3, respectively.
Patient 2 with Tay-Sachs disease, achieved HEXA enzyme activity of 25% of normal at Month 1, which represented 5-fold 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 1 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’re continuing to monitor patients two and three. We do not intend to perceive further enrollment in the Phase one two trial at this time due to prioritization of programs that increase operational efficiency. But we will continue to follow the patients who were previously dosed.
Well, CLN7 we reported posted preliminary clinical safety data for the first-generation construct in CLN7 investment disease from the ongoing clinical trial in collaboration of UT Southwestern Children’s Health and children Medical Center Foundation. We recently dosed a 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 in particularly in humans with Gene therapy.
Dose escalation from 5E14 to 1E15 total VG was supported by the data safety monitoring board. Initial data for three patients supported a favorable tolerability, on safety profile with no major adverse events across doses. Further development of sale and seven 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 and GAM by mid-2022, and preliminary Phase 1-2 data for TSHA-102 and Rett syndrome by year-end.
Clinical developments of the first-generation constructs, the CLN7 remains ongoing with our existing partners. We will continue clinical development of TSHA -118 in CLN1 night in sale on one 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 Alam
Thank you. Suyash. This morning, I will discuss key aspects of our fourth 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, recent 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 non-cash 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 in consulting for regulatory and clinical studies.
In general, 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 31st, 2021, compared to $11.1 million for the full-year ended December 31st, 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 non-cash 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 efficacy activities. Net loss for the three months ended December 31st, 2021 was $50.4 million or $1.32 per share as compared to a net loss of $18.3 million or a $0.50 per share for the three months ended December 31st, 2020.
Net loss for the full-year ended December 31st, 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 31st, 2020. As of December 31st, 2021, Taysha had $149.1 million dollars 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 [Indiscernible].
RA Session II
Thanks, Kamran. This year we are focused on strategic pipeline prioritization initiatives for GAN and Rett syndrome. And our plan is 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 to patients and advocates who remain our motivation everyday 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?
Question-and-Answer Session
Operator
Thank you. At this time will now be conducting a question-and-answer session. [Operator Instructions]. For participants using speaker equipment, it maybe necessary to pick up your handset before pressing the star keys. So that we may address questions for as many participants as possible, we ask you to limit yourself to one question. One moment, please while we poll for questions. Thank you. And our first question comes from the line of Salveen Richter with Goldman Sachs. Please proceed with your question.
Elizabeth Webster
All right. 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 de -prioritize that program?
RA Session II
Hey, Elizabeth. Good morning. Hopefully, you can hear me okay. 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 on a fundraising perspective, I think it was really imperative to the company in the best possible position for when Rett data will 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 another look at prioritization. Once we see external factors stabilized somewhat, but I think this is really — this was extremely important to make sure where is that the company itself was put in the best possible position to preserve cash runway, but also value creation. Obviously, the focus on GAN, it’s 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 therapies in development where a lot of other companies haven’t made at 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 Lee
Hi, thanks for taking our questions. In addition to restructuring, would you also consider monetization of some of non-core programs via out-licensing or partnering? And then also our understanding is that the term loans from 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.
RA Session II
Good morning. Thanks for the questions. I’ll take the last question first, so I think as we stated, there will be a key focus on Dan and Rett syndrome, but we’re also going to be continuing development on CLN1, CLN7, and FLB 13, AE5. So in total, there’s five active programs. I think what we’ve decided to do with essentially pause work on additional clinical programs, as well as programs moving from pre -clinical into the clinic.
And that’s really where I think the prioritization came from. So we significantly meet the requirements for that long facility. And now with actually just validated, as we filed the K. Your first question around BD opportunities. I think the former head of BD in my former career, I think we were always open to having conversations around BD. I think for us, what would be important is too if we were to do a deal is 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 can not.
What I will say is there’s active discussions around potentially looking at opportunities for ex – U.S. territory types of deals that could accelerate clinical development and speed-to-market and certain parts of the world. But I think this is something that will always kind of keep as dry powder. I think we will always look at raise two ways to bring in non – dilutive forms of capital. Capital while accelerating our programs. I think that’s always a prudent thing to do. So really good question.
Operator
Our next question is from the line of Mike Ulz with Morgan Stanley, please proceed with your question.
Mike Ulz
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’d mentioned analytic comparablity 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.
RA Session II
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. have 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 through references the EMA, but particularly for the FDA, it boils down to three scenarios. I think two were higher probability, one is lesser profitability, but certainly could always be a route that the FDA asked you to go.
Scenario 1 would be if the FDA allows you to file with analytical comparability, essentially doing an analytical bridging study between the clinical materials 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 with keep the manufacturer of this program at the same CDMO partner than maybe back to the clinical program we’re using the same cell line same media, same downstream purification, same facility.
So these are — essentially it’s a like-for-like process and we wanted to make sure we held the thing confident because we wanted to be able to increase our probability. This is why we’d 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 and 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 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, following the preclinical data first. That’s not changing. That’s all there. Then starting to supplement the file and 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 in 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 Jeff completed, and the yields are phenomenal. And we’ve just kicked off our GMP run of — for the validation batch of 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 guidance, that they issued last year for the development of Gene therapy and 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 comparators. 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 cohorts, natural history cohort as a competitor. And because the natural history data was so extensive, you can actually find aged-matched controls. It was in 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 that 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 Allen
All right. Thank you so much for taking my questions and congratulations on all progress. I guess the first one I wanted to stick in GAN and talk about TSHA-120. Maybe you can provide a little bit more context around the dating factors surrounding getting regulatory clarity here. Do you have a meeting on the calendar with FDA and any comments around when you may have clarity around the timeline 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 would be quite interesting to see a little bit more insight into epidemiology of GAN as well.
RA Session II
Thanks Jack for the question. 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 further level of specificity. Obviously, as the agencies recover from COVID and meeting request associated with COVID approval, they’re continuing to approved vaccines associated with that. Getting meetings on the both been having those meetings actually stay on the book is has been somewhat of an issue, but what I will say, I think we’re comfortable with the guidance mid 2022.
And so we’ll essentially stopped 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, there’s we’ve actually gone quite well and I think it’s what was pretty interesting about some of the information that we’ve received as it’s certainly. There’s more patients out there than I think the epidemiology that’s in the literature actually lead on just anecdotally.
And 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 that I think now that the dataset is out there. And I think having the positive dataset out there and the availability of potentially of additional patients being dosed, patients tend to find you and this has 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 DeGeeter
Okay. Great. Thanks for taking our questions. Maybe two-part question with regard to manufacturing. Can you provide an update as to whether this strategic refocusing has any impact on the build-out of in-house manufacturing capacity and then within the cash runway assumption, how should we think about CapEx and investment manufacturing?
RA Session II
Yeah, Kevin, thanks for the question. Obviously, manufacturing is strategically important to the company, particularly as we’re embarking on to wanting a validation run for commercial grade material. 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, so that continues to remain a strategic focus. As far as — if you could remind me of your second question?
Kevin DeGeeter
[Indiscernible] Yeah, within the cash runway guidance, how should we think about maybe cumulative CapEx or some other metrics across that time frame?
RA Session II
Yes. 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 Board gene Therapy Company and they continued with our history, understanding where the bulk of the management team came from. Controlling your own destiny remains as key strategic focus of the organization. So I think that’s where we’ll probably stop from a guidance perspective.
Kevin DeGeeter
Thank you.
Operator
Our next question is on the line of Gil Blum with Needham and Company.
Gil Blum
Hello, everyone, can you hear me?
RA Session II
Yes, we can hear you.
Gil Blum
Okay. Maybe just kind of a general question about Rett here. So because it’s a relatively larger indication, would you also expect the studies to be larger or more expensive to that account? Thank you.
RA Session II
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 costs 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.
Sure, great question Gil essentially I want to say that the studies will be thing what I will say that expense the trial programs on hold is going to be bigger. Its bigger for two reasons really first of all it is still huge [Indiscernible] everybody there. This old side a little bit more, focus on the safety matters. With regards to given very active and risk of average freshly net 82 single deliveries, multiple shipment sites.
But offline as a whole with it the stocks for the traumas you will accountability to sweeten the now have nice to see K and China than which you will very excited about ready to stop basing pacings. As a whole, going to start with an adult study, primarily safety, looking at some preliminary efficacy. Absolutely dose outs went into a pediatric pills study. While the bulk of the patients with Hexa or while we think that the [Indiscernible] prices, opportunity or increasing will be, although we think all patients with Rett will improve regardless of age.
And then, shortly after that, we will also start a pediatric boy’s study, which is somewhat unusual thing to do, given that there’s a really small number of boys around, but the boys, you’ll probably remember our stick to. So I’m very severely affected. The boss, the jump we saw in Detroit, our outlook wants to buy. So we may then maybe 200 or 300 boys in the world with it both induce some kind of rescue study there and demonstrated improvement on across low MECP2. And also worried about over expression toxicity in these boys.
It could actually quite that potential expedited part that conditions approval. So that’s how we’re approaching the Rett situation as a whole. The only thing that I would add to what Suyash just mentioned, when you start to think about Rett fully, not only do they offer a, an accelerated pathway to an approval just because of the nature of the phenotype.
The biology of the boy are quite similar to the biology of the animal model that we have for Rett, essentially, the industry standard animal model for Rett is the knockout mouse model, is essentially that model has no MECP2 and that’s, that’s basically what we’re seeing to the boy in the biology for their disease and so as Suyash mentioned, there really is less of a concern around over expression, but I think when you start to look and correlate the NINDS enabling pharmacology studies one-to-one, we’re seeing at multiple age groups a significant improvement across a number of post of the functional outcomes, respiratory outcomes, motor function, and a number of other functional assessments.
And again, when even those earlier in the real maze, we’re seeing a normalization of survival or preliminary data suggest the normalization of survival. So this gives us a lot of confidence, the opportunity, and really our goal is to not leave a patient behind here in this population. The large indication, but just associated with the girl for talking about 350,000 patients worldwide. So 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 Chico
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 best case scenario you have around 120 and what are the options there. There are a — but I guess, how would cash runway change if we had to go through extreme scenario where there was an additional study requested. Thanks very much.
RA Session II
Thanks, Laura. I’ll pick your second question first because it’s [Indiscernible]. 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 would be a pretty small study. We would essentially rollover patients that are currently in the natural history study. There is 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 need to go search for patients, so you wouldn’t have to do some type of big patient finding opportunity. But ultimately, the cash runway would be really minimally impacted. I think when you start to think 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 so strategically important because just, 1. Being able to get a [Indiscernible] at a high-quality manufacturer and the cost of 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 grade material once it’s available, and the third scenario which if you had — if we had to do another complete study. The costs are — I would say for scenario 2 to scenario 3 are pretty much the same. Because you already embarked on the production of GMP material that 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 1, 2, or 3 because you’re already doing the big cost impact, which is manufacturer of commercial grade GMP material. So that was your second question. Your first question was around the extension of cash runway. I think we’ve previously guided to cash being into the second half of 2023. We officially have been fortunate to extend cash runway by a quarter into 2025 — into Q4 of 2023.
Operator
Our next question comes from the line of Yun Zhong with BTIG. Please proceed with your question.
Yun Zhong
Hi. Good morning. Thank you very much for taking the questions. 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 a markers 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 [Indiscernible] and EGP is one of them, and just curious, would that be included in the data readout by year-end any additional markers?
Suyash Prasad
Let me make a couple of comments. The two boys in the lengthened study and adults being announced at Rett. The initial stock presented is 5E14 central VG dose. And these provisions escalate up to the 1E15 central VG. Now, I think the most important thing here, is that we have an incredibly robust pre -clinical package. It’s what allowed us to have a CTA open. And we’ve had a lot of the regulators on some of the details.
And the frequent practice behind the naval practice was designed around three studies of built-on many, many years of what the Steven Brian [Indiscernible] unit involved with. The list is both study for those [Indiscernible] perspectives of pharmacology study, which we ran in 252 mice, with [Indiscernible] well-taught mice. The 12 [Indiscernible] — sorry, 21 [Indiscernible] hawks, and we looked at a number of different doses.
A number of different age, time points of dosing mice under the whole spectrum of parameters, all of which translate nice with the clinical, some of the optimize measures, for example, looks to getting to these mice in Portland, perform active mobile visits for breathing on a whole, such of other assessments. On that particular study, we’re able to elucidate a minimally impacted dose. And then, on top of that, we also ran off toxicology studies that they will wrap and pains.
The important data was a post the end of fee base as upon distribution data. And importantly, we found with an elevated dose, all foam outsell the clinical stocking. Guys, we actually have certainly played results and toxicology with no adverse findings. And we have very high lots of DNA show good partially addition but correspondingly low levels of [Indiscernible]. The mechanistically showing that our regulations is working.
We sent the learning team for the Hong Kong study and the talks toxicology study, the Nell deliverable. This event level actually hold in regard to starting dose. And honestly its soundness, it’s why we maintained and you’ve got to when we pick thing non-device, share any appreciable toxicity, and we expect both to be efficacious. That’s how we select the base. In terms of actual measurements with, [Indiscernible] You do know, of course, that there are no official, well-known, well understood biomarkers in [Indiscernible] or in CSF.
We are looking at the [Indiscernible] biomarkers. We are looking at EEG as a potential biomarker as well and the whole [Indiscernible] the RSP, CGI, the [Indiscernible], as well as [Indiscernible] measures such as brain stem function, respiration, we’ll get seizure frequency. How many seizures gotten previously, what triggers them? So, we’ll really be guiding our dose selection on the [Indiscernible] of a safety signal and just in general progress with clinical perspective, on our side, EEG will be used in the [Indiscernible] biomarkers. We’re not hanging any decisions around the biomarkers that’s not well understood yet.
Operator
Our next question comes from the line of Silvan Tuerkcan with JMP Securities. [Indiscernible] to your question.
Silvan Tuerkcan
Good morning and 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 will be hand full and when could this start whether it makes sense to start right now or do you need to wait for your validation run in the third quarter to how much time to filing?
And then my second quick question would be on the CLN7 program. Now we’re going ahead with a first Gene construct. Do you think that’s good enough for it or you just want to get some clinical experience no matter what this program? And thank you for taking my questions.
RA Session II
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 was a small-scale engineering run, at the 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 discussion 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 definitive — 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 DLA. I still think even in the best case, it would be more of a rolling submission because they will be some still some additional work from an analytical perspective that will 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 or three, you need a 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 into three 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 [Indiscernible].
Operator
Our next question is from the line of Kristen Kluska with Cantor, please proceed with your question.
Rick Krause
Good morning. This is Rick on for Kristen. Thank you for taking our question. In terms of the prioritize programs announced today, could you please talk a little bit about the potential for grants or other non – dilutive funding opportunities around these implications. For example, we understand that federal funding bill was recently passed supporting funding for Rett syndrome research. Thank you.
RA Session II
Now, it’s a really good question. I think for Rett obviously ready GAN are squarely within the activities that we have for a ties and that’s where the bulk of our R&D investments are going. But certainly we always look for additional opportunities for non – dilutive financing, either that’s to grants, government grants, advocacy grants. We’ve done in our history, we’ve yet having spoken a lot about them. But what we’ve done in the past, it collaborate very closely with average groups where they funded a lot of the early group 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 in the IND, enabling pharmacology studies in kind of when the big dollars that you need associated with GMP [Indiscernible] before you go into a clinical trials. So these things are, are always top-of-mind and in our history, I think we’ve, we always look for ways to bring in non – dilutive forms of financing, particularly even more importance.
In a situation where the market it from a macro perspective is a little bit uncertain [Indiscernible] political 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 Rett programs that we see broad therapeutic potential, but unfortunately debts having hit our level of prioritization. Now again, we always have the opportunity to revisit that, if and when situations change.
But today, where I would say for clarity, the company has 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 non – dilutive ways along with our partner that advocacy — along with our partners at UT Southwestern for non – dilutive funding. I just wanted to answer Silvan’s second question and apologize, Silvan, for skipping over at around CLN7.
To clarify the CLN7 programs has actually gone quite well. As Suyash mentioned, we’ve recently dose the fourth patient, which is the third patient dose that one each of the 15, which is the highest dose ever given [Indiscernible] in a Gene therapy trial. Patient safety was reported at Wellness symposium earlier this year. This pace has continued 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 faster pathway to registration. So that’s really what’s 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 Yang
Thank you for taking my question. And so I have a question on GAN. So for the — toward the end of last year, you mentioned that — I think the — you’re meeting with the ex-regulatory — ex-U.S. regulatory agencies scheduled in January. So have you met with them? I know you are not going to provide an update on till later this year, but want to — just wanted to check if you have a met with them? And also in the U.S., you talked about 3 scenarios for some time. It sounds like option 2 could have been a likely option when you meet with the FDA.
Before it is option 2, what would it be the timing for [Indiscernible] filing? I think a in the past, you mentioned them around me to 2023. So want to get your updated view on that. And lastly, RA, you mentioned that your cash runway has been increased the by one quarter. So should we really think about the reduction in work force by 35% leave to one quarter extension in the cash runway? Thank you.
RA Session II
Thanks for your questions. So starting with your first question around regulatory, we have previously guided that we did conduct a meeting in late January within ex-U.S. regulatory authority around scientific advice 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 minutes.
Certainly the tone was a good meeting. It was a long meeting and 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’ve kind of coalesced around scenario two as a base case and that’s kind of the case that we are planning for internally.
What I would say is the difference between scenario two, dosing the patient 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 identifying, you’re not going out to have to identify Jason.
This would essentially be a rollover from the natural history study, as I mentioned, there is already 50 plus patients in the natural history study of which only 14 of those patients have been dosed. So you can 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 a goal with perspective, we really won’t have an issue from 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 children’s study. And then, those original phasings.
And I think it was close to about ten phasings that were dosed in that study. They didn’t allow AveXis Novartis at the time to supplement the dataset with data from the pivotal study with their commercial material that will be delivered from Libertyville, which was the commercial manufacturing facility located up in Chicago. And so this would essentially be the pathway that we’re considering as the best case because it’s the best comp that we have out there.
This is a rare pediatric life-threatening neurodegenerative disease, where there’s no therapeutic alternatives. In the case of Zolgensma, there was actually a therapeutic alternative and an approval ahead of that in Spinraza. In the case of [Indiscernible] neurolapathy, there’s nothing. And so certainly in our conversations with advocacy, and our conversations with KOL, we pressure-tested our thinking and maybe you 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 some area one, but I think realistically, I think what we’re going to do as planned for a mid — 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, into 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. It’s really how to accelerate registration option 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 dataset that we have in hand, we think there is 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 Corwin
Hey guys, thanks 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 these CLN1 or CLN7 clinical trials? Thanks.
RA Session II
Hey, Sami. Good morning. Thanks for the question. Could you repeat your first question? I’m sorry, we couldn’t hear you.
Sami Corwin
Will there be different outcome measures for patients in the Rett trial depending on their disease stage?
RA Session II
It’s a really good question. Suyash, do you want to tackle that personally?
Suyash Prasad
Yes. In general. Yes and no. [Indiscernible] We’re going to be looking at similar work buckets of [Indiscernible] measurements, regardless of [Indiscernible]. We’ll be looking at specific [Indiscernible] that RSP do, such as the meds behavior assessment, [Indiscernible] practice scale. We’ll be looking at certain seizure measurements, EEGs, for example, and [Indiscernible]. We’ll be looking for [Indiscernible] assessments that restrict the stress index, sleep apnea, etc. Communication assessments, the [Indiscernible] assessments, plus a whole host of different biomarkers, which
Operator
Thank you. Our next question is from the line of David Hoang with SMBC.
David Hoang
Hey, thanks for providing the update and taking my questions. 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, do you know 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?
RA Session II
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 Sandy’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 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.
What I’ll tell you the best tromp and that’s again would be in Zolgensma. Zolgensma, the FDA allowed us previously to use the intend as a really nice biomarker around activity in comparability between the original clinical trial material and the commercial grade material. Because the top [Indiscernible] actually pretty went up a went up pretty uniformly within the first 30 days across call pace and but you know, if you are getting really good cut target engagement.
I don’t think that’s too dissimilar here where we’re using the MFM32, which is similar in a sense size, the chop in ten for older patients. And I think when you look across the entire dataset, you do see a really nice kind of stabilization and improvement in disease as compared to the natural history quite 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, directly to what they’re going to ask for. And certainly we’re going to do what they ask us to do. But I think what well ultimately do is lean on the [Indiscernible] database that we
Operator
Please, standby. We’ll resume with your answer in a moment, Mr. Juan. Our speakers here. You may continue with your answer. It was with Mr. Juan. Please stand by, we will resume our question-and-answer session momentarily. Thank you. Please stand by everyone, our question-and-answer session will resume momentarily, thank you. Ladies and gentlemen thank you’re standing by, we will resume our question-and-answer session momentarily, please remain on the line. Thank you.
RA Session II
We’re already in session. We’re just dialing in.
Operator
We can hear you now. Please continue.
RA Session II
It’s a Gene therapy call. Operator? So we’re going to give us another go. We just dialed in, gets let us know when we dial out and we did have the bone line available and we’ll just have a bone around them. Can we go out again?
Operator
I can hear you. You can be heard into the conference again now, where we still have Mr. Hong on the line with this first question.
RA Session II
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, Zolgensma and what the FDA assets to do. As we compare to trying to use that experience for kid. So the question was really around, what would the extent of the follow-up, the extent of the follow-up, in the Zolgensma was really using the Chopping 10 as they compare at former comparator or clinical comparability of the commercial grade material.
And so we’re fortunate to have a similar assessment in that [Indiscernible], which is essentially the Chopping 10 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 competitor 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 dose, with the dose of 1.2 E^14 and and I think these patients, if they didn’t receive the intervention, we would have probably succumb. Because where this patient started was actually one of the lower scores on the MFM32. And we did essentially seeing a real nice stabilization disease now going out five years.
So I think with that totality of data, along with the pathology data from the biopsies, along that 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 suit them for the minimum amount of follow-up if possible, really just to validate that we have active drug. That could be somewhere between [Indiscernible].
Operator
Ladies and gentlemen, please stand by while we switch speakers ‘ lines. Speakers, please continue with your second line.
David Hoang
Hi, guys.
Operator
Please go ahead, you’re on your second line. I’m going to disconnect. I’m hearing feedback on the another line. May I disconnect at this time?
RA Session II
We have to disconnect the other line. Yeah. And 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 then — and again, sorry for the technical difficulties there.
Operator
Thank you. Please standby while we resume with the line of Sami Corwin. Sami, please go ahead.
Sami Corwin
Hey guys. Yeah. I think you were just going to answer my question on, if you can expect any data from CLN1 or CLN7.
RA Session II
Thanks, Sami. Yes. 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 4T, the next two that were presented was at the 1/8 to the 15 dose. And we — and we’ve mentioned that an additional patient was treated at 1A to the 15. And so we’ve already reported data on that program, and we could follow those patients. On CLN7, what we’ve decided to do is not guide to the availability of clinical data, but to say that we continue.
We’re morphing this program into — and limiting enrollment to a proof-of-concept study. A little bit different of a strategy from 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 Zhu
Thanks for taking my question and congrats on the initiation for the Rett syndrome program can have a trial. So my first — my question is on the GAN programs data because I think RA you mentioned about H-matched control. I think so far the MFM32 data you presented is mainly the overall natural history control cohort. So I was wondering what does the H-matched controls look like? Because I think you mentioned you have enough patient data there to do the specific age match.
And also it that part of the conversation or package with your [Indiscernible]. Thank you.
RA Session II
Hey 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 pre -treatment 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-matched 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 is 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 dataset that we’re going to go in and have conversations with the regulators, you’ll have natural history data, there’s 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.
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 asked Suyash. He would probably tell you that he’s never gone into a conversation with a regulator with this wealth of data before. And I think this gives us a lot of confidence around the conversation with 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 really lends itself, and it 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 [Indiscernible] for closing remarks.
RA Session II
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, is 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 and announced today has 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 organic program and it put us, again, in a position of strength. 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
Thank you, everyone who joined us today. This will conclude today’s conference call and webcast. You may now disconnect your lines this time. We thank you for your participation.
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