TSHA - Earnings call transcript Q1 2024 | Taysha Gene Therapies, Inc.

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Operator

Greetings, and welcome to the Taysha Gene Therapies First Quarter 2024 Earnings Call. [Operator Instructions] As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Hayleigh Collins. Thank you.

You may begin.

Hayleigh Collins

you. Thank welcome Conference Quarter Call. and and Financial Taysha's Update Corporate to afternoon, XXXX First Results Good XX, Earlier announcing the March financial Taysha results today, issued for first a quarter press release XXXX. ended release is copy and our filings. SEC this A available through of the company's on website press

today's Sean Joining and CEO; President Nolan, Sukumar Officer. me on of Chief R&D; Financial Taysha's Nagendran, Head and call are Kamran Alam,

statements [ question-and-answer note and cash will our the force to clinical a our for expenses and any hold of life session statements of forward-looking that be patient trials ] in capital seen we today's will prepared disease product potential Please timeline results reporting first following the favorable the We remarks. regulatory reproducibility quality in our to impact and dosed our candidates, results we positively into on call, making treat current commercial plans in trial of planned XXXX. therapeutic seek our second including requirements operating resources and development relating the our in supporting patients research, initially and our and for and the durability of including TSHA-XXX, including to therefrom, REVEAL

results from or risks such may statements. well growth, call candidates, or clinical This include may timing may for Various and also historical cash matters plans, Taysha's the not alliances other forward-looking in future and actual These that forecasted facts statements discovery clinical operating and intellectual regulatory of results, runway as programs. our and contain trials implied to relating property results those expected as development strategic product of for and and forward-looking and materially opportunity product Taysha's to candidates the those information. stated differ cause statements market are

protection and for third-party include the to product strategic our requirements ponder of research regulatory by [indiscernible] our and ability and funding related clinical imposed activities. limitations development our other alliances of our timing relationships; to discoveries, substantial dependence for candidates, and by and the These patent interactions controlled trials our parties risks uncertainties upon conduct third and

description the we filed face, the in Commission, quarterly on Form have the that list filed Securities please our risks the of and Exchange today. and the ended Form quarter XX, with a we our we that annual full on including XXXX, For XX, and XXXX, for reports XX-K and ended year that report XX-Q for report see March December uncertainties

date May that or to the call, Sean to conference of circumstances except be time-sensitive contains CEO, XX, the securities this required live only conference that, update no to call forward-looking of obligation With This over call XXXX. broadcast, events information Taysha as of or as our reflect undertakes by I statements date this is turn applicable accurate to the after would may Nolan. revise like now laws.

Sean Nolan

evaluation with up of program call will and Officer, Thank recent Today, will Suku a remarks Head R&D update financial will Hayleigh, first provide provide on financial our I Chief the clinical TSHA-XXX open closing an our questions. for for Alam, Financial up of lead update Kamran syndrome. follow treatment Rett update. in of and welcome quarter the will everyone brief I quarter activities. you, begin a on to Nagendran, President Conference Call. results XXXX our Dr. with Update Then Taysha, and and our

data encouraging lead we in TSHA-XXX, This recent X low-dose to made therapy We Rett treatment the our first dosed gene reporting evaluation clinical the longer-term advance with are adult cohort. includes the of progress that pleased for patients the syndrome. program for in

planned, trial regenerative in Phase pediatric our I/II Phase cohort the high-dose and adolescent and first the than receiving earlier I/II REVEAL trial enrolling of patient And the dosing REVEAL adult patient second in medicine our advanced I of TSHA-XXX. Rett believe gene clinical for across evaluation from therapeutic designation and continued therapy patients a syndrome of reinforces this with the of FDA the our broad supports progress therapy TSHA-XXX program. population potential the

upcoming We with for of we value-creating critical for next the milestones our key believe patients stages execution that are across of multiple Rett continued longer-term syndrome range goal phase guide our with that ages across TSHA-XXX program, our generating well broad clinical geographies positioned data of and the in studies. of will

care need of syndrome and Rett unmet burden high. is The for

and has therapy protein makes traditional our or approaches. regulatory candidate miRNA responsive the with with treat and to MI cell-by-cell overcome spread on mosaic small therapy estimated by disease-modifying pattern disease, MECPX XX,XXX mixture under to and the express causes medical rare the technology nervous therapies and protein neurodevelopmental syndrome of protein. States, challenging mutations gene, results patients inactivation Currently, either element the are MECPX MECPX rare in the in MECPX gene [indiscernible] affects potential address this We syndrome believe expression unmet normally, Kingdom. a need. a of approved disorder significant basis which that the system to are equipped the or United of associated Rett United caused The the European challenge to As MECPX Union gene risks novel that the Rett XX,XXX random an mediating see MECPX central over in TSHA-XXX by cells of appropriately molecule there is deficient both a expression with subsequent genetic in and a there

are trial Phase place trial in U.S. pediatric evaluating the in Canada We [ the a U.S. an in I/II X the and REVEAL taking adolescent in with place taking and adult TSHA-XXX and on clearance trials, U.K. ]

first and adult efficacy aged XX safety in TSHA-XXX Rett females trial I/II the of Phase preliminary with years As and older syndrome. human reminder, a REVEAL is a in our assessing study ilescent

the enrolling dose escalation evaluating of Part is portion We A, dose are patients the which sequentially. currently TSHA-XXX of trial, in levels X

the complete. been considered and date XX have of dosing of X to is vector dose Two total cohort in [indiscernible] with dosed TSHA-XXX cohort X.X patients X low not genomes in

independent treated IDMC, assessed or request TSHA-XXX dose will escalation approved guidance elements patients be early with aspect regulatory B pediatric trial to [indiscernible] Part the the from from across of the our data trial. the data trial, adult of the key monitoring trial adult and our provide to and clinical by the an adolescent to trial. of review adolescent Following proceed in the A and final determine of to the agencies Data IDMC Part and

[indiscernible] view We're The dose our portion, genome has advancing high a dose sedationand take is X share dose total patient expansion including quarter [indiscernible] TSHA-XXX ] dose. XXXX. in of in the study on and efficacy Cohort administered to first B. and evaluating enrolled the than of dosing of the tolerated to planned strategy Therefore, Part here maximum for [ vector in the endpoints, hierarchy maximum former dose the pleased cohort or X place accelerates XX scheduled of clinical development been regulatory second high to

last duration in this following patients community, the treatment, X having November with to disease. TSHA-XXX leaders Earlier we year, disease. encouraging on patients opinion syndrome low-dose key genetic reveal, late genetic when participants have a severity. X who primarily in focus X for X we adult expectation first of and of across efficacy are announced motor little exciting safety was our the it stage clinical advanced very appeared very population of among and initiated treated was Therefore, in Recall, the the as impact the encouraging data early weeks the despite the multiple adult severity mutations different to adult as cohort initial domains to disease Rett longer-term trial Rett for announce Stage of different the and the first syndrome mutations with

follow-up We for presented of in quarter patients assessment follow-up X-month of showing the first a the first adult longer-term a response in sustained durable new year, improvements steroid data including with [indiscernible] deduction levels. the the this

X X-month steroid new levels Behavioral RSBQ. in measures key improved showed or with the sustained Rett the of efficacy at assessment, Questionnaire, patient improvements Syndrome observed As decreased

across improvements Additionally, of and as certain observed patients treatment. assessment the new XX-week revised for assessment including as measures XX-week MDA following with improvements adult reduce of measures, in second the the [indiscernible] significantly key efficacy seizures demonstrated assessment Motor the our sustained

both socialization and had compared earlier observations principal new activities daily communication, Moreover, the across motor function the showed post-treatment and impacting clinical sustained improvements seizures multiple that of patients to including living, by clinical assessments. skills, domains autonomic longer-term indicator reported

as of improvements observations week for adult at at adult multiple second following X at the a patients Suku Patient and assessment We clinical X. continued in those reduced the adult will patient. is XX, even levels, patient detail. and events these The potential in in TSHA-XXX construct. steroids more XX with of XX both patients completion for believe across week steroid at Importantly, showed validates syndrome treated domains, durability also well and tolerated XX-week taper as Rett Patient patients both first profile was multiple and safety our from for the assessment the IV these discuss reported longer-term supports treatment encouraging. week first syndrome [indiscernible] for were Stage decreased emergent the the continued with profile genotypes the TSHA-XXX steroid and TSHA-XXX, -- with safety Rett transformational no that further Data X advanced improvement levels of of across

where of are the the patients of We pediatric different the response consistent and treated profile in the to TSHA-XXX see therapeutic dose TSHA-XXX. with on across in we pediatric potential a evaluating similar clinical population, a with domains focused genotypes also pattern low of hope

preliminary Phase aged efficacy REVEAL syndrome, TSHA-XXX trial is ongoing pediatric to and of in evaluating female years Rett X the safety X Our old. patient I/II

which pediatric We Sequentially. of levels Part of are trial, currently will A in the TSHA-XXX. [indiscernible] patients enrolling evaluate

of X-week patient data the dosed in have patient low-dose the cohort We second review first initial the X, from the cohort dose. following the IDMC pediatric pediatric

understand disease many is While present earlier X trial, the a symptoms of population Rett most to have already an developed disease important of adult and the with patients therefore, our disease younger with and syndrome patient this compared captures adolescent manifestations. trial Stage hallmark to it stage advanced with that

hand gate spoken movements, also rapid the approach and typically that symptom characterized independence age a in to in and by relating skills stage leads most dependence. disease stereotypic Many patients quality of this from can seizures to results regression is impact cases, group of deterioration language, period of Studostationary in life. as suffer purpose, known which lifelong partial their hand significantly the purposeful also of The and loss period and and after learn hand regression III or acquired abnormalities particularly caregiver of language skills, loss Stage movement. complete Patients

population, across will backgrounds, is heterogeneity broad help patients data to in to in key the result hope development a us set domains Rett pediatric to goal We the bring backgrounds to which bringing our a in inform is intended include of treated low-dose pattern us high in pediatric Similar symptoms for the severity and genetic closer phenotypic to spectrum response trial genetic the study. of clinical genotypes plan that potentially variable all robust different A to of which to the the transformative among syndrome. will a across spectrum of pediatric treatment next Rett broad of with a due with our see believe patients patients the Part generate consistent adult the patients cohort, syndrome. of we phase

is Recently, the pleased medicines FDA, were efficacy first low or unmet therapy of reverse a following review a patients Advanced data such and indicates adult designation from regenerative potential receive designation if the to the of address Regenerative we to patient for dose X condition needs and it TSHA-XXX. RMAT first treat, Therapy pediatric RMAT modify, with evidence has medicine from safety and to the condition. dose serious available intended the the is clinical therapy for preliminary cure or eligible

meaningful companies patients recognition designation expedite senior the syndrome help RMAT unmet to is development. FDA therapeutic benefit involving reinforces We drug need receiving can Rett important in the from to from and to Rett interactions of TSHA-XXX and with bring and with receiving designation the families RMAT syndrome. that FDA managers Sponsored potential an increased believe high change

focused year advance closely pediatric continue We longer-term expanding as agencies will on with remain our into forward of the age to Rett program. across groups we and population work we phase patients as ahead multiple broad clinical trials look the further patients, TSHA-XXX other regulatory FDA generating to We of studies. the our guide the a next with critical that geographies, in and will evaluating dose data executing syndrome across high

cohort and trial an mid-XXXX. from clinical low-dose REVEAL, the completed our initial expect to pediatric data and low-dose We our REVEAL the trial of data provide cohort update adolescent on available adult in from of

data trials from for available REVEAL Additionally, we in expect report to initial second high-dose both cohort the the of half XXXX. our of

call I to will to provide now of Suku? in-depth TSHA-XXX. turn the a over Suku more discussion

Sukumar Nagendran

gene TSHA-XXX disorder caused the I'm [indiscernible], essential pleased good you, synaptic the and on program for therapy the The syndrome. update Thank an disorder Rett an is which disabilities onset XX brain. and hand of afternoon, function, the rare is function characterized syndrome of the to communication syndrome aggression neurodevelopmental everyone. shortened neuronal by X regulator mutations intellectual expectancy. and to provide regression impairment, a treatment lots in Sean, of our MECPX protein, in evaluation and slowing of divided seizures, rapid [indiscernible] clinical by beginning Rett followed Rett encodes motor in much progression key is and into early deterioration. by X months development, and at with late and/or of respiratory age, pathing stagnation stages life

expression have Clinical MECPX miRNA the and high-throughput miRNA a therapy estimated controls associated a in over to support AAVX self-complementary with delivered of ultimately As a system of risks expression healthy treatment. of TSHA-XXX combined is encoded against and protein MECPX, in produce and function the micro MECPX. With in an expression RNA we basis, designed to to provide RNA to is MECPX the gene MECPX expression reminder, transfer Thus, toxic the a cells. central cells levels under create RNA of TSHA-XXX protein Emira micro levels Because our therapeutic decrease expected [indiscernible] while -- intrathecally through levels the thought to gene panel maintain both in data profiling central as the of interference. rarenrgenous MECPX protein onetime in safe MI expression designed to products lacking [indiscernible] cell-by-cell necessary the nerve the to in mediate continue MECPX expression target itself. the on and of presence nerve protecting ability of TSHA-XXX are pre-clinical

we our These and the pattern mutations adolescent of of a in treated I/II adult without of REVEAL have response cohort trial. mentioned, stability. in disease domains, both and Sean daily observed activities As very associated multiple across living similar clinical patients low-dose genetic patients Phase different impacting

phenotype female The with MECPX first our XX-year-old disease manifests a that was nonambulatory deletion completely and patient in [ a large with is baseline. severe ] at most

second Mysense and XX-year-old milder as gene manifest with While female, the mutation at her walk is a a a MECPX could that it's phenotype in something patient baseline.

the principal immunosuppression therapy the to [indiscernible] to had [indiscernible] XX patient across earlier and maintained prophylactic observed XX post-treatment prior TSHA-XXX improvement that initial the paper protocol, The been domains Further and treatment assessments. paper multiple began completed XX new at administration. clinical assessment, initiated week ] steriod by [ compared improvements investigator week of weeks following X observed completion [indiscernible] Basically, following treatment. for

a infancy. and patient The in first first to to hand in the for and gained sit a to since time like ability function, objects transfer decade motor sustained and movement the including for showed hand time ability unassisted improvement dominant his grasp hands over function, the with nondominant restored a first the including them

its concern function, potential key natural Progressive are communication, We hand the meaningful Rett support of hand loss and which and to believe [indiscernible] [indiscernible], for observed in to the bring Rett limits, typically change of of of characteristic a is The the syndrome. activities of improvements independence. syndrome in sustained caregivers. function not patients hallmark patients history area therapeutic daily

the increased investigator an alert communication, the XX enhanced in communication device. localization more day. ability new and being improvement in were observed to A sleep Sustained and the first they and as patient first XX to the in years, the use night week sleep gain socialization for the function first in improved ID treatment, the the patient breathing and through autonomic pattern, in post during including patient, interactive observed quality resulting improvements ability circulation in also time principal including

to Difficulty control prominent a for a their communicate caregiver loss express the in also of independence. give communicate and symptom syndrome patient's is with communication of we greater as interfere a key believe area Rett Based of of on to interest. speech ability patients the their directly concern needs input, sense in caregivers to and and it ability

control longer to seizures. no directive now week levels for and medication, seizure seizures several unprovoke baseline well patients experience a at overall antiseizure patient with lower event the First XX of

Now to patient, adult let's the turn patient. second second,

was words At a level patient improvements principal the a significant the also enhanced sustained time at and assessment, since scale patient patient and the relative with the patents week building including lower with eye motor The and in movement social, [indiscernible] in improvement saw reduction The XX% spoken XX first circulation. in serial post-treatment decreased and and medicine communication communication [indiscernible] function improvements in [indiscernible] on age socialization to of contact. X increased response activities, to XX-week increased baseline. while and second regressing sustained new observed improvements levels, in to showed investigator interest seizures with also patient at with anti-seizure in and

decreased X seizure approximately and patient question seizures. to for assessment The RSBQ demonstrated post-treatment X-month efficacy of implement And the key X improvement global assessment and second on urban assessment has [indiscernible] Atonally, behavior clinical week. measures PGII, page. free the cases patient This patient's ] for CGII, across patients syndrome and reported based first or seizures pretreatment per assessment. weeks seizure revised RMBA, improvement sustained consistent our [indiscernible] the been in continued Rett both caregiver in the and XX-week of on improvement includes motor impression and behavior level XXth impression of [ for the clinical XX

developing encouraged earlier by a at similar observations at treatment both their measures of severity. and a improvements, investigators. the are X-month improvement believe with key to syndrome adult were principal entirely early from follow-up potential demonstrated these even for we These long-term sustained also with profile efficacy patients different Rett safety syndrome. the Rett well-tolerated across steroid the genotypes levels, reduced the patients CGIF supports adult scale, clinical assessments function We responses patient in treatment the TSHA-XXX transformative multiple post new X that but durability completed and first The through a assessment. improvements Overall, and the relative sustained for reinforces and hand consistent across disease assessments

the TSHA-XXX. to the impact With the the in scheduled is adult to and the enrolled second adolescent data quarter are focused low XXXX. in cohort the the further currently dose the first high-dose with dose complete patient of cohort collecting clinical dosing explore place high we of on and take We trial,

trial. I/II was measures pediatric is and primarily trial Part adult the across our collected a first to clinical Phase a patients Part A the data Phase evaluate the is patients. with REVEAL broad will safety being to generating inform to designed relative across adolescent of turn let's Its trial and study. thinking impact I/II include REVEAL title similar Now of as TSHA-XXX variety pediatric of intended hypothesis trial. the range We to diversity backgrounds. B Therefore, of pediatric the Efficacy

the pediatric in attributed mentioned, the is results protein chromosome occurs individuals Sean mutation to with [indiscernible] similar the a miniature expression. patients broad random inactivation variation adult difference MECPX therapeutic due amongst that with same As cells background spectrum genotypic heterogeneity ex is the population, between result to in commonly that syndrome, patients levels with high organic different in MECPX and mixture the different of and to Rett of symptoms

severity of stage the the baseline data, regardless to this, disease. patients and overall the of be of of Because age importance of to interpreting of the continue when consider setters will disease

dose the TSHA-XXX patients patients. of meaningful show Our hope profile across observed we pediatric and the with clinical in will different with that consistent have treated recapitalize genotypes, that the safety low adult improvement the is domains were

to focused available data lower in patients X the anticipate first the and from X the a -- the completing data report part initial first we both dosed and mid-XXXX. XXXX. trials Cohort have efficacy have remain of pediatric safe X We dosing We on discussed in of cohort TSHA-XXX, significant revere dose in expect evaluating X collection pediatric

on goal efforts activation trials REVEAL, we're in focus focused adolescent trial of in site U.S. ongoing in the our our U.K. expanding the underway remain the of for the into as clinical our on activation the trial Our Canada to trial have expand pediatric well. hard and the goal U.K. pediatric into trial our in U.S. ongoing the we and with site expanding adult additional the In as REVEAL with U.S.

turn our I call the Kamran? Kamran now will to financial results. to discuss over

Kamran Alam

to by development increase were and primarily ended was driven practice, March representative GMP the batch activities The XXXX. Thank the ending million you, March is TSHA-XXX. or Suku. months increase an months intended XXXX, and March XXXX, for months XX, XX, X million Research during of million $XX.X $X.X X commercial $XX.X manufacturing for good for the process expenses X XX, manufacturing compared which ended in the

March adult X and clinical million XXXX, primarily the activities expenses XXXX. and increased XX, Additionally, for trial expenses the XX, X REVEAL, $X.X trials. compared and General million pediatric the administrative March ended to months ongoing adolescent, months due were to for $X.X ended

as $X.X The professional administrative and consulting million decrease was to as compared ended a XXXX, or reduction per the in or share for for the and headcount fees. was X result March XX, Net XXXX. net a compensation loss of million due XX, loss months of months million per general $XX.X and X reduced share of lower March ended a $X.XX to $X.XX $XX.X

that will March into The support its plant As and requirements had operating cash Taysha current expect million company $XXX and continues capital cash resources to XXXX, XXXX. of equivalents. cash in XX, expenses

over the I for will now Sean back call his Sean? remarks. turn closing to

Sean Nolan

encouraging, XXX to are and very the a moving across and population with forward Rett ages of patients of the Thank both patient new Stage broad with syndrome. first stages of syndrome to Rett and of you, improvements development sustain evaluating have clinical X patients we to important the the made XXXX, adult TSHA-XXX Kamran. Throughout quarter on progress look further high dose in advanced we

escalation inform phase the focused to of both collecting REVEAL of dose are completing our and studies. on our next trials for We data

to and reporting low-dose pediatric from many adult adolescent mid-XXXX. updates patient clinical the providing including initial expected, clinical look we data improvement and update trial adult REVEAL adolescent and to patterns forward REVEAL, populations. additional cohort in our completed of on for similar pediatric an In from our trial look ahead, the continue milestones we will and providing We have across year

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

Operator

Instructions] [Operator

The first is have Kriten we Kluska question Cantor Fitzgerald. of from

Kristen Kluska

Congrats on the designation. RMAT

So a very we younger the Street, questions lot but the to data you of collected in providing patients all transparent about trial. continue to the for you've been the -- get expectations

ways we different stand should isn't thinking be how this heterogeneic domains there for about patients, to some that are but as since I measure So anecdotes population advanced? in genetic backgrounds, with particular out? know younger far any

Sean Nolan

for Suku [ have But ] the have have or not Kristen. what's very Thanks disease. long. important And may that X very or think are people had it for X something symptoms to I'll had that hallmark further all lines. adults patient X question, studying again, But those take it they have has advanced time XX again, along it. who may that we generally they to the the a stab the I they is, ask we're that years all fact ages at that and on recognize population pediatric

and very entrenched the the be a the on severities it's to So disease, genotypes. different based

with post think we're would And belief I So adults. our pediatric ultimately time, a occurring reason have systematic with let's that the further time perspective, that that that But be therapy I think I occurring better could I to course mean improvements. dealing here. outcome of across potentially remember, it say, and the And you they it's dramatic if patients, just clinical very over would what make in transformational it takes from it first people stands there's treatment. domains the in than, if be that for terms most X it rapidly of reinforce probably appreciate to may the have call our low post that response to it a in would XX coming at we're response adults, be think, multiple birth. months meaning you dose children, dramatic a to be, impact what seeing to the can -- the XX the on put in words consistent

time there. takes it develop get mentally to So and

the transformational been consistently is in speak gross don't for to see and you tell happening are the in improving, things I I able us fine be disease to that reasonable. function first But perspective to that do, years, again, keeping if are if the becoming if X going mind that a improves, we've the from haven't think as is clinical there's And improvement, seizure what you those can motor and are happening is the effect example, months, think a at efficient communication had more and an so I they you improving, socialization that low got dose. expect to the function hands motor think in attended going multiple the occurrence we're

Suku there you to pause is Let perspective me and anything ask for there would add Kristen? for that

Sukumar Nagendran

think cause what or so replacement So The far patients disease, of of consistent adult that shown Kristen think, of a duration mean, presentation these the disease, I just, remind laid also the with presentation the the it we've that root therapy. And at severity the I our it's clinical have. patients. audience this is you, out patients, Sean, whether gene drive I and would the very mean, times is and the that of syndromic the efficacy complex the clearly. will also I I that given older we treating the severity genotype patients younger in actual That are

So what the the to age have patients therapy, to the as I'm see this saying I I that gather trial treat we well. the is, data confirm think will but we as this fairly in efficaciously, patients think, pediatric ranges and gene across recruit

Kristen Kluska

to patient you the my And or had follow-up, you I data -- you that that for length appreciate the share any can gave RMAT designation? But the they FDA can't us the amount when very designation, was then from That the patients for helpful. third data of comment yet. from patient this

Sean Nolan

Thank could question? you take you, you to Yes. that want Suku, do -- Kristen.

Sukumar Nagendran

Absolutely, sure. Yes, Sean.

consider we we receive that as with and the RMAT who has So reviewed FDA. with they qualify know, designation. the to -- there set a the in needs time patients that you to data Canada commits the and the filed when are medical justifies the disease FDA our you found impact sponsor clinical in and and designation, will product FDA pediatric adult that obviously X the working this now program a its we And between the once significant to to U.S. X product has filed significant And more sponsor because the collaboration is get dose on in system, RMAT data designation the for the from patient, was dosed the and close then unmet trying RMAT very then address, lot commitment what

it's we good very and So received for that overall, we are thing patients. a it, excited

Operator

next is from Goldman we of question Salveen have The Richter Sachs.

Salveen Richter

With the low-dose can update where what how then this in new seen regard the to process secondly, on had regard here frame thus RMAT, you're on the for forward? thinking understand midyear basically so from we've regulatory the of us And far help benefit about cohort, with just us maintain or context benefits the you far? the to you've

Sean Nolan

thing, Salveen. Sure

expect, So update we're adult the going in what that midyear to we've patients terms to so dosed. X of give an on

have share as clinical evaluations patients an off that And been would be again, at and example. to observations work we'll this done. most both So recent time, steroids the of

give wasn't adult shared with for over available we've to most that on fulsome well, this study -- to it observations tracking it's the that provide could of the information and And think we'll are possible as we'll of we how today the terms update part shared in same we data the endpoints recent try a make course date, we've additional very relative both some show So as midyear sure in of clinical they patients. collected the to pediatrics, highlight time. the the have update the and that we of

give do to And have of want across in there's over good of adults, so multiple what able what we again, to seen. back really landscape date, you time shot all we is that the consistent a course we've domains. what outline And been been clinical is to

motor So aspects, gross function, and socialization function. communication seizures, hand the the and fine

the pediatric of a patients going have you across would domains the want regardless direction that, low for provide of dose same right we X of their are at -- type in to All to both seeing pediatric the for seem patients. patients. And effect be movement that We these Inovar first type the win genotype. consistent for

we're relates of reasons. it excited number As about for this a RMAT, to

the that First is including level. of you to FDA, a ready fantastic very access folks all, at senior get what's

can we're you've of very with and what's talk think the because through endpoints things good do design the got trial just more to feedback such as be early we what you on. get their want might to collaborative and So opportunities we much that that, seeing

reducing dramatically obviously that regorational in the of of and in increasing a And the of amount trial. probability time can terms success potentially

granting for agency us. the you meeting to thankful XX your particular designation very is are What within is that initial we them. to about do days So with

And have So and full again, as thinking. their thinking but things. -- generating we're pretty enhance with it [indiscernible] it, we'll our the very early will to further this going able nice we into we're relative be think this on, data, FDA to will aligned

RMAT critical Suku of designation. think that aspects that considerations and probably aspect garnering I additional outline are you didn't if let But the think to the most the ask communication So able talk important. I there's that you're are me who to

Sukumar Nagendran

[indiscernible] what comes company you've sponsor I initial the to you officials they thinking necessary. FDA discussed contact senior the as as And product the data what RMAT understand the be FDA to the program within the ground on our of Salveen. far to else if already a accelerate to gives done and what are mean, as based when on with actually obviously, allows it also Sean, the with earlier, closer said and much it I the

the So unmet there a program think that process essentially, our in this is medical is when patient it's designation sponsor that created mean allows make population, especially truly difference accelerate going to a we need. a to significant significant that FDA I the

will work So forth, said, the program teams I so as closely and manner. rapid to but meetings an when appropriate move FDA very forward my in and this CMC clinical to with comes the it

Sean Nolan

that's only our other is remarks. that it's based Yes. important would add The clinical I other sharing. about think But we RMAT thing is you're preliminary granted thing that I it on data that highlighted the in

that's from there adult that X-week X patients it's very an the a share sensing a so it was of population And the a patient think also asked is patient, potential about we patient a disease. data. suffering pediatric data. I so I objective pediatric the indicator -- from the could the And party third to that believe worth question benefit be Kristen

interaction agency. we look So the have the with again, we're first to pleased and forward under RMAT

Next question, please.

Operator

from we question Whitney is have next The Ijem Canaccord of Genuity.

Whitney Ijem

add loop data regular they congrats Astellas. kept like extent that the they being of are And session? in -- being does is what RMAT. there us on communication I'll like? how to sort Or my you are a Can on sharing I what the day, question guess look my or around quarterly is remind

Sean Nolan

of mean our Whitney. the I remind so do we Richard an there's around everybody Board Sure, observer also But that I on the he in have to on, team. time, Wilson -- updates quarterly structure the would Astellas team Board formal he's Astellas as just members aware is updating that real that. anything regulatory if in that. we're are we're having can very participating interactions, say from obviously I

clear that's key about data the with So in communications being I you would say are there's Whitney. with regulatory generated strategic Hopefully, that helps shared. a and aspects Astellas transparency being authorities program very the out, that of

Operator

Lee line. The Chris Piper The of to response Raymond next have from no that Sandler. is we we have seems from Instructions] Truist have next is from It Joon of question Securities. question [Operator

Joon Lee

and the data on Congrats progress. the

event hold dose? the the conference, XX we You're plans have low the on initial scheduled webcast in at do pediatric investors? you when data to expect present any [ for data that RET to is June a a can ] And around

Sean Nolan

X. there data update some, would adult but That give have cohort on and be [indiscernible] the pediatric be we we where yes. on the Joon, update will have communication, -- to like Yes. the the platform And we'd the the

Operator

next have of from Maury The we Raycroft question Jefferies. is

Maurice Raycroft

progress. the on Congrats

which pediatric Just much you follow-up saying say a update total have question year second patients? month initially. clarification Are how the you'll in can you patient? Or for the pediatric the dose you

Sean Nolan

second would is we about I likely we that what for would think believe most for specific data, weeks patient. the second that patient. of date But pediatric don't I have dosing have X X to

Joon Lee

for it. MSLA midyear that the show data, Got clarifying the the the pediatric pediatrics measures for going you're there efficacy like update. unique any in measure or to specific are And also measures

Sean Nolan

adults, through the we'll that we're are mean, measures through -- the you've I still presentation. they're that I would be adult our some the we they're things part working information. study. to that the haven't that that so share presentation, to because shown date working the can but say there of not some could you still seen We're do best tell I on

on I'd stay collecting that. working and through So tuned we're stay Maury. simply say this at more again, because just it the tuned But for data all point. on that,

Operator

is Raymond The Sandler. next question Piper Chris from of we have

Christopher Raymond

technical the issues about Sorry earlier.

But Just chatter we've this competitor intrathecal already, I may for market -- that apologize, got brain versus administration impacting terms uses be advantages asked relative we've program, folks in the disconnected. some if got disadvantage around there a some heard of ICV. which I of XXX And be heard might positing function.

seizures. of kind I'm guys early in curious clear pretty functions, guess you autonomic even I seeing about improvement this, communication-moving some are

have and the data follow-up. in distribution. remind -- the broad us that that the gets of that a broad strokes, vector I just brain has then into And maybe have So shows you

Sean Nolan

striking threshold Suku what would the take this to, a Suku impact the trial been could I you PXX trial I'll [ likely ] a over think and mean results it ask -- produced. think then and done right I clinical lesser mice ages have did to There's mice, preclinical would in really total you think say can when And the see -- I you -- We've here done you the MECPX in disease. given of the that the to ICD. in biodistribution other at but right? thing all on very X that just gaps a most in path, for it, on of work also to fill I are we combination that's dose or and take in I have done is intrathecally preclinical therapies important TSHA-XXX that, point you're question. work to I different different where Yes. point some of gene right? or and X get -- any it's

be different if looking socialization, at should with being affect the -- you're impact, the saw motor to to outcomes are at you're as that phenotype. of gross to PXX, X right? trying very importantly, right? good PX, looking we've reported the everybody -- like the different of those with seizure brain, mice areas you're again, wanted and speed, we have most thus at I it's And there clinical looking far coordination, is think domains share reasons clinical hand So looking the we harder route. But right? are function, And P-XX, the all affected, those well data intrathecal fine we

designation get we're be So And distribution impact with there is and has level clinical it to and to again, point to unmet very the I'd preliminary high enough need. disease that threshold a the have efficacy some in to RMAT seeing. the demonstrating

indicate whether But the one that disease, effect and that data to it's route you we're time. of evidence understand the I of seeing the another. But XXX real has that add. more I academic importantly, preponderance may significant would Suku, a go So versus preclinical discussion ahead. the clinical Please think or on in more have

Sukumar Nagendran

The thing out add it's disorder, gene him other you or but I the to lumbapantia. point neural good be adult is Sean, syndrome would explanation. only gave is quite the with I that by to developmental both just Rett this patients think And rapidity which maintenance Well, therapy thought a given a network a disorder. reason not is I responded neuro our

comes days this therapy. with these XX getting So corrected dosing post especially function, to gene outlining when it

may of I really to gene so with this regardless with therapy need you It's [indiscernible], -- -- guess, distribution. raises understand So the of question that bio another disease. trying perfect never the the pathophysiology

it in of the other extracite, when in -- are -- these are thousands gets neuron some genes or deals my transcription every silenced while or MECPX actually is prevented point appears is is activated. genes of so So nucleus of

that's you seeing And kind up patients just is now. getting and restored. starts guess trouser this brain the So starts picture what I'm your like I to then of getting dosed MECPX playing think what up him sick that function of adult conductor. have the make contract till we and him, restore where at is And with conductor entire we the [indiscernible] are once

Christopher Raymond

follow-up. and a Maybe just --

some tapering there maybe the I was last and the that of think the you when here RSBQ teasing on as patients? out tapering progress or around that the you continue your in steroid fact impact patient presence, discussion guys update, X. Any you dosing on improvement were update gave steroids

Sean Nolan

case patients treated off going can high look of tell effect. to as I are feel initially, We'll number patient to that steroids. patients other jump the that to therapy. that there we was on I we've I there's are be period were to steroids to think steroids no very highlight have of because that of benefits But you reduced steroids at And gone, of one, Suku, they're one. X mean Well, demonstrated And steroids thesis we here. result masking is time it on to the patient, mean that seeing that see And or we I we thing. I that treat had disease, But the uses that may to actually that the is of loss And for a the and benefit the the is free the have elapses this same think was them. we've interesting. But What made everybody the tried what you, not a dismissed irritability X the hard a efficacy of we wanted show date, time were no I when is, one that. was at think, to think see there that number see side if steroids. some say in to it of that showing I after I more dose. with diminution a would anxiety n a long been she as

that actually a And ability your in have terms girls reflux, it's cycle, I to steroids these right? removed, think an back are then I can steroids feel having an that when eventually steroids update of a lot on they've which caregiver think particularly you because it be irritable if And about we positive well. that the being be too like And So worse. as sleep dealing see bad and negative of been it, down you durable make like to well, where irritable, with things. And are doesn't provide child RSBQ, the the there probably tired then were very and right? outcomes a masked, that may they're that you can about believe

more So But We'll we're be then have case. the thesis. Suku, help patients to But accurate. seems that would make. is to anything distinction trying add one? you'd steroids I that the to think to come as else see And support that's certainly, I that totally if off think that that's X there patient

Sukumar Nagendran

the the Not much going effective short I are we else, them, it's be. Sean, [indiscernible] mean, of learning you as is the to -- use think I what and pointed out, more

Operator

from Gil have of question & Needham next is we Co. Blum The

Gil Blum

And again, congrats on the progress.

maybe to -- follow-up. multi-domain mean pattern similar that. I Some [indiscernible] there understand are very harping help right? a mean, And here, help just a indications, is what by So have activity? of patients a just but of understand me me do I guys bit to these

Sean Nolan

like the would of I things. types seizure updates endpoints thinking fine those -- [indiscernible] think but if CGII, mean like domains simplistically, and CGIS, of with also function scales, and speed say aspect very and going about you socialization, I function, measure sure. on about and Yes, motor the we're the give to RSBQ, yes, those it's the gross

group, different area that adults further, again, highlight you we're the always you what to similar say important trying it's have severity in patient a being affecting we've affected years. and there's paint But a And as versus to least domains, to going of mean something thing very they've know, it's another. just dose. [indiscernible], patients. these in us, and to across I for similar the want disease disease show to pediatric we're the one fashion that so present if this had -- They're same there, the more areas we're low multiple snapshot less can each or the patient in X to to many seeing it's of tried we're so each for disease the for hit the domains X, just Suku, in please do. at that So fact terms

Sukumar Nagendran

No, guess quite Gil everyone, Sean, where an I complex is lot. to multiple a presentation mean, does I a normal. I And balance know, as the and -- is really this you remind have a as pointed disease aspects of phenotypic think out, don't the syndromic made add vary I very

impact are when gene hope to X of to the So the syndromic is you to regardless I able [indiscernible]. approach, that restore comes the replacement do intrathecal function, of it my to mean presentation. the

then our accumulate proves we So that as hopefully, data, point. more

Gil Blum

All right. It's very helpful.

in that that larger there what the will the any guys before. functions, learn adults kind I improvements discussed than they about we've be Now is believe to [indiscernible] functions mean adenoma in How seen not of in but reason patients. maybe you are potential younger

Sean Nolan

to you take Suku, that want do question?

Sukumar Nagendran

Yes.

Gil So -- what's Sean? that

Sean Nolan

in patients Gil was asking versus my autonomic function have a faster or improvement greater an improvement pediatric the adult.

Sukumar Nagendran

rapidly is safe a to it's I automatic we probably mean outcome remarkable assume, tough time, point say, in that pediatric those would if XX for be were correcting think dysfunction given a in [indiscernible], kind this population will are question. at economic this corrections the That adult patients, of also therapeutic that I days, within the intervention. in do able within I to we X

don't half can the it know. in segs as Honestly, caveat you time Now do I the

are it time, think XX don't X see and patients the it I same difference dose around. least like, what made or clinically, to of in days. dysfunction, response, the the in picture, X much we in where say, you happens. the features versus comes that of days Rett aware to at get rapidity have at a addressed bigger autonomic We we syndrome when But of

Operator

The Wells next question have Yanan Zhu Fargo. we of from is

Yanan Zhu

I was and even you there you greater what for I incurring follow-up. mentioned at could -- heterogeneity i.e., phenotype the Since in the treated to have level and of therefore, X baseline, potential like, wondering young see be of patients effect the severity an mild a less the are heterogeneity, far caveat Great. then patients. so very

Sean Nolan

take please? that Suku, Can one, you

Sukumar Nagendran

Sean. Yes,

heard a beginning, -- to the the heterogene, pediatric population [indiscernible] heard At I the tends with said? you though. I the that sure make to want what be just you population think say I question I is lot that I compared assume more So to advanced

Yanan Zhu

of you for highlighted Right. I patient remarks, I thought the pediatric I'm just variability say population. the prepared in disease heard

or if So benefit. dosed be they disease baseline I expect far. to for that levels? of and what so to there could benefit X you difficult have severity see it's there the was so -- very high therefore, demonstrate that context, could -- there have reasonable any -- patients, some for mild wondering, patient the to be reasonably are X Are example, disease in may a Is

Sukumar Nagendran

think age, you when I heterogenity if so to with I but the syndrome given regardless Rett consistent that, a anticipate comes at So right? gene to having that -- presentation, therapy syndrome, understanding -- expected mean so said the board response across my response, a at never by think is syndromic what look would clinically time, is and it where I that regardless you take the patient when the of complexities most adult patient age. response of the the patients response rapid X a sustained has present we shown of

baseline of obviously, So data characteristics patients, we disclosed pediatric haven't the yet.

clinical tuned. features should stay is can board. So higher go the the that and all syndrome I say is of the we to door, the consistent of you across effect my be And the hope regardless have as

more autonomic I question. -- address we I to in I answer if you network respond is hopefully, can seen mean in pediatric has are, the a help young don't anyone gene even quicker. the only I think where done Now so guess orders discussion to should concept patient a as other the we think And the is pediatric thing again the gather population, is obviously, assess that. therapy that data young,

Sean Nolan

that severity. the that, okay? other see thing very is CGIS to for trial Yes. severities that similar the to X, range you're in in The protocol, to I it's X going to only similar say would So adult the is basically, Yanan, between

Yanan Zhu

and patient Got Or that the has about then safety if That's And evaluation ask may wondering, the is #X, on the to was reassign for maybe the follow-up patient still something could still patient a low I patient next dose? for I or have you cohort super this -- that accumulated. with down helpful. upcoming? IDMC the to you patient, perhaps adult plan third been what yet? And is do you similar based the higher that Or it. dose is did to the dose data for

Sean Nolan

Yes. question, That's Yanan. it's a good --

has answer the X IDMC patients, next I to question think things. patients the to IDMC. haven't to It the And the and so it's of would go the to of again, in on evaluate any I yet depend not dose observed -- also combination who basically, weeks. you is your certainly on for and to efficacy we the after couple with And will met think the start safety only coming high -- going talked and

and I'm just you I'm a just into their patients like pediatrics, it's dosed see well, example. of They we say, because pediatrics. an simply what So saying. third don't giving could read wouldn't

the things a lot logic for how have data makes play and presentation will So with the to out, IDMC. of as We'll it your sense. just start see

Operator

The is Allen we Jack from Bird. have of next question

Jack Allen

the on Congratulations progress.

of Just it mine X similar and last of as of here. quick it question of next que genotypes, data asked a in patients, lot phenotypes pediatric questions about kind to X But of How I from patients the the going know weeks as were as the these was here. were X you what the from have? anything get that to these say relates patients genotypes several can me

Sean Nolan

Yes.

want that. do to you on comment disclosed haven't that? But We Suku,

Sukumar Nagendran

got I So question. the make just sure I want to

patients, right? X the in pediatric So

Sean Nolan

are Right seeing missense deletion -- like mutations. a we significant seeing --

Sukumar Nagendran

So I disclosed the I I genotypes this -- mean, in can point at time. when haven't we guess,

much I in mind towards too What side. you mild and patient recovering sick patients to so is that places can mild detail. without severe assume or forth IS into do and the how I other So now CG, tell are. And going keep they more is evaluate see X

we for to therapy. what a as anticipate with you has so a if to response a [indiscernible] the patient mysense what mutation. And gives even would that's also a that phenotype X a observing are feel clear mild someone due is But as a of

say this their was of patient had that seizures X reason think you if who of remarkably in [indiscernible] adult gets was is well. the multiple had I a actually our -- seizures was Canada, second week. a treated Some not symptomology too And dosed And patient antipleptric. and

been the by doses and medicine have decreased XX%. be to appears patient this seizure-free [indiscernible] Now

draws have question parallel clinical eliminate the contracts patient hope hopefully productive a I such you that the address, So which The patients a can XX table these guess and then have much or can gets I stronger control because different of on features. life. becomes that

Operator

have of we Tuerkcan from question last Citizens is The JMP. Silvan

Silvan Tuerkcan

Congrats side anything on that heterogeneous given I to the that -- will is there the have consider question comorbidities, vein, safety pediatric the on patients, more RMAT Do they also here? on be have designation. please? a anything the important in that

Sean Nolan

any patient and clarify wrong. heterogeneous adult... I'm just would Sue, me more I than Sure. -- the The pediatric correct isn't if

Sukumar Nagendran

[indiscernible] of my That's to knowledge, Sean. kind

Sean Nolan

question. Yanan's on comments any Suku, And Right.

Sukumar Nagendran

repeating mind So do you it? Yanan, your question,

Silvan Tuerkcan

sure. the They're Yes, have smaller there's with side that if in toxicities, adolescents general, don't smaller wondering levers, maybe may I in on patients have was we of. but comorbidities aware that pediatric also profile just safety to anything that have. be

Sukumar Nagendran

No, DLT, liver And detail but think the highly elevation been giving know, program. and blood dose, that that compared the activation a an in which low and events where But the that's [ because ] any because that count, given such XX% systemic to antibodies highly seen it we highly as therapeutically circulation, that's before complement launched a dose, unusual get tropic is good have we're does in into systemic unusual, if discuss question you to great -- enzymes the AAVX made in XX% unusual. liver, T dose, this in cells highly did is intrathecal pretty intrathecal and we we intrastate change to with is ever, about thrombotic unusual, to the low dose being transcend goes.

gene But common. there's again, a from is point also standpoint, my guess [indiscernible] I not therapy guess I changes. So it's

you the refill outweighs for benefit, the think, risk. So program, I the if my risk-benefit do point the far analysis is,

so and any concern that. And -- we had after

Operator

closing the have Sean for the session. comments. over would floor end I like the of reached to We Nolan question-and-answer And back to turn

Sean Nolan

this on Cohort here pediatric X time the you adults X Just the all. data and for thank providing well next as further everybody night. evening, both as weeks updates your Have a we look forward coming available the the in to for patients. Thank good

Operator

today's joining concludes us. Thank This conference. for you

You may lines. now your disconnect

Taysha Gene Therapies (TSHA) 14 May 242024 Q1 Earnings call transcript