Taysha Gene Therapies Q4 2023 Earnings Call Transcript

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Provided by Quartr
March 19, 2024

There are 11 speakers on the call.

Operator

Greetings, and welcome to Tayshia Gene Therapies 4th Quarter and Full Year 2023 Earnings Call. At this time, all participants are in a listen only mode. A question and answer session will follow the formal presentation. As a reminder, this conference is being recorded. It is now my pleasure to introduce Haley Collins, Director, Head of Corporate Communications and Investor Relations.

Operator

Thank you. You may begin.

Speaker 1

Thank you. Good afternoon, and welcome to Tayshia's full year 2023 financial results and corporate update conference call. Earlier today, Tayshia issued a press release announcing financial results for the full year ended December 31, 2023. A copy of this press release is available on the company's website and through our SEC filings. Joining me on today's call are Sean Nolan, Tayshia's CEO Sukumar Nagandran, President and Head of R&D and Cameron Alam, Chief Financial Officer.

Speaker 1

We will hold a question and answer session following our prepared remarks. Please note that on today's call, we will be making forward looking statements, including statements relating to the therapeutic and commercial potential of TASIA-one hundred and two, including the reproducibility and durability of any favorable safety results initially seen in our first and second patients dosed in the REVEAL trial to positively impact quality of life and alter the course of disease in the patients we seek to treat, our research, development and regulatory plans for our product candidates, including timing for our clinical trials and reporting results therefrom and our current cash resources supporting our planned operating expenses and capital requirements into 2026. These statements may include the expected timing and results of clinical trials for our product candidates and other clinical and regulatory plans and the market opportunity for those programs. This call may also contain forward looking statements relating to Tayshia's growth, forecasted cash runway and future operating results, discovery and development of product candidates, strategic alliances and intellectual property as well as matters that are not historical facts or information. Various risks may cause Tayshia's actual results to differ materially from those stated or implied in such forward looking statements.

Speaker 1

These risks include uncertainties related to the timing and results of clinical trial books and regulatory actions for our product candidates, our dependence on 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 requirements of substantial funding conduct our research and development activities. For a list and description of the risks and uncertainties that we face, please see the reports we have filed with the Securities and Exchange Commission, including in our annual report on Form 10 ks for the full year ended December 31, 2023 that we filed today. This conference call contains time sensitive information that is accurate only as of the date of this live broadcast, March 19, 2024. Atascia 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 laws. With that, I would now like to turn the call over to our CEO, Sean Nolan.

Speaker 2

Thank you, Haley, and welcome everyone to our 2023 full year financial results and corporate update conference call. Today, I will begin with a brief update on our corporate and clinical activities. Then Doctor. Sukun Nagandran, President and Head of R and D of TAEJAH will provide an update on our lead TAEH-one hundred and two program and clinical evaluation for the treatment of Rett syndrome. Cameron Alam, our Chief Financial Officer will follow-up with a financial update.

Speaker 2

I will provide closing remarks and open the call up for questions. In 2023, we made tremendous progress on the development of TASIA-one hundred and two, our lead gene therapy program and clinical evaluation for the treatment of Rett syndrome, which is a rare neurodevelopmental disorder with significant unmet medical need. This included generating initial clinical data in adult patients and expanding the trial into the adolescent population, obtaining regulatory clearance to initiate the clinical evaluation of TASIA-one hundred and two in 2 additional geographies and dosing the 1st patient in our pediatric trial. Importantly, we believe these accomplishments enable us to focus our efforts this year on generating critical long term clinical data in a broad range of ages and stages of Rett syndrome patients across multiple geographies. We now have 2 ongoing first in human trials evaluating the safety and preliminary efficacy of TASIA-one hundred and two.

Speaker 2

The REVEAL Phase onetwo adolescent and adult trial in Canada and the U. S. And the REVEAL Phase onetwo pediatric trial in the United States with clearance in the U. K. Today, we are excited to report longer term clinical data from our first two adult patients treated with a low dose of TASIA-one hundred and two in our adolescent and adult trial.

Speaker 2

As a reminder, our ongoing review of Phase onetwo adolescent and adult trial is a first in human open label randomized dose escalation and dose expansion trial evaluating the safety and preliminary efficacy of TASIA-one hundred and two in females aged 12 years and older with Stage 4 Rett Syndrome. We are currently enrolling patients in Part A, the dose escalation portion of the trial, which is evaluating 2 dose levels of TASIA-one hundred and two sequentially. Two patients have been dosed to date in cohort 1 evaluating the low dose of TASIA-one hundred and two of 5.7e14 and dosing in cohort 1 is now considered complete. Today, we're pleased to provide an update on the encouraging follow-up data from the first two adult patients treated in the low dose cohort. Recall, when we initiated the REVEAL trial, there were low expectations of efficacy for the Stage 4 adult population among KOLs in the Rett syndrome community due to the advanced and relentless progression of disease.

Speaker 2

The focus was placed primarily on safety. Therefore, it was very exciting when we announced the encouraging initial impact that TASIA-one hundred and two appeared to have across multiple clinical domains in the first two adult patients treated as early as 4 weeks following the treatment that we reported in November 2023. The data presented today for patient 1 is from her 6 month post treatment assessment with clinical observations from week 35 post treatment. Importantly, we continue to see a durable response and we are seeing sustained improvement in the absence or reduction of steroid levels. We have received many questions since initiating since initially announcing Patient 1 data about the possible impact of steroids on the disease itself.

Speaker 2

We are not surprised, but nonetheless pleased to highlight today that patient improvements were maintained or further improved in the absence of steroids. As of the 6 month assessment, patient 1 has showed sustained improvement across key efficacy measures at decreased steroids at levels with new improvement observed in the Rett Syndrome Behavioral Questionnaire or RSVQ. Additionally, the second adult patient also sustained improvements across key efficacy measures with new improvement observed in certain measures including the revised motor behavior assessment or RMBA and significantly reduced seizures at 12 weeks post treatment. The longer term clinical observations reported by the principal investigator show that both patients had sustained and new improvements across multiple clinical domains including autonomic function, social communication, motor skills and seizures compared to earlier post treatment assessments. Importantly, these continued improvements were reported at week 35 following completion of the steroid taper for the first patient and at week 19 at decreased steroid levels for the second patient.

Speaker 2

As a reminder, these two patients have quite different genetic mutations. The first patient's MECP2 mutation manifests in a more severe disease phenotype than the second patient's mutation. For example, patient 1 was completely non ambulatory at baseline whereas patient 2 could walk with prompting. Despite the different clinical baseline characteristics, both patients showed improvements across multiple clinical domains as early as 4 weeks following treatment. And importantly, both patients showed sustained and new improvements across those clinical domains at the longer term assessments.

Speaker 2

In addition to the positive safety data, we are encouraged by the longer term safety profile observed. Data from the first two adult patients showed the TASIA-one hundred and two was well tolerated with no treatment emergent serious adverse events as of the 35 week assessment for patient 1 and as of the 19 week assessment for patient 2. We believe the safety profile and these continued improvements across multiple clinical domains even at reduced steroid levels in both adult patients with advanced Stage 4 Rett syndrome support the durability and transformative potential of TAYSHA-one hundred and two across multiple genotypes of Rett syndrome and further validate our construct. Suku will discuss the clinical observations and efficacy data in more detail shortly. Now let's turn to our pediatric trial.

Speaker 2

Our ongoing REVEAL Phase III pediatric trial is a 1st in human open label randomized dose escalation and dose expansion trial evaluating the safety and preliminary efficacy of TASIA-one hundred and two in females aged 5 to 8 years old with Stage 3 Rett syndrome. We are currently enrolling patients in Part A, the dose escalation portion of the trial, which is evaluating 2 dose levels of TASIA-one hundred and two sequentially. We've dosed the 1st pediatric patient in Cohort 1 evaluating the low dose of TASIA-one hundred and two of 5.7e14 here in the U. S. The Independent Data Monitoring Committee or IDMC recently convened to review these longer term clinical data from the first two adult patients and the initial 6 week data from the 1st pediatric patient treated with the low dose of TASIER 102.

Speaker 2

Following review, the IDMC approved our request to proceed to dose escalation in the adolescent and adult trial, which enables us to initiate dosing with the high dose of TASIA-one hundred and two earlier than planned. This is a critical step in our development plan as advancing to the high dose accelerates our ability to further inform our clinical development and regulatory strategy for Part B of the study by at least a quarter. With Cohort 1 now completed in our adolescent and adult trial, we plan to dose the 1st patient in cohort 2, evaluating the high dose of TASIA-one hundred and two of 1e15th in the Q2 of 2024. Initial data from Cohort 2 of the adolescent and adult trial is expected in the second half of twenty twenty four. The IDMC also approved dosing of the 2nd pediatric patient in Cohort 1 in the REVEAL Phase onetwo pediatric trial.

Speaker 2

The patient has been identified and dosing is scheduled to take place this quarter. We plan to complete enrollment in the low and high dose cohorts of the pediatric trial this year with initial available data from the low dose cohort expected in mid-twenty 24 as we disclosed previously in early January. Additionally, initial data from the high dose cohort of pediatric trials expected in the second half of twenty twenty four. Overall, we're focused on completing dosing in Part A of both studies this year. Importantly, data from Part A will be assessed by regulatory agencies and the IDMC to provide guidance to determining final key elements of Part B, the dose expansion portion of the study, including the hierarchy of efficacy endpoints, study design and the maximum tolerated dose or maximum administered dose.

Speaker 2

Another key focus in 2023 was broadening the clinical evaluation of TASIA-one hundred and two across geographies. In our REVEAL adolescent and adult trial, we recently announced the expansion of the ongoing trial in Canada into the U. S. Following our submission of the protocol to the U. S.

Speaker 2

Food and Drug Administration or FDA. We're now focused on site initiation activities in the U. S. For the adolescent and adult trial in addition to our ongoing U. S.

Speaker 2

Site initiation activities in our pediatric trial. In our REVEAL pediatric trial, we announced earlier this year that the U. K. Medicines and Healthcare Products Regulatory Agency or MHRA authorized the clinical trial application for TASIA-one hundred and two in pediatric patients with Rett syndrome, enabling expansion of our ongoing pediatric trial in the U. S.

Speaker 2

Into the U. K. And we're currently focused on site initiation activities. Additionally, we are pleased to share that TASIA-one hundred and two received innovative licensing and access 2 received innovative licensing and access pathway designation or ILAP from the MHRA, which is a program that's designed to accelerate the review path of novel treatments. We believe this further reinforces the high unmet medical need for patients with Rett syndrome.

Speaker 2

As a reminder, TAYSHA-one hundred and two has already received fast track designation and orphan drug and rare pediatric disease designations from the FDA and has been granted orphan drug designation from the European Commission for the treatment of Rett Syndrome. Lastly, we are pleased to share that we have strengthened our clinical and regulatory leadership with the promotion of Doctor. Meredith Schultz to Chief Medical Officer and Roumanah Haq Ahmed to Chief Regulatory Officer. Doctor. Schulz and Ms.

Speaker 2

Haq Ahmed will continue to report to Suku. Doctor. Schulz is a board certified licensed pediatric neurologist who is experienced in treating patients with Rett syndrome. Doctor. Schultz brings more than 17 years of clinical experience and has led numerous gene therapy clinical trials for rare diseases in her career.

Speaker 2

As Chief Medical Officer, Doctor. Schultz will lead the company's clinical development, clinical operations, medical affairs and safety activities. Ramana Hakamed brings nearly 30 years of experience in global regulatory strategy and product development in multiple therapeutic areas. She has been instrumental in the development and execution of our regulatory strategies for TAYSHA-one hundred and two including obtaining IND and CTA clearances across 3 countries and she's led the regulatory interactions across TASIA's gene therapy portfolio. She will continue to lead the company's regulatory affairs department and regulatory interactions.

Speaker 2

Doctor. Schultz and Visakh Ahmed have been instrumental to the clinical development of our TASIA-one hundred and two program and we look forward to continuing to partner with them in their new leadership positions. With a significant focus on execution in the year ahead, we believe our team is well positioned to continue to accelerate the development of TAYSHA-one hundred and two. As you can see, we have made exciting progress across our TASIA-one hundred and two program over the past year. The sustained and new improvements in both adult patients with advanced stage 4 syndrome coupled with the initial 6 week clinical data from the 1st pediatric patient that was reviewed by the IDMC support the therapeutic potential of TASIA-one hundred and two for a broad population of patients with Rett syndrome.

Speaker 2

Looking ahead, we are focused on generating clinical data across a broad range of ages and stages of patients with Rett syndrome in multiple geographies with multiple value inflection catalysts anticipated in 2024. We look forward to further evaluating the therapeutic potential of TASIA-one hundred and two for patients and families living with Rett syndrome. I will now turn the call over to Suku to provide more in-depth discussion on our clinical program in Rett syndrome. Suku?

Speaker 3

Thank you, Sean, and good afternoon, everyone. I'm pleased to provide an update on our TESHA-one hundred and two gene therapy program in clinical evaluation

Speaker 4

for the treatment of

Speaker 3

Rett syndrome. Rett syndrome is a rare neurodevelopmental disorder caused by mutations in the X linked MECP2 gene encoding methyl CpG binding protein 2 or MECP2 protein, which is essential for regulating neuronal and synaptic function in the brain. This disorder is characterized by loss of communication and hand function, slowing and regression of development, motor and respiratory impairment, seizures, intellectual disabilities and shortened life expectancy. Rett syndrome progression is divided into 4 key stages, beginning with early onset stagnation at 6 to 18 months of age, followed by rapid regression, plateau and late motor deterioration. The X chromosomal inactivation and silencing of MECP2 expression that occurs randomly with Rett syndrome results in a mixture of cells that are either deficient in or express MECP2 normally.

Speaker 3

This heterogeneity in MECP2 expression is what makes Rett syndrome challenging with traditional small molecule and simple gene therapy approaches. But we believe our construct equipped with the novel miRNA responsive autoregulatory element or miRear can appropriately address this challenge and provide therapeutic benefit. As a reminder, TAYSHA-one hundred and two is a self complementary intrathecally delivered AAV9 gene transfer therapy designed as a one time treatment. Because of the risk associated with both under and over expression of MECP2, we have combined high throughput microRNA profiling and genome mining to create miRIA, a novel miRNA target panel designed to mediate MECP expression in the central nervous system on a cell by cell basis. With mirea, endogenous microRNA which activated in the presence of MECP2 are thought to base pair with targets in the viral genome encoded mRNA and ultimately decrease protein expression levels through RNA interference.

Speaker 3

Thus TACE-one hundred and two is expected to provide the necessary function of the MECP2 protein in cells lacking MECP2 while protecting against toxic overexpression of MECP2 in healthy cells. By increasing MECP2 levels in MECP2 deficient cells and maintaining healthy levels of MECP2 output in normal cells, TASHA-one hundred and two has demonstrated the ability to produce and maintain safe transgene expression in the CNS in preclinical models. As Sean mentioned, TAYSHA-one hundred and two is currently being investigated in the ongoing REVEAL Phase III adolescent and adult trial. The trial which was designed primarily as a safety study is also measuring pre specified efficacy measures. All efficacy data being collected in this Phase 1, Phase 2 trial is hypothesis generating.

Speaker 3

As we continue to generate long term data across more patients and cohorts this year, these data across measures will further inform our thinking relative to optimal primary endpoint selection for registrational study purposes. Today, we are pleased to share the long term data from the 2 adult patients treated with TASIA-one hundred and two. I will be discussing data from 2 different time points for each patient. Efficacy assessments were captured at month 6 for patient 1 and week 12 for patient 2. Safety data and clinical observations from the principal investigator were captured at week 35 for patient 1 following completion of a steroid taper and week 19 for patient 2 at decreased steroid levels compared to earlier post treatment assessments.

Speaker 3

All these data have been reviewed by the independent data monitoring committee. We will begin with an overview of the baseline status of the 2 patients prior to treatment with TASIA-one hundred and two. As a reminder, the 2 adult patients who have been treated with the low dose of TASIA-one hundred and two differ in the severity of their disease. Both patients have been diagnosed with Stage 4 Rett syndrome, the late motor deterioration stage, which is the most advanced stage of the disease. However, the patients possess different genetic backgrounds and mutation types in the MECP2 gene, which manifest in dramatically different phenotypes and clinical severity.

Speaker 3

Studies have confirmed that MECP2 mutation types can be reliable predictor of Bedd syndrome disease severity with more severe mutations correlating to greater motor dysfunction, loss of ambulation and higher prevalence of scoliosis. Patient 1, a 20 year old female has a large deletion with her MECP2 gene that manifests as a highly severe phenotype. This patient severity is evident by her clinical presentation at baseline. Prior to treatment, she was in a constant state of hypertonia with complete loss of angulation and was wheelchair bound. She had lost the ability to sit or stand by 8 years of age as documented in the patient's medical history.

Speaker 3

She also became non verbal at this time. Additionally, the patient had limited body movement requiring constant back support and had lost fine and gross motor function early in childhood. She had very little hand function with essentially no function of a non dominant hand. She experienced frequent apnea and hyperventilation episodes and had a history of seizures. The patient's level of severity is reflected in a baseline scores across efficacy measures including clinical global impression severity or CGIS, which is a 7 point scale anchored to signs and symptoms of Rett syndrome that rate the severity of the patient's illness relative to the clinicians experience with participants who have the same diagnosis.

Speaker 3

At baseline, the patient CGS score was 6 indicating severely ill. In contrast, the second patient, a 21 year old female has a Mysis mutation in her MECP2 gene that manifests in a milder phenotype. The patient presented with a milder form of disease, which is reflected in her clinical presentation at baseline. Prior to treatment, she had only partial loss of ambulation and could walk with prompting, but she experienced progressive kyphosis and bradykinesia that developed in her late teens impacting her gait and balance as documented in the patient's medical history. Hand stereo TPs appeared at 3 years of age following regression and she mostly held her hands firmly together.

Speaker 3

She also became non verbal at this time. Her ability to reach and grasp objects was weak. Additionally, the patient experienced frequent hyperventilation episodes and had a history of frequent seizures. A level of severity in the baseline scores across efficacy measures is reflected in the baseline scores across efficacy measures. Our baseline CGIS score was 4 indicating moderately ill.

Speaker 3

The key takeaway is that there are phenotypic differences between the 2 Stage 4 patients which are correlated to their genetic status. We saw a consistent pattern of improvement across key clinical domains and efficacy measures as early as 4 weeks post treatment with the low dose of TAYSHA-one hundred and two in both adult patients despite the differences in their genetic status of severity. As Sean mentioned, we are pleased to share long term data showing that both patients are having a durable response. Specifically both patients sustained improvements and demonstrated new improvements compared to the initial post treatment assessments based on the efficacy assessments and observations from the principal investigator. Based on clinical observations from the principal investigator, both patients showed sustained and new improvements across multiple clinical domains impacting activities of daily living, including autonomic function, seizures, socialization and communication and motor skills following treatment with the low dose of TAYSHA-one hundred and two.

Speaker 3

Let's begin with an overview of the long term clinical observations for patient 1. For the protocol, prophylactic immunosuppressant therapy begin or began prior to TAYSHA-one hundred and two administration. The first patient steroid taper was initiated at week 17 and completed at week 33. A 35 week post treatment assessment, the principal investigator observed that the patient's improvements across multiple clinical domains had been maintained following completion of the steroid taper, as well as the new improvements that were observed compared to earlier post treatment assessment. Specifically 35 weeks following treatment, the first patient demonstrated sustained improvements from our initial 4 6 week assessments in multiple clinical domains after the completion of the steroid tape including motor improvements.

Speaker 3

At the patient's initial 6 week assessment, she had gained the ability to sit unassisted for the first time in over a decade and had restored movements in her legs. At week 35, following the completion of the patient's steroid taper, these improvements are sitting under assisted and restored movement in her legs had been maintained as documented by video evidence. Further, the patient sustained improvement in hand function at week 35, including the gained ability to grasp objects with a non dominant hand and transfer them to a dominant hand for the first time since infancy as documented by video evidence. At week 30 5, she also showed a sustained improvement in her ability to grasp with her dominant hand. Additionally, the patient demonstrated the ability to open a hand, dissociate a finger, scratch a nose and touch a screen following treatment.

Speaker 3

Progressive loss of hand function is a hallmark characteristic of Rett syndrome and a key concern for caregivers that impacts the patient's ability to communicate and impedes daily activities, but ultimately limits independence. These sustained improvements in hand function 35 weeks following treatment, which are not observed in the natural history of Rett syndrome are very encouraging and support the potential of TAYSHA-one hundred and two to bring meaningful therapeutic benefit to patients and caregivers. The patient also demonstrated sustained improvements in autonomic function at week 35 with improved breathing patterns, reduced breathing dysrhythmias, including less breath holding spells and infrequent hyperventilation compared to before treatment. As a result, she experienced a sustained improvement in sleep quality and duration through week 35. Caregivers reported that following treatment, the patient sleeps through the night for the first time in 20 years.

Speaker 3

Therefore, she's much more alert during the day. Additionally, poor perfusion of the extremities is a characteristic sign in patients with Rett syndrome that is thought to result from dysautonomia, meaning it's controlled by the autonomic nervous system. Therefore, it's encouraging that the patient also showed a sustained improvement in circulation at week 35 post treatment with the patient's hands and feet restored to normal temperature and color, whereas before treatment our hands and feet were usually cold and blue based on the principal investigators' clinical observations. At week 35 post treatment, the principal investigator observed new improvements in socialization and communication since the patient's initial 6 week assessment. As of the week 35 assessment, the patient was more alert and socially interactive with increased communication of her needs using vocalization.

Speaker 3

Caregivers reported that she showed an enhanced ability to use an eye driven communication device, which caregivers said she hadn't expressed interest in before treatment. Specifically following treatment, the patient was able to use the device much more efficiently with this gained ability to activate functions on the screen of the device. Difficulty in communication, including loss of speech is one of the most prominent symptoms of Rett syndrome and is an area key area of concern for caregivers as it directly interferes with the patient's ability to communicate their needs and express their interest. These new improvements observed at week 35 post treatment are highly encouraging as alternative and augmentative communication speech output technologies activated by eye gaze can be leveraged by patients and families with Rett Syndrome as a supplement to or replacement for natural speech. We believe that the ability to communicate could give patients a sense of control and greater independence.

Speaker 3

The principal investigator also observed that the patient seizures have overall been well controlled through week 35 following treatment at lower levels of anti seizure medicines relative to baseline and that the patient no longer experiences unprovoked seizures. These observations are supported by data from the seizure diaries. Now let's turn to the 2nd adult patient. At the 19 week post treatment assessment, the principal investigator observed that the patient's improvement across multiple clinical domains had been maintained while the patient was on decreased steroid levels as well as new improvements that were observed compared to initial 4 6 week assessment. Specifically, she sustained improvements in motor skills with the reduction in hand stereo tipis, which are repetitive purposeless hand movements and a diagnostic hallmark of Rett Syndrome.

Speaker 3

Before treatment, the patient mostly held her hands firmly together. Her hand stereotypies had improved for the first time since regression at age 3 at the initial 4, 6 week assessment. Based on the principal investigators observations and supported by video evidence, the patient displayed less forceful handling and the hands were more often open and relaxed through week 2019. The sustained improvement in hand stereo TPs at week 19 post treatment is encouraging and it provides new opportunities for fine motor skill learning. The patient also sustained improvements in socialization and communication through week 19 with an increased interest in social communication and activities, including increased response to spoken words and eye contact.

Speaker 3

She also sustained improvements in autonomic function at week 19 with improvements in breathing dysrhythmias including hyperventilation and reduced ethnic spells. The patient also showed sustained improvements in circulation at week 19 post treatment with the patient's hands and feet restoring normal temperature and color, whereas before treatment, the patient's hands and feet were usually cold and blue based on the principal investigator's observation. Notably, the 2nd patient demonstrated a pronounced improvement in seizure frequency at week-nineteen post treatment, the significant reduction in seizures at low levels of anti seizure medicine relative to baseline. These observations are supported by data from the seizure diaries, which I will discuss in more detail later. Both patients also demonstrated sustained and new improvements across key efficacy measures following treatment with TASHA-one hundred and two, which reinforces these clinical observations from the principal investigator.

Speaker 3

Let's begin with an update on the efficacy data reported at the 6 month post treatment assessment from the first patient. The first patient sustained improvements across key efficiency measures at decreased steroid levels and showed improvements at 6 months post treatment. Specifically, she has sustained improvement from the initial 4 week assessment in clinical global impression improvement or CGI, clinical global impression severity or CGIS, parental global impression improvement of PGII, the Rett Syndrome Hand Function Scale or RSHFS, the revised motor behavior assessment or RMBA and seizure dialysis. CGI is a clinician reported 7 point assessment of overall improvement following treatment adapted to Rett syndrome that accounts for key aspects of the disease to determine global change score. A sustained score of 2 indicating much improved was reported at the 6 month assessment, which is consistent with the score reported at the 4 week assessment.

Speaker 3

Additionally, the patient demonstrated a sustained one point improvement from the baseline score of 6 indicating severely ill to a score of 5 indicating markedly ill in CGI S at month 6, which is consistent with the score at week 4. PGII is a caregiver reported assessment of overall improvement following treatment that uses a 7 point scale, a sustained score of 2 indicating much improved was reported at month 6. The RSHFS is a clinical reported assessment of hand function in patients with Rett syndrome, which is evaluated by an experienced independent physical therapist with expertise in the hand function of Rett patients who codes a demonstrated hand function in each video at 1 of 4 levels assessing the best score for large objects ranging from no active grasping of any object to independent grasping. The highest score that can be achieved for this assessment is a 4. The first patient demonstrated a sustained improvement in RSHFS at 6 months following treatment.

Speaker 3

Although there are no changes from the baseline score of 3 indicating the ability to hold an object for at least 2 seconds in her dominant hand, she was able to increase the number of objects held from 1 to 2. Additionally, she has gained some basic grasping ability in a non dominant hand and sustained this improvement at 6 months post treatment. At baseline, she could not hold any objects in a non dominant hand and at 6 months a score of 2 was demonstrated indicating the ability to hold an object for at least 2 seconds when assisted to grasp. Again, it is very important to note that hand function improvements are rarely observed in the natural history of Rett syndrome. The RMBA, which is a 24 question clinician reported scale measuring disease behaviors of Rett syndrome, showed a total score improvement of 1 point from the baseline score of 43 to a score of 42 at month 6.

Speaker 3

Improvements are observed in motor dysfunction and respiratory behaviors. Seizure diaries showed that the patient had stable seizure events at lower level of anti seizure medication relative to baseline through week 35 post treatment based on caregiver reported medical history. Before treatment, the patient had 2 to 4 seizures per year. As of week 35, the patient's seizures are confined to periods where her anti seizure medication levels declined to below 50 micromoles per liter, whereas before treatment with TESHA-one hundred and two, she required levels of 100 micromoles per liter or greater to control her seizures. Importantly, the first patient also showed new improvement in the 6 month assessment in the Rett Syndrome behavior questionnaire, RSVQ.

Speaker 3

In RSVQ, which is a 40 5 item caregiver administered questionnaire that assesses Rett Syndrome characteristics, the patient demonstrated a 30 point total score improvement from the baseline score of 52 to a score of 22 at month 6. The score was driven by improvements in hand behavior, breathing problems, general mood, repetitive face movements, nighttime behaviors, fear and anxiety, body rocking and facial expressions. Now let us discuss the efficacy data reported at the week 12 post treatment assessment from the 2nd patient. Recall that the 2nd patient had a CGIS severity score of 4, indicating moderately ill versus a baseline CGIS score of 6, indicating severely ill for patient 1. At week 12 post treatment, the second patient demonstrated sustained and new improvements across key efficacy measures from the initial 4 week and PGII, which is consistent with the score reported at the 4 week assessment for patient 2.

Speaker 3

The patient showed a 2 point improvement in the RSBQ total score from the baseline score of 37 to a score of 35 at week 12. Improvements observed in breathing, body rocking, facial expression, general mood and repetitive face movements. Importantly, the 2nd patient also demonstrated new improvements at the 12 week assessment in RMBA. She demonstrated a 17 point improvement in the RMBA total score from the baseline score of 38 to a score of 21 at week 12, which was driven by improvements in social skills, respiratory behavior, including less frequent hyperventilation and breath holding, seizures, truncal rocking, stereotypic hand movements and our mouthing and aberrale behavior. The patient also showed new improvements at week 19 in seizures.

Speaker 3

The seizure diaries showed a significant reduction in seizure events at 25% lower levels of anti seizure medicines relative to baseline through week-nineteen post treatment based on caregiver reported medical history. Relative to the baseline seizure frequency of 2 to 4 seizures per week, there has been a significant reduction in seizures post treatment with TESHA-one hundred and two. Since treatment with TESHA-one hundred and two, patient 2 had a single seizure event with 17 weeks reported seizure free as of week-nineteen posting. There were no changes reported in CGIS or RSHFS at week 12. However, at week 12, the principal investigator reported a sustained improvement in the patient's hand stereo TPs, which are not measured in RSHFS.

Speaker 3

For the first time since regression at age 3, the patient displayed less forceful hand wringing and more open and relaxed hands. More data details on this available data can be found in our press release issued today and our Form 10 ks for the year ending in December 31, 2023 filed with the SEC. Overall, we are highly encouraged by the safety profile and the durable response reported in these long term data in both adult patients treated with the low dose of TESHA-one hundred and two. The critical takeaway is that following treatment with TESHA-one hundred and two, there were early improvements observed across multiple clinical domains in the 2 Stage IV adult patients with different genetic mutation, severity and phenotypic expression. And importantly, both patients should sustain new improvements across those clinical domains at week 35 post treatment for patient 1 and week 19 post treatment for patient 2.

Speaker 3

We believe the safety profile and continued improvements observed even at reduced steroid levels in both adult patients with advanced stage 4 Rett syndrome support the durability and transformative potential of TESHA-one hundred and two across multiple genotypes of Rett syndrome. With the low dose cohort complete in the adolescent and adult trial, we'll focus on collecting data with the high dose TESHA-one hundred and two to further explore the clinical impact of TESHA-one hundred and two in patients with Stage 4 Rett syndrome. Based on the IDMC's review of the clinical data from both adult and the initial clinical data from the 1st pediatric patient treated with a low dose of TASIA-one hundred and two, the IDMC approved our request to proceed to earlier dose escalation in the adolescent and adult trial. The IDMC also approved dosing in the 2nd pediatric patient in cohort 1, the low dose cohort in our REVEAL Phase III pediatric trial. Both REVEAL trials have 2 part trial design.

Speaker 3

Dose escalation from Part A will be assessed by the regulatory agencies and the IDMC to provide guidance on key final key elements of Part B or the dose expansion portion of the study, including hierarchy of efficacy endpoints, study duration and the maximum tolerated dose or maximum administered dose. Therefore, advancing to Cohort 2 in the adolescent and adult trial will expedite our ability to inform our clinical development and regulatory plan for Part B of the studies. This year, we are focusing on completing dosing in Part A of both trials. Anticipate significant data collection in 2024 with many clinical catalysts expected in the year ahead. As we discussed in early January, we expect to report initial safety and efficacy data from cohort 1 evaluating the low dose of TASIA-one hundred and two in the pediatric trial mid-twenty 24.

Speaker 3

We also expect to report initial data from Cohort 2 evaluating the high dose of TRATIA-one hundred and two in the second half of twenty twenty four in both the adolescent and adult and pediatric trial. As Sean noted earlier, our efforts to expand our clinical trials remain underway and we are currently focused on additional site activation in the U. S. For our adolescent and adult trial with the goal of expanding adolescent and adult trial in Canada into the U. S.

Speaker 3

We are also focused on site activation in the UK our pediatric trial with a goal of expanding our ongoing pediatric trial in the U. S. Into the UK. As a reminder, there are no approved disease modifying therapies currently available that treat the genetic root cause of Rett syndrome. There is a significant unmet medical need with Rett syndrome caused by a pathogenic likely pathogenic MHCPT mutation afflicting between 15,000 to 20,000 patients in the U.

Speaker 3

S, EU and UK and a high burden of care associated. We are pleased that TASHA-one hundred and two recently received ILAP designation from the UK MHRA. TRATIA-one hundred and two has also received Fast Track designation and Orphan Drug Designation and Rare Pediatric Designation from the FDA and has been granted orphan drug designation from the European Commission for the treatment of Rett syndrome. Overall, we're highly encouraged by the safety profile and long term efficacy reported in the first two adult patients as well as IDMC's approval to dose the 2nd pediatric patient following review of the initial 6 week clinical data from the 1st pediatric patient dosed with TAYSHA-one hundred and two. This year we are focused on collecting data across multiple ages of patients, the low and high dose of TAYSHA-one hundred and two to further inform our clinical and regulatory strategy for the next phase of the study.

Speaker 3

We look forward to sharing additional progress this year. I will now turn the call over to Cameron to discuss our financial Cameron?

Speaker 5

Thank you, Suku, and good afternoon. Revenue for the full year ended December 31, 2023 was $15,500,000 compared to $2,500,000 for the full year ended December 31, 2022, as revenue was derived entirely from our option agreement with Astellas Gene Therapies. The increase in revenue is primarily a result of Rett Syndrome research and development activities performed in 2023. Research and development expenses were $56,800,000 for the full year ended December 31, 2023 compared to $91,200,000 for the full year ended December 31, 2022. The decrease was due to reduced research and development headcount, lower research and development manufacturing expenses and a reduction in 3rd party research and development consulting fees mainly related to preclinical studies and IND enabling toxicology study.

Speaker 5

General and administrative expenses were $30,000,000 for the full year ended December 31, 2023, compared to $37,400,000 for the full year ended December 31, 2022. The decrease was primarily attributed to a reduction in compensation expenses as a result of lower headcount and reduced corporate insurance and consulting expenses. Net loss for the full year ended December 31, 2023 was $111,600,000 or $0.96 per share as compared to a net loss of $166,000,000 or $3.78 per share for the full year ended December 31, 2022. The net loss includes a non recurring and non cash expense of $34,500,000 related to the change in fair value from the pre funded warrants as a result of the August 2023 private placement financing. As of December 31, 2023, Asia had $143,900,000 in cash and cash equivalents.

Speaker 5

The company continues to expect that its current cash resources will support planned operating expenses and capital requirements into 2026. I will now turn the call back over to Sean for his closing remarks. Sean?

Speaker 2

Thank you, Cameron. As you heard today, we've made significant progress in the clinical development of our TASIA-one hundred and two program. We are highly encouraged by the safety profile and durable response reported at reduced steroid levels in the longer term data from both patients in the low dose of our REVEAL adolescent and adult trial. These continued improvements in both adult patients with advanced stage 4 Rett syndrome coupled with the IDMC's approval to dose the 2nd pediatric patient following review of the initial clinical data from the 1st pediatric patient dose with TASIA-one hundred and two reinforce the transformative potential of TASIA-one hundred and two across a broad population of patients with Rett syndrome. Building on the momentum from 2023, we believe 2024 is poised to be transformational year for the company.

Speaker 2

This year, we're focused on data generation across broad range of ages and stages of patients with Rett syndrome in multiple geographies with the goal of completing dosing in Part A of both trials with the low and high dose of TASIA-one hundred and two to inform the next phase of the studies. With many clinical catalysts expected in the year ahead, we look forward to providing additional updates on our progress. With that, I will now ask the operator to begin our Q and A session. Operator?

Operator

Thank you. Our first question comes from the line of Whitney Lejim with Canaccord. Please proceed with your question.

Speaker 1

Hey guys, thanks for all the updates.

Speaker 6

I guess to limit myself to 1, just can you help set expectations into the pediatric data mid year? And in particular, our understanding of Stage 3, and I think you guys have talked about this a little bit before, but is that the disease is kind of stable, more variable and potentially some improvements in terms of the natural history. So how should we be thinking about kind of what you could show at the initial update versus maybe over the longer term in the pediatric updates as we go through the year? Thanks.

Speaker 2

Thanks, Whitney. I guess I would say that number 1 keep in mind that the pediatric patients will likely be in a severity range of CGIS of between 46, which is similar to what's happening in adolescent and adult trial. And I think if you talk to the KOLs out there, you'd get very consistent feedback that the most appropriate severity range to study in a first in human trial for gene therapy with this particular disease. So I think, Whitney, to answer your question, you're going to see a bit of a spectrum of patients, right? Someone who's a 4 is going to be different than someone who's a 6.

Speaker 2

We've seen that with our first two adult patients here. The time to impact, it's a new population. You would like to think that you should see a relatively similar time to effect and hopefully initial magnitude of effect is relatively similar. Depending upon the severity of the disease, it's also possible that it could take longer to see change in someone that's less severe versus more severe. So if you think about a midyear readout, I would say that we dosed our first patient at the end of 2023.

Speaker 2

So we'd likely have between 4 to 6 months of data at that particular time. We've guided to dosing the second patient this quarter. So you're probably talking between 2 to 3 months of data for that patient and potentially early data for the 3rd patient depending upon the timing of that particular dosing. So hopefully that gives you a little bit of flavor of what to expect.

Speaker 6

That does. Thanks.

Speaker 3

Thank you.

Operator

Our next question comes from the line of Salveen Richter with Goldman Sachs. Please proceed with your question.

Speaker 1

Hey guys, good evening. This is Elizabeth on for Salveen. Thank you for taking our question and congrats on the data. Mechanistically, what is your hypothesis around what is driving the RFPQ improvement for patient 1 at week 25, noting that that score was relatively flat from week 4 to 12? And then how should we think about expectations for this particular score metric on the forward?

Speaker 1

Thank you.

Speaker 2

I can go first and Suku can jump in. But I would say with patient number 1, the changes that you saw in RSBQ were primarily driven by anxiety going down, general mood improving and hand function improvement. Those are the 3 main drivers in the latest decrease in that particular scale. I would just say one potential hypothesis right now on some of the mood aspects is that these patients are on very high levels of steroids for a long period of time. And we'll have to see how other patients do as well.

Speaker 2

But one potential is that reducing the steroids, the level of irritability, the impact on sleep, just the overall mood could be improving as a result of that. Put another way, it's possible that the steroids somewhat mask benefits until they're either reduced significantly or further withdrawn. So we're quite encouraged by what we've seen in that aspect of things and hopefully that gives you a bit of perspective on how we're thinking of it and we'll see it at this juncture.

Speaker 1

Got it. Thank you.

Speaker 2

Thank you.

Operator

Our next question comes from the line of Kristin Kosko with Cantor Fitzgerald. Please proceed with your question.

Speaker 1

Hi, everyone. Thanks for taking my question and congrats on these data updates. I wanted to ask about the sleep anecdote you shared for patient 1. So we understand that sleep issues are very common in Rett syndrome patients, but they can present pretty differently depending on the type of mutation. So can you speak more to the background expected for this patient based on their mutation?

Speaker 1

And essentially what difficulties they were having sleeping through the night. So was there any sleep, screaming or laughing or other notable effects And essentially what you believe is happening that you were able to see the drastic change there? Thank you.

Speaker 3

Yes. So that's an important question because as you pointed out, many patients with Rett syndrome do have significant sleep abnormalities and sometimes they also correlated with the respiratory abnormalities that can coexist. And in this patient 1, what was observed by the parents was that this patient never ever seemed to have a reasonable night sleep and always had a very disruptive night sleep, which included restless leg features, night terrors, etcetera. And post gene therapy, the feedback from the cardio, especially the father, was that this patient was now sleeping through the night and that's the first time he was getting a good night sleep. So obviously the gene therapy itself, I think, was we're speculating, but we think is restoring MECP to function in the sleep centers and probably helping with many features of sleep that resulted in this patient being restored to almost a normal state.

Speaker 3

Your second question, I think, was on seizures. So patient 1 is thought to have about 2 to 4 seizures a year. I'm sorry, did you have an

Speaker 1

Yes, sorry. Sorry, no, the question was just on the differences about sleep disturbances relative to the mutations that they experienced that they have in the Yes.

Speaker 3

So this first patient had a large deletion, which resulted in a severe phenotype. But to my knowledge, I don't think the severity of the genotype is necessarily correlated with the severity of the sleep abnormalities. That correlation doesn't seem to be clear. So but this patient anyway, patient 1 had severe sleep abnormalities. And if your question also is that what is the actual pathophysiology behind it, I don't think anybody fully understands that.

Speaker 3

But all I can tell you is the clinical observation is that the gene therapy appears to have restored normal sleep patterns. Does that help?

Speaker 1

Yes. Thank you so much. Appreciate it.

Speaker 2

Thank you.

Operator

Our next question comes from the line of Gil Blum with Needham and Company. Please proceed with your question.

Speaker 7

Good afternoon. Let me also add my congratulations to the progress. So just one from us. Can you maybe put into context the burden experienced by adult patients from being on steroids on a daily basis? And are steroids ever tapered during the standard of care for adult patients during the natural course of the disease?

Speaker 7

Thank you.

Speaker 3

Yes. So that's another good question. So immunosuppression or immunomodulation in general is not used to treat Rett patients in a disease modifying fashion. It has been tried in the past using drugs like sirolimus or prednisolone or hydrocortisone to treat Rett syndrome, but it hasn't had any positive impact on disease duration, severity or outcome. So what you are seeing in our trial though is because it's a gene therapy trial, steroids and sirolimus are being used as immunomodulatory agents to allow us to get over that initial period where there might be some theoretical risk of the treatment itself.

Operator

Our next question comes from the line of Joon Lee with Truist. Please proceed with your question.

Speaker 4

Hi, good afternoon. This is Mehdi on for Joon and congrats on the quarter and thanks for taking our questions. We have a couple, if I may. First, could you please elaborate on the safety and efficacy of using a fixed dose for patients as young as 3 years old to adults? And if you expect to achieve a comparable exposure level in the CNS of these patients?

Speaker 2

The answer to that I can start would be that the overall CNS fluid volume between a 3 year old and an adult actually is very there's very little difference, which is why we're comfortable, the IDMC is comfortable, the regulators have all been comfortable based on the preclinical data using that fixed dose in the same across patient populations essentially.

Speaker 4

Thank you. And the other question is that how do you envision a registrational trial would look like if data supports? And if you think MDRI as a measure could be considered given the nature of the disease requiring multiple domain improvement analysis?

Speaker 2

I would say a couple of things. As it relates to clinical trial design, I think the headline is we feel like there's multiple pathways that we can go down and multiple endpoints that are there for consideration, which is a good place be at this particular juncture. We've always been very steadfast in our view that we were going to use Part A to get to a better informed view and that we would have a discussion with the FDA prior to starting Part B of the study if we wanted to refine endpoints and refine our trial design. So that was one of the reasons we put our press release out a few weeks ago when we announced that the IDMC had allowed us to go to the higher dose earlier because we think that step will hopefully provide more clarity to us relative to endpoints and potentially trial design as well. So we can't say anything declarative right now about what exactly we're going to do.

Speaker 2

I would say we're we continue to be very encouraged of the pathway that we're on to be further informed in the coming quarters that can help us with the FDA. And I think in terms of the endpoints, again, we know that there's a pathway there with CGI and RSVQ and there may be additional endpoints for consideration that again we think we'll be better informed on as we continue to step through dosing patients, particularly at the high dose. Hopefully that makes sense.

Speaker 4

Thank you. Yes. Thanks for taking our questions.

Operator

Our next question comes from the line of Yanan Xu with Wells Fargo. Please proceed with your question.

Speaker 8

Great. Thank you for taking our questions. Congrats on the progress. So I was wondering, since the first patient seen a pediatric trial has gone through the 6 week safety monitoring committee evaluation. Wondering is there any color from that patient in terms of improvement that could be consistent with what you are seeing in the adult trial or in general potential for such improvement in the pediatric population?

Speaker 8

Thanks.

Speaker 2

Really appreciate the question. I just would I'd go back to we dosed the first patient, the pediatric patient at the very end of December. And about a week later, we put out a press release saying that we wanted to begin to disclose data on a cohort basis and that we felt that was the most appropriate thing to do versus going patient by patient. And so all I can tell you at this point in time is that the IDMC saw the initial pediatric data as well as the data that we just reported on the 2 adults. And that was in their calculus as they decided that we could go to the high dose in the adolescent and adult study and we could proceed to dosing the 2nd adolescent patient.

Speaker 2

So beyond that, we'd really prefer not to comment and proceed with our path forward to disclosing that data in a more fulsome manner at midyear.

Speaker 8

Understood. Thank you for the answer. If I may do a quick follow-up question on the patient 1, patient 2 in the adult data set. We can see clearly patient 1 has continued improvement or new improvement in RSP2, patient 2 has new improvement in RMDA. But interestingly, the other endpoint for those patients seems to be pretty flat.

Speaker 8

So how do you think about that? And is there a potential for the other endpoint to also improve in the future? Thank you.

Speaker 2

If you're referring to like CGI, I would say that Is that what you're talking about?

Speaker 8

Sorry, sorry. CGI, I fully appreciate that. Even maintenance of the prior numbers according to our check with the doctors that's a very, very incurring sign to have those minimally improved ratings maintained in a following in a follow-up and also to have the much improved for the other patient maintain. Those are great achievements. I'm talking about RSBQ and RMBA, where both patients had one score improved and the other score relatively flat.

Speaker 8

Yes, so that's what I'm talking.

Speaker 2

I got you. So in patient number 1, so first of all, the RMDA is administered by the clinician in the hospital. The RSPQ is provided by the caregivers in the home setting and they ask different questions, okay. So it's a little difficult to put apples to oranges. But I would say this, we actually asked the primary investigator the same question.

Speaker 2

And what she said was the patient number 1 has gotten very aware of what's going on in her surroundings. If I showed you the video from pre treatment, she was very, very almost like in a catatonic state in a wheelchair, really not interacting. Now she's much more aware. She's trying to communicate and vocalize. And basically what the PI told us is she does not like going through the testing at the hospital.

Speaker 2

She gets irritated and she doesn't want to cooperate. And at this point, she has the strength to not cooperate. So that has been driving some of the it's driving the score that you're saying. She's essentially not necessarily cooperating with some aspects of the disease of the testing, where in the home setting, she's getting very much a comfortable situation and she's the parents are seeing it. The other thing I would say is that some of the improvement that I mentioned earlier in the RSPQ that patient 1 had was in the anxiety, the general mood aspect of things that is not captured in the RMBA.

Speaker 2

So that's one aspect there. On patient 2, her RMBA improved significantly and it was driven essentially by her socialization, her interest in communicating with people and also her seizures. Those were big drivers. In the RSBQ, neither of those is addressed, neither one of those is quantified. And in the RSPQ, again, she had an elevation in anxiety and some of the NITON behaviors, which again, if you think about what I said about patient 1 on steroids, that could also be the case.

Speaker 2

She has had a bit of an issue with tolerating the steroids. So hopefully again that gives you some perspective on those two things and Suku had something to add as well.

Speaker 3

Yes. And also for patient too, I would highlight the seizures were decreased by 95% post gene therapy treatment. So this patient had, I think, 8 to 16 seizures a month. And other than one seizure, day 13 post treatment, the patient has had none, no new seizures. And also the use of a combination anti epileptic meds have dropped by 25%.

Speaker 3

That is a big deal from a clinical standpoint and for the parents and caregivers and from an activities of daily living standpoint. The second thing you should notice in patient 2, some of the hand function and stereotypic movements have decreased, which also makes it promising that this patient may eventually get independent functionality of the hands. And there is something else that goes on in about 40% of these patients with Rett syndrome, which is the upper and lower extremities have abnormal circulation, which means the hands and feet get quite cold and at times painful. And you would note in patient 2 and patient 1, that resolved post gene therapy treatment. So other than RMB and RSVQ, which obviously we focus on for different reasons, these major clinical observations, I think could be life changing in this patient population.

Operator

Our next question comes from the line of Jack Allen, Robert W. Baird. Please proceed with your question.

Speaker 9

All right. Thanks for taking the question and congratulations on the progress. I'm looking to zoom out a little bit and take attention to the Astellas collaboration that you have. It seems like you're really developing data quite quickly, especially with the pediatric low dose data expected in the middle of this year and the potential initial high dose data later this year. Can you remind us of the structure of the STELOS deal and how it relates to the rep program and what measures are in place to ensure you get a fair deal?

Speaker 9

I believe the option was fairly open ended when that deal was struck.

Speaker 2

Yes. I mean essentially what Astellas has is a right to negotiate an option with us, an exclusive right that they have. There's no predetermined terms to your particular point. The option period gets triggered after a number of about a handful of pediatric patients have call it 6 months of data or so. So there's no time crunch at this particular point in time where Astellas has to come in and either request an opt in or not.

Speaker 2

That's likely a 2025 topic. The other point that I want to really stress is that Astellas certainly has line of sight to things, but it doesn't the agreement itself doesn't preclude another party who might be interested in the program or in the company from making an unsolicited offer. That's fine. We would just have to notify Astellas of that and they would have the ability to counter if you will. But there's no blocking right in it.

Speaker 2

Hopefully, Jack, that gives you some perspective on that or did you have a follow-up? Yes. That's great color. I actually

Speaker 9

do have a brief follow-up around enrollment. How are you thinking about enrollment in these studies and any inter patient staggers? I know your competitor has recently announced that they're expanding a lower dose cohort and they're allowed to dose in concurrence. At what point do you think you could get to concurrent dosing and what's the current stagger between patients right now?

Speaker 2

The current stagger is 42 days and an IDMC meeting before you can proceed to the next patient. I think that it's a bit of an art and a science. And I think it's when you have enough data that you can make a request to remove the stagger. I think for us a good point is we preliminary efficacy and based on the preclinical data there's a rationale to go to a higher dose and we're able to do that. So instead of dosing 3 low dose patients in the adult study, we were able to do 2 patients and then move to the higher dose, which we think is going to be more informative to the overall program and potentially better for patients.

Speaker 2

So if you apply that logic, there would be a point in time where we would be comfortable potentially going to the IDMC and talking about removing the stagger. And that's just something we'll have to do when we feel that we've got data that we feel sufficient to support that request in a credible manner.

Speaker 9

Got it. Great. Thanks so much for the color and congratulations again on the progress.

Speaker 2

Thanks, Jay.

Operator

We have time for one last question. Our last question comes from the line of Sylvain Tuckin with Citizens JMP. Please proceed with your question.

Speaker 10

Yes, thank you. Congrats on the great update and thank you for taking my question. I just have a question about your dose. Roughly going ahead, you can double the dose faster than you expected. Can you just talk about what that means in terms of the efficacy results that you're hoping for?

Speaker 10

Did you think there could be a greater increase? Or what is your hope for the higher dose here?

Speaker 2

I'll start and ask sucuduapine as well. But first of all, when you look at the preclinical data, there is a dose response. So you would expect there to be a greater response moving to the higher dose. What's driving that? You'd anticipate that by giving roughly at 75%, 80% more dose that you'd be transducing more cells, you'd be generating more MECP2 in the cells that need more MECP2 and that overall you should have a more significant clinical effect than what we've seen in the low dose.

Speaker 10

Thank you. Yes, if I may have a quick

Operator

That is all the time

Speaker 3

we have for questions.

Operator

I'd like to hand it back to management for closing remarks.

Speaker 2

Okay. I just want to thank everyone for taking the time and appreciate you listening to the story and we're eager to continue to progress in 2024 and generate additional data and hopefully more value creating milestones for the investors and care for the patients. So thank you and have a good night.

Operator

Ladies and gentlemen, this does conclude today's teleconference.

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Earnings Conference Call
Taysha Gene Therapies Q4 2023
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