TSHA - Earnings call transcript Q3 2024 | Taysha Gene Therapies, Inc.

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Operator

Greetings, and welcome to the Taysha Gene Therapies' Third Quarter 2024 Earnings Call. [Operator Instructions] As a reminder, this conference is being recorded. It is now my pleasure to introduce Hayleigh Collins, the Director and Head of Investor Relations. Thank you, and you may proceed, Hayleigh.

Hayleigh Collins

Thank you. Good afternoon, and welcome to Taysha's Third Quarter 2024 Financial Results and Corporate Update Conference Call. a ended announcing September issued the results Taysha quarter third XX, today, press financial release for Earlier XXXX. our A is copy filings. through available release SEC on the of company's website this press and

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

including call, from durability results concerning clinical fourth the a making or initially dosed of forward-looking receive be any candidates, expenses into information. question-and-answer results hold are facts for alliances patent expected property, prepared reporting and the discovery well Taysha's will those and will growth, for trials disease and statements to contain of stated as following development development materially to patients the life implied in trials product clinical results programs. This cause cash also our as for from or administration of and seek third-party to matters and our remarks. Please results uncertainties and requirements may interactions related parties, to research, development our of product plans clinical for and cash including intellectual our current obtain alliances These capital runway of and call approval forward-looking trials, the and we risks planned ability our imposed and regulatory for regulatory clinical candidates limitations discoveries, from conduct not regulatory that and the and the statements our foreign data our seen candidates and research those and patents by requirements to supporting including and these regulatory future risks third differ the market note opportunity clinical date plans favorable candidates, actual additional Taysha's positively controlled in timing and product in our course We session our of product of substantial who the other our and and to may that potential or our FDA regulatory the agencies, resources include owned of timing funding in results, operating statements. to include equivalent relationships, our These other strategic of clinical XXXX. potential strategic protection activities. of to relating trials operating product initiating timing TSHA-XXX, the trials or patients to such impact statements quality the for historical on treat, reproducibility the Various alter forward-looking of of upon forecasted may dependence quarter candidates, today's potential intrathecal the statements, by

may Nolan. this to information of update call that would XX, and XXXX, call our on see laws. With CEO, the Exchange applicable Form in time-sensitive be Commission, November quarter and on filed XXXX, ended Form broadcast, description or securities reflect obligation XX, year no conference For we reports and December for the the the of now over to to that, have filed September this with any face, as the is call, risks including contains by our that XXXX. turn Taysha after conference XX, XX-K except revise accurate for the I of required circumstances full date Sean our forward-looking report to only ended please quarterly of date the today. This undertakes a list we like live or that the statements uncertainties we XX-Q Securities report and events as annual

Sean Nolan

Rett and a brief then to update Suku you, will update recent then Thank provide syndrome. continued for activities, for conference remarks third with our call. Kamran I financial follow provide the our R&D will and closing clinical for begin drive on and and everyone, program open an adult and lead to third clinical and and TSHA-XXX TSHA-XXX up financial up results President the corporate on of our call and Nagendran, evaluation Hayleigh, Head with of welcome, our XXXX Taysha, quarter will across Alam, I Chief questions. In will update syndrome. with adolescent update. program our quarter, Rett a Financial we pediatric, progress evaluation Officer, patients

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and saw which we analysis in ESGCT studies pediatric over of of to Congress in-depth RMAT the on recently in consistently the reaches clinical both now of of areas TSHA-XXX what early, to the Suku dose disease intrathecal to the focused date and impactful year we REVEAL in construct was from the as we gene of X data REVEAL the expect longer-term differences mechanism pathway plan see is improvements key treated with for the multiple Importantly, and Annual FDA reinforced believe and remain and gains will and Suku brain safety reported provide turn demonstrated more and functional totality cord. discuss trials, believe working of improvements look we we encouraging with reporting delivery and have despite efficacy has based cohort spinal we to low X adult of cohort for a the presented strengthen ahead. I an TSHA-XXX across depth. Collectively, execution patients severity. to the closely that Suku? and this at X first over the design as therapies prepare through more XXXX. potential we low-dose We the in contributed this that regulatory to the ] time strategic will high-dose solidify the that new in be mature, forward the data we data sustained translationally with our data primate there to nonhuman from We call half to in baseline This discussion trials both the [ TSHA-XXX. of from the on continued to the data continue domains. data, demonstrating

Sukumar Nagendran

in good Rett TSHA-XXX our for gene Thank I'm therapy you, Sean, clinical and afternoon, pleased to syndrome. update program everyone. on provide an evaluation

As we we Sean over for achieved the have believe TSHA-XXX quarter. mentioned, regulatory important last progress

completed is of Questionnaire, the and on hypothesis trials. is Part for the Therefore, in our advanced generating, and to our A that potential for intentionally reminder, pleased of our data next with established the our Rett to REVEAL inform Part to RMAT natural measures meeting intend phase find with endpoints, Part of objective REVEAL for data trial a across of Type for endpoints this A on TSHA-XXX. Syndrome to focus inform designed I'm Part our multidisciplinary clinically help reported as of discussions with approach generate ongoing development plan. in the our the to a trials from multitude Behavior not We caregiver studies. We B elements to forward pathway recently share FDA development be secondary included FDA. testing, B potential an final agency the data B a history of design, regulatory gains. not the or key TSHA-XXX meeting the collect trials. plan functional discussed RSBQ, As that productive, use Based endpoint or Part was feedback the the trials we was our regarding as of and ongoing an primary with on In discussions, alignment to focus, FDA capture the set very will we B hypothesis line will use continue

the completed readouts FDA, meeting in with TSHA-XXX. and to existing a recently pivotal analytical to use We package REVEAL our product our the We cadence provides reporting trials. of the of development commercial aligned REVEAL clinical also for FDA demonstrates and our our methods progress meeting B. It release plans, share pleased of on BLA product as I/II the completed endorsed use with FDA scores meaningful product in the also the we from CMC Part final the process for Phase B. is of use product and be the nonclinical released action believe release for the ongoing data analytical adequate Part will future I'm support B readiness we manufacturing feedback expedite FDA proposed intend including trials. The Type a the B our on Subsequently, and to derived longer approved REVEAL corresponding development further this FDA towards with between evidence pivotal demonstration of qualification trials BLA our mechanism submission, the product, no confirmed the part and process. RSBQ to plans of validation scale of TSHA-XXX The successful final comparability Part data in potency the commercial CMC which we pivotal assays. We and submission in based

Importantly, to the future plan to the trials believe Part RMAT with the based FDA pathway potentially We forward this for have discussions our closely FDA clinical progress our data. BLA provides the data totality encouraging. mechanism a regulatory our continue of utilize through TSHA-XXX solidify to the with on A in Collectively, submission. we working path of from the been

to turn clinical let's Now our progress.

we Rett patients Stage U.S., REVEAL and place TSHA-XXX: with ongoing trial in a and trials evaluating older Rett Canada adolescent X Phase and and years the for X III reminder, IV taking trial syndrome; the to XX I/II have the place Stage in pediatric U.K. taking patients a syndrome. of and X As U.S. with An for age Canada adult

continues the enrolling REVEAL both Cohort enrollment of trials, in of of low vector levels weeks adverse the across evaluating toxicities high portion genomes, or X.XEXX with generally X, TSHA-XXX of is A, is total X With dose-limiting as currently progress XEXX dose for adolescent no we've treated. X patients TSHA-XXX. first the and both pediatric trials, X Part which the XX made well-tolerated adult dose total dose vector events high to of for of first dose be the TSHA-XXX are X and weeks in genomes. The patients at of which We the dose of substantial evaluating escalation evaluating Cohort complete patient X as serious

of IDMC this cohort we continue trial, pediatric the Subsequently, patient the with enrollment Following trial in the high-dose current high-dose in second and dosed we for with cohort patient the to the adolescent/adult of the the third the review high-dose approval received in scheduled of cohort. quarter. enrolled the data, dosing we

to brain trial for sites trials clinical also recently effective, targeting further our further biodistribution Part of additional and minimally-invasive annual delivery delivery preclinical central Congress. the both We XX AAVX of showed comparable, to we therapy delivery safe, presented data for TSHA-XXX, the B an potential intrathecal, at the widespread ESGCT magna Data collaboration across administration spinal as intra-cisterna intrathecal lumbar, X of approach both clinical led primates supports REVEAL activated AAVX analysis for readiness. In that throughout cord broad support evaluating delivery across and approach the intrathecal nervous gene the from and biodistribution consistent system studies regions. human vector of and that

safety plan us over shaped discuss and provide reported low as the disease of we across data believe turn our translational Kamran? improvements a Kamran we position collection for demonstrated B regions high strongly to studies. I we the key of our discussions financial data both trial will for plan, that to at that areas well-tolerated developmental trials support the seen combined have solidify Importantly, have for success call our pathology TSHA-XXX encouraging further clinical across our our Part -- clinical impact dose, work brain. We results. regulatory of different REVEAL and to execution the the now with developmental that these the that clinical of broad supporting known continued findings profile continued to are

Kamran Alam

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

XXXX is loss this million classified $X.X million and with September for million to for The a consultant months XXXX. higher August compared administrative or the Additionally, for to of the the X in XX, due of change XXXX net in ended expenses non-cash million, a $X.X the XXXX decrease XXXX, primarily headcount, offset August employees $XX.X $X.X loss allocated primarily of the of contractor XX, was XXXX. and from the in expenses. General was X months September for The to associated months XXXX R&D for a with liability by to to compensation value the loss were in the a reduction million, XX, or of million the partially liability warrant costs XX, was in ended September months due XXXX issuance XXXX from associated increased prefunded lower compared loss reduction $XXX.X net per fair warrants reported warrants September share, as ended share, result financing. $X.XX XXXX, ended and pre-funded financing. Net $X.XX $XXX.X X per X

in cash into the XXXX, planned his current capital cash of As September its of Sean expenses $XXX.X support Sean? closing now back will requirements for had million cash turn XXXX. I will Taysha resources quarter to equivalents. remarks. and expects over Taysha the call that and fourth operating XX,

Sean Nolan

Thank Kamran. you,

for progress Operator? B across our expect with option genetic an be Rett program, plan to we the trials the from of Rett possible. With to will we low-dose therapeutic that, we We solidifying discussions ask we and steadfast forward made the to now continued both treatment work across as syndrome and remain and to for Q&A TSHA-XXX Part with of development cohort ahead, We year authorities data severity. expeditiously to with We are regulatory adult, benefit safely session. execution as our to look bring new longer-term continued mutation cohort I operator adolescent, syndrome which as to potential a prepare remain patients reporting to is data patients as our include trials. the from with what clinical REVEAL on in different TSHA-XXX and high-dose and development in impactful planned begin and the pediatric pleased provide the confident focused

Operator

first Fitzgerald. [Operator Kristen from Kluska comes Instructions] question The from Cantor

Kristen Kluska

this productive it you. objective on quarter sounds how thinking I you the measures, the side. regulatory endpoint for Considering a focus on very It ask broadly to are more wanted it that in could heterogeneous Will like could one was personalized, areas it covers be disorder? largely broad a about or focus the something is this few that perhaps on specific that's a and measures? context that

Sean Nolan

for the through Thanks the I -- have you into take this. definitely heterogeneity it's say to Kristen. question, would consideration thinking as you're

think of example point, endpoints, do looking so the need own good at loss and we've mean, -- look potential to having you patients, some have that the as approach I milestones. specific evidence if I as gross certain forward you them patients we've of would you very supporting would at you about One And it actually put analysis and market And across be point, every looking potentially, for a right? color. gains, measure endpoints. And function different milestones patient thinking kind going expect the we and your that gained aspects the our very at to I can about to meaningful are can an and of may across to very I FDA trial for also this a very to be of consideration something standardized of little you to design types gains. how And yet motor think broadly you disease, discussion Possibly preliminary of a of bit or of this that couple milestones from of have never high that, demonstration, be designs. think would never different each week. I think it have gives a you control things about to function, earlier potentially lead different think functions thinking is consideration. that also their about next communicated think patients in is that taken be patient the objectively patients. Hopefully, trial seen have all or this we're could if of history with and are to the as effect can and these consistent you potential I'd these history, very but that's buckets. our consider specifically, completed into hand integrity into functional types exciting those, and natural a clinically data consistent that to natural that, And could can restore

Kristen Kluska

Yes, to And then a the And compare comparator will potential hoping get a it does. more as for about I our natural analysis. that, just bit on little then using it the completed follow-up around thinking be to patients context here, history expect of in broadly we're many based are seeing there milestone any and these trial? to stratifications or kind this, it Y of achieve on just could was X

Sean Nolan

level. high want to it a keep just want at I Again, I to Yes. --

think natural distinction followed could the extent using in history you between a SMA, is type the say similar X like what as comparator not a would progression. That's here. all it there a I to indicate patients

very aspects when consistent seems or are as people be of function lose certain gain there to never However, disease, well. the including

there's to with discussions forward again, here the think path but and that this the to FDA had preliminary a think next later in carefully, have We've about discussion, on we quarter. we hopefully, So steps look here. forward in

Sukumar Nagendran

of evidence, this in will an one also thing clinical the role state. also Kristen, is I I think, disease add And totality important play would

you these it's As and have features. patients clinical out, heterogeneous many pointed

Operator

from Chris Piper comes next The Raymond from Sandler. question

Christopher Raymond

very been a out that your you had just with way safety they saw the and looking had talking and guys are on It update questions. from it just of language patient weeks couple today looks I'm high like was Neurogene's that were they with pediatric showed X just the that Maybe X and adults patients. seems SAE you A up XX at it been the from recently dose. dosed? guys least --

Just SAE. clear? thinking follow-up. And a in for about a Is AAV-related be the the might think have range an maybe I patient a window there when you

Sean Nolan

X dosed I'll patients. over to And safety very be high-dose clear, was dosed. patient reported Yes. and the just recently in to turn because X now it we've Chris, Suku, fourth We

to hit So turn yet. But I'll your that they question to Suku. answer didn't specifically, over cutoff it

Sukumar Nagendran

based what Yes, experience other mean, through Chris, is well you going systemic of include my intrathecal. gene I alternative on which walk to as routes, I'm kind therapies with as both

So keep these intrathecal/ICV, eventually of might population. dosage the clinical become that could this an you its mind patient some reactions important in given in in factor see that with

because have or right? but with immune you XX% product the exactly XX% can liver an following, an for tell so in result get tropism T mixed idea Neurogene antibody reason, to can to or of response, ICV, T With significant program, again, elevated can I get forth. no systemic you liver. I the So the and into And what to intrathecal, if And is response circulation. XX%, whatever there's that enzymes in XX% happened sometimes liver and what AAVX that sometimes the cell has cell can response a the immune about

sometimes the the the guess, role the play in response. And product itself, can a I purity also product immune of

keep else something to mind. in that's So

surgical symptomatic an of on immune concern could be of brain. the cause standpoint, they and knows causes ICV some the that sometimes that inflammation a that in ICV cause if the the may we a when or that immunomodulation. you this part that than better needle it The though cause impacts I'm Neurogene that within do second can the an product, procedure, can damage an obviously and do even the is sure procedure also And itself, spillage do, from trial. response And when brain patient triple

TMA, can intrathecal The mind into microangiopathy, seen with do other when keep product but unusual get I've called thrombotic I think a as DMD, past to an in pretty times ICV component it's gets circulation, which many approach. the the is you systemic in you something

that's cascade is they obviously, that a results something what that cetera, and et if there's TMA here, affects response, got be wait cetera. then get of can there's then that -- also activation the system the the tends et activated, kidney, immune entire So to to an the going the in liver, inflammatory systemic in which result can response to on immune complement it But with you see us. share

might else purity to not that there and the of something this all -- of, back the aware circles be product. we're So and

on all cannot you I speculate about at the my that's all. Neurogene can But past I with again, experience. program, tell So based

Christopher Raymond

just that discussions FDA on, using FDA. and gave know -- detail RSBQ Cool. lot you then your And a Okay. not I in on with of

is it -- variable, endpoint trofinetide. a Just it you but was out. co-primary -- as Maybe for but guys have pointing also been highly

from that? as to endpoint? paying any in actually of reaction terms KOLs docs of sort RSBQ reaction on reliance or Any attention an of that? Just use sort to Do the

Sean Nolan

did. tool KOLs, would Suku very, I they would the which with It's and view RSBQ given is not for was a their designed good to to to measure never is And that this. use to that to are in to if by all. that thing our have it, go say I first at trofinetide the with universal control is purpose. a And to highly you're can a what discussions tag-team idea say, in for is it I therapeutic going variable. fact going intervention It's you're clinical use caregivers. they try it, placebo

-- they're of on instead this at type they're clinically very with these actually supportive with we've endpoints. objective meaningful the focusing had looking pleased So FDA our and discussions that, the in more some and with discussions KOLs, of

Sukumar Nagendran

III you are product which gave point a that frankly, significance to I composite, my RSBQ. was think that's had be know relieved added and was as many there's subjective. CDA with pointed measurement force there vary some of what it. a from I It's guess if p-value that why caregiver-based that to Sean and said, for day-to-day Yes. I appropriately RSBQ by a well variability, they're what the would trofinetide, on can is, think, not at much I clinical allowed, original driven reviewed the an I And us, that already much trial they as basis. to remember add too also and the out, and I time. But a KOLs using as that again is of Phase CGII Sean, who then variability. point in And is designed both that make it felt reviewed RSBQ, And endpoint approved the think And I'm you aware trials, driving very scores, of their too

Sean Nolan

because behavior the a done is because in past aspects the function when given the measures improved guess function Yes. the looks the RSBQ have than the examples Chris, mind have is and think of function in we've where positive. certain gets the like point, function. behavior has behaviors couldn't And I keep multiple that worse, that just a -- people last that rather they didn't to itself RSBQ I be negative And

that to setting. So type just use in another scale reason of not this a

Operator

Whitney question Genuity. comes Ijem from Canaccord next from The

Whitney Ijem

Hey, as from guys, the well. progress all congrats on me

high-dose well. be in in or But guess, the eye ultimate -- and of obviously that in with with can you you from an enrollment demand through thinking opportunity hearing level demand if the or patients is characterize the interest of wondering study, adults seeing? particular, in older kind the cohort towards I curious, the of going market Just might really kind

Sean Nolan

there's we've mean think patients over I I had and a oftentimes, both you younger they're multiple community protocols. cast that mean pleased the with I -- had the wide start very we've it's from that population And we've then we've Yes. such get slots demand. expand time mean, into significant -- that possibly. to net. I gotten in a wanting feedback

they've treatment think fact the approach appreciated I the the take potential care we're suffering to of patients a Rett. offer from all that and and consideration trying for

Whitney Ijem

of guys and which lastly, on us like you does treatment? immunomodulatory logistically regimen? a does helpful. point like of Neurogene, through differentiation the remind of what Got between When patient you it walk the And us day clear route point administration, from to start? it. and that That's look what's patient the a like just treatment, And around happens what is a timeline-wise perspective from perspective, then can the like relates as

Sean Nolan

You're talking the we're immunosuppression protocol? that regimen using in we're our about immune -- therapy that

Whitney Ijem

Yes, look patients? kind like these what treatment does that, of like day then just and for

Sean Nolan

day. Treatment

Okay.

Sukumar Nagendran

a Okay. I Yes. moment. for get it

you reasons. the different So patients we when with been really studies, responding, many for started for protocol if as originally is our the such don't that a were we procedure But gene the got it. was are the they And we sirolimus, how duration. longer because much we -- but experience we've right feel need immunomodulatory recall, that shortening the patients more and our done Whitney, duration now, were using and prednisolone therapy,

X, right prednisolone milligram X tapered per weeks on X per X So and of and week for off over it's kilogram minus then weeks. administration now, started roughly at so is weight, day before it's then X body given the day

one simple would shorten sirolimus, a And which running possible patient total XX weeks to obviously, keep at XX, almost see further to at per ideally, it population. even I XX like it's weeks. And XX now as XX then this point duration or of X.X was is for So that for being reduced weeks and weeks, kilogram. as milligrams

obviously, XX roughly. let's right, they mean, and actual have multiple time to from, engagement run I So before the the that study, screening through sure days. XX there's make to within And for to say, days, there's a procedures for patient somewhere can qualify actually a treatment is they in, brought go range a duration trial. say,

trying So but not you I'm exact being a feel. I'm to give just here,

to and and on immunosuppressant come they're at procedure. minus So once X that agents in be screening, for modulatory they day prepped day have given they then they then through qualify the

puncture doing lumbar call here be who is IV necessarily then done can remember, be which the by be physician is puncture, can simple in actually who an that impact inpatient, significant done the because I And simple present X, hypothesis guess, start observe can well could patient, can discharged. protocol doing safety week administer or for over on weeks puncture a at be a can Now to in X But outpatient, as Sean and have by efficacy out is, X, from lumbar caveat a first lumbar the followed and this period we the eventually, a certain week discharge has X a efficacy given an study, the outpatient the before not eventually I is procedure time for week And but very first-in-human a for patient. internist week manner and the we done the neurologist, a setting patient standpoint. pointed measures. drug then X the a it's the earlier we as protocol, generating of and time the and during assessments then the patient as

almost like do these observed and caveat in invasive, a when the to to a it's week. Now then unit other ICV, patients surgical have you surgical up procedures is very sometimes be procedure, a

of kind that's present the picture time. big So the at

those this of a gene being of for the a obviously, therapy it, use, could not of route ease so... palatable disease with simple the administration, the with state much it aggressive immunosuppressive keeping it So regimen, all and broad range too application, make and in more

Sean Nolan

of Yes. XX in from -- And the thing the only XX to just time, just you to talking for is so once I minutes. add itself, would procedure, we're patient administration brought that, have the sense a a the

very as very, can we as it make So like to and and families. their we patients the on short, easy it's

Operator

from Richter comes Goldman Sachs. question from Salveen next The

Salveen Richter

Can be the gains based FDA you on specific of milestones the elaborate and on and/or B REVEAL you'll in feedback you're the Part monitoring? study exact measures functional the looking at objective

Sean Nolan

don't really at that I want this time. point in to of details the Salveen, get into

areas high we've be keep the with it's to function. what we're terms a and tell that better we're all which going I motor function, the milestones that that it specific follow, can gross metrics. level It's to do would been you, we're to very set. actual of the at, and preexisting And and looking going I think got in identified means validated

hesitate another continuing before I'd about We're next with into next as here. up have talked all the nothing aligned. year in there's we in we're we're details locking the good wait and the prefer out them until meeting finally to it of FDA. We've getting coming year. fully fleshed here, first everything half So from in of the but got step. hopefully, end I'd to the fully progress, We've a likely make And until meeting new that the with introducing

Operator

Salveen, may I if check Blum from just have Needham The further question from next you questions? Gil & any comes Co.

Gil Blum

as your D question general it relates to meeting. more a Type Maybe

get you is of new prior helped some follow-up. the through I Zolgensma just from all kind with experience a here, product equivalents So boxes? that the this garnered And synergies checking were the or have there

Sean Nolan

about the clinical talking between process? commercial and then product lot the You're the comparability final from the made

Gil Blum

Yes.

Sean Nolan

make Gil, like the one most X the over high of continue What is I Yes. level, that Zolgensma at brought very, then we between always we Well, product that very I to we dose processes. minimizing upstream. just the that -- experience say we from you're that mean much didn't to would it to to exposure the the giving can. do patients. want similar things do pure really you're we and just a was to wanted the keep They're

looking to from mean, never we from or any I FDA the that, direction than want while above or FDA has at way anything be going been like had keep less generally the And we so. XX% So that. empty capsids

on we focus work. the a did we And where so bit more our little downstream. that's And

that consistent. of so positive improvements the things, were we made data And FDA And with in very, you we potency was the actual of a and very when fashion. the product, the landed look at those. the infectivity And where very kinds clear attributes those we identified and the obviously, were and

planning with and to we're our to at looking look forward make I'd the B final we're the and we and we've use So to we're that. in are we're Part got scale. point forward guess got in process, that that where I We've -- pleased freezer product

at having the a for is path. turns big time on case this CMC So it step And out program critical gets point not generally, because lined for CMC in up that's the us. that the

Gil Blum

the here. is And you very more at consider guys complicated? randomized looking sounds for designs as study -- a patients, in for heterogeneity we're make studies But it that adult still there follow-on pivotal relates Okay. here. or example, very That's like to helpful. natural disease would history it another potential Is

Sean Nolan

all I mean the really heterogeneity stages. they're ages is in and patient

multiple it's reasons group, would come that that optimal are delayed of the of that about issue treatment of be their care the setting to regardless trial an age But ultimately, using patient control designs. we're one patients a a where so own heterogeneous thinking So you if the can construct really the as taking either. dependable up with because that's use isn't

no given we've bring have. around time of I well can clinical effort a final would FDA multiple both case just we've history So to by our we data discussions did said the as -- as And has forward certain very sense. most the say, good why occasions. this. the deal and We've think work great the you the we've to continue basically we assessment of And tell I a with of in the our on had to we'll approach -- open you, pushback. been agency make a understanding makes the challenges think is, been for I can There's that. agency I disease that say and very There inherent would the natural

we're to the of rigor. drug our design us expedited been getting approved in with work that history by discussion. view about the and we've trial helpful certainly FDA, to where encouraged we scientific the look, with endpoints get point possible done this facilitating we're in be that but a that. and And will at thinking to there lot facilitate this where in And so natural combination we've final previous most it's the greatest that's And have in form the thinking time, the the fashion that's allow

Operator

from from The next Raycroft Jefferies. comes Maury question

Maurice Raycroft

progress. the on Congrats

of update of ahead clarifying, first it part that first sounds design have like disclosure? on the be a would registrational 'XX could Just endpoints you your of 'XX.So, half half study that and alignment data

Sean Nolan

world, the update perfect would be simultaneously would fantastic. basically yes. like FDA do We a data and from come the with out to the In feedback

happen that be to final the next goal, our very beginning in of end with to discussion at, pointing to clear We it. of FDA the what And half have would going our next next of in was another year. expect that we first year I just meeting or more preference align year. That's are step discussion. the So, to it's this the

with So here's and to landed tell FDA. the come out you we we'd where guys, love

It's drawn happen. the steps the to here's able Here's hopefully, next and update make we're in the it we've and up, data how that program. execute and

Maurice Raycroft

it. Got

in FDA a patients B? with of helpful. quick cohort younger dose longer-term is on I just based discussed could younger a Wondering you get X part the X the that you you Part And B? in and patients far, olds Part into Okay. this safety so one. at to to Or plans? have if guess, potentially of That's just maybe potential those profile year

Sean Nolan

X ultimately available intent B would for is Yes. adulthood. I throughout -- I that mean, right does now X just patients Part olds. say, we to year would make that to include this diagnosed is our sure Maury, newly And

clinical are FDA we're place, concert of step with it accordingly. we program the contemplating best plan how in or So, in to we'll that cut in that got the our in through We've about and that. and full discussion through and all

Operator

Fargo. Wells The question from next comes Zhu from Yanan

Unknown Analyst

This possible? above with your dosing comparing Can on dose Yanan. is the safety Do data to overall just TSHA-XXX? vector And for on Neurogene you the see higher? to you you then us a there's is it thoughts high give and Jeff think room how secondly, of dose XxXX^XX genomes TSHA-XXX

Sean Nolan

can tox, in mean, non-human Xe^XX. I primate at say I our that we Yes. were clean

could if is choice higher higher something So like certainly it's contemplate. the we the it to. at Xe^XX that on we looks the we go data, could potentially right Based dose. preclinical But wanted

We have the higher. to go ability

So think I point. a that's key

look don't options than how was the X And appropriate one therapy is been Neurogene you benefit Rett and particular just number think time, is derived may think I a I point in benefit is positive to think, Neurogene I available the win, to this is that community hopefully, have that the a MECPX now into that there the that of what better it's data the that's But from get the over elapse. as constructs. And and that time. if at target a details it different families will, Rett. I I say data, think target think there's it's it I relates demonstrating to I utilizing good at, the for we how things to patients. other the think to one, be gene for would community for suffering highlights from

Operator

from Baird. from Allen question comes next The Instructions] [Operator Jack

Jack Allen

progress if broadening to physicians here centers have ask of over which that the with a the high the patients I'm and the made they've X been I about the with on and there's understand the Congratulations we course hands-on been dose. getting to wanted How patients those experience at quarter. about TSHA-XXX. if are additional dosed? dosed should footprint trying think

Sean Nolan

-- sites Yes, sure the X now get Suku X available, sites right. But protocols. this we X right available make don't total have in to dose I

patients And different high that so, dosed X of least the dose, were at the it's at sites. X

both So look total, makes And, right sites. a dosed now, programs, hopefully, when patients. that that the -- REVEAL we've least at X X -- at had sites have you the sense, different there's total

Jack Allen

Got then across is clarify, dose think X guess, to sites, I way the high just both And about the low it. it? the and to

Sean Nolan

Yes.

Operator

from from comes Joon next Lee Securities. The question Truist

Joon Lee

for your of updates be are you part we first A? B, assessment? that Part tracking As of Part already or RSBQ longer at if will sharing look that's can as And endpoint forward data you Part half A something for share in least you RSBQ to next year, you you're providing are the in on no considering

Sean Nolan

being given very FDA. And our it's primary -- with the with primary option are we're that board secondary matter. that it to gains reasons, are discussions going completely not we that's are no on think for and focused and the us importantly to fact endpoint RSPQ and that something demonstrated. didn't see at. we're those give again, anymore, on to a the still see not We the on so, what view functional for show Joon, more as is it. Yes, look updates a discussions a endpoint relevant We a our to continue with most FDA, CGI-I or are really Yes. in endpoint But that that's that. in as they clinical value viable clear observations to

have perspective. has makes be So of consistently program effectiveness. trying the given other We're on not that it's ruled have. effect that out from good we completely forward given going updates program just give on on that the we it's no RSBQ, been that sense. assessment to aspects clinical and people the very of the regulatory focus But put clear will we a it a it no And felt

over into the of about the about As we've collecting terms hand it A, motor to that already will mean, several we're question I Part having We've time. well endpoints. function with as reported that your of are milestone That we as that the course milestones gross on function. and of in relates lot go certainly yes, data discussion discussions a FDA had

we're So, give that we And the in excited. we're we've be like? our update everyone for year, hopeful and can trial data then in comprehensive we do half terms first in endpoints, Part next landed high-dose it to of how look very when of what A? what your where correlate So, does design seen from

the with great with in good of regulators have a generate a execute us think of to And position to our dialogue across as team I plan in share we exiting ton a put momentum. that we're in and the clinical continue a do what year place. the is board, we XXXX. first half to We're data

Operator

Tuerkcan comes question Silvan The JMP. from Citizens next from

Silvan Tuerkcan

on the Neurogene equivalency and view that between recently just exposure about of to ESGCT I doses want also dosing ask and at biodistribution. data your presented how you you've the given

Sean Nolan

Silvan, make the kind and it can be question? giving you want understand to of can accurate answer. in I sure I restate that

Silvan Tuerkcan

the Neurogene at little below dose the you now is bit administering, approximately Basically, low what administration is route and Obviously, higher the escalated a differently. like dose. of to same your is dose

of X just means seen of efficacy part I around terms therapies of have X the for an critical brain any exposure and get the gene what So we've the what with far of wanted idea the -- in you the the to sense if products? that so is

Sean Nolan

I one, think, versus number what's ESGTC that to you to look context when this direct hopefully question intrathecally. bioavailability out go we good the like the and I But Suku brain giving of the can Well, tackle at data together. was reported

the or looked primates direct we XX brain. biodistribution AAVX had transduction what to programs that And happens at so we there between non-human a levels data, we over difference ICM when with had. And the all of versus across wasn't intrathecal really

we first is that biodistribution So, data the makes And equal. when I initially, across clinical at two, when to because reported clinical the domains. think the appears data, we seeing you point look were effects our occur number sense be

all you and And fine gross motor autonomic know, different the function, so communication, as socialization, brain, function, parts sleep. happen seizures, those in of

getting look you later when that you data this all lines to that talked data X with CGI-I. to improvements similar that have to the week, I in was be biodistribution point about up well the parts. And there at seems So, effects, X then that to announced be

delivering routes So less that point effect than can used clinical what XX% to administration at And be also it the I of that equal in of is looks like about our relatively would terms the the dose was the just Xe^XX. are construct fact of across And design. domains. part

single levels double so we've having using than talked greater about And that strand. the fact a versus a transduction to strand of and generally self-complementary efficiency leads

couple saying years. of been up for with kind line of data the all what we've think last the I So

what encouraged breathing, at by gross points. were the across seizure we're as so, X activity. seeing effects And little sleep, we dose, fine even to in And pediatrics motor skills, at we X Within motor impacts we've was XX low weeks, on time were weeks. in seen early the skills, that seeing as

perspective, over time. exciting, are and to that our we patients from trajectory that's super how going for do So, think sets these the

see as gains emerge of that course dose, hopefully magnitude the and as we well. at that over the time, even at and over So, data low data time and our we see dose, sustained a new longer-term believe strengthen anticipation better high the the we it's unfolds

Sukumar Nagendran

been ICV approach appears, both Sean, I has both of -- add approach, the concept now the it that also the right, and proven. proof would intrathecal

Neurogene dose. is, the can So of that it's is certain the known a higher Number impact overall does safety And the gene two use dose, in types from an only therapy, from the even standpoint, sometimes standard, signals. one. changes is pretty well number yes, small higher thing safety algorithmic an

a safety recent on. going is to I as the issue, of with lot think what obviously, there's So curiosity

with we biodistribution, if we've shown and or quicker activate a effectively standard quite was of may a questions if construct, puncture, a you primates the you The rapidly What pointed network use will That the comes takes construct. is quite to biodistribution take clear. And out, your than neutral while, lumber you around, when much right amount pretty is single persist. is via we work lot very slow, equivalent from it it equal even that get biodistribution, go to same nonhuman clinical as efficacy, ICV? have a now not then did the dosage of and we it stranded single third a the -- intrathecal don't there efficacy a ICM you cohort of large

constructs are those questions, some X I be think, have the to the answered that time. So between over of

Operator

comes question Tapper Capital Keith BMO next The from Markets. from

Keith R. Tapper

the execution the Appreciate across program.

trying exploratory higher frame for durability, necessary Are or dose the dose? could to expectations population higher with the safety for from patient remind for then I in of a we where And doses patients. mature the moving efficacy, upside given we potential X you really motivation broadening characterize for guess, experimental, are us data low-dose the Just Maybe investors to looking cohort possibly you as competitiveness? approval? of or the could today, biodistribution trade-off the of for pediatric high-dose and an absence to

Sean Nolan

more we the the to should Yes. in all go there decided preclinical based when -- benefit be that I of out encouraged assuming doses, risk. have you work importantly, the the put benefit utilizing the we've target equal our the biodistribution, approach, biodistribution. Intrathecal is, the to not and feel think the studies, that in we -- in to we the data have and the that Xx benefit/risk. preclinically, safest, tox picked the support therapy to Keith, Xe^XX clinically intrathecal that double And margin we fact we given all about to preclinical that that, mean, view, safety done. data And in ways that if on one minimize see I administer safest we've the our that

-- view safety our that very is is incremental any that we're high low going better with type than very going a likelihood by that seen we're there see chance And we've and derived a benefit it's the at what a low there get dose, to going of relatively So, issue. at patients to dose. good there are the that is of pleased dose to the

no So, dose. function, to the the high the a that IDMC liver all you, go to we've parameters very low of dose, stuff. And to in And us, show that versus continue of high calculus meetings, it's are seen kind we tell for the X. I easy difference in platelets, looking at essentially let's it's can say, collected, whether all different

even decided we were that about protocol. things on and why IDMC recommendation. move And than high to that's again, the have to, earlier course, good the of the dose So, feel based we supposed supported

Keith R. Tapper

Okay. I could. Great. helpful. That's if follow-up, one And just

considering how disease context Just, that we should the clinical data the adults. we have in terms stage original mature development and about adult of baseline goals more and trial Just maybe adult think of differences in cohort? for the then of characteristics to and the translatability pediatric brain in the

different do way, versus pediatric to you expectations for responses have adult Another treatment?

Sean Nolan

of Well, what I within X felt, see was within adult normalized. think started efficacy. any actually kind wouldn't was when I weeks, view keep the -- That the we and we the X in think sleep trial, consensus community KOL mind,

Sukumar Nagendran

X days.

Sean Nolan

time. the right? And happening the over adults, functional scale was time, function And the motor course milestones sometimes what's in we will strengthen gross do the might those patient, in the X X years activities like data over Seizure when patients same. -- that's course hadn't okay, sometimes at living, reduction, being the of days X are or the gains, achieved X the high to what over the we've that the weeks, over get essentially. better of improving seen within it time. daily days. that so of occurred sometimes improving And But stay dose to CGI-I, the seem improving is look

benefits, the in that you described and improvements are adult get over it or early way And early gain. we've time, is either those population, functional clinical so, And they the sustained then see better.

that pattern. expectation that It be the so, And follow our also the a should group case. it's pediatric similar in should

That's that At June. out with weeks, the And data so X we in put X-point a improvement in with we were we had encouraged a patient CGI-I. early fantastic. very

had XX% And a improvement. years. function, X in thumb point after X the right? got not having incredible. seeing had girls one grasp to so, of Like improvement, had And XX% for of her that's her use terms the patients mean, pincer I and of point were a changes it X ability occur then we back

patients of better And the those get over that course should our so, time. view it's

even course As they expect few the that get having the same. adults data stronger, early better the the to would pediatrics certain we've in to they and a got do of The get of with seen aspect in what the used socialization over skills. months, also we

-- in like that So, possibilities feel think you it's pretty short long and on I've the both dose what the seen looks the better, about I even even hope patients looks long kind X low would of about I'm hoping the than I that then good low-dose with pediatric the high over adults is and based term term dose. better the the pediatric the data and in

worked those with so with data now I got at we've X a to So, getting online not multiple XXXX, why mean, scheduled got X and X sites it's about us dosing that already. because to with coming our -- from site. think well We've regulators we that the enrolling are X team the the has active we're hard just getting one opening sites. online, they're other position we're again, here excited put dosed in of I and that's patients just

is and game going we to to look program where So, the be are we continuing feel good played. forward the we and about where

Operator

much. Nolan reached to the Thank call end very we you session. you, closing Ladies the I'd question-and-answer Thank to back the have like Sean for now and And Mr. hand sir. gentlemen, remarks. of

Sean Nolan

I up night. evening and just to the look follow update questions. Take this to and forward everyone hear want care to taking thank for any a time good have the

Operator

conclude Thank very and that today's us. for conference. Ladies joining gentlemen, does you. Thank much you

lines. your You may disconnect now

Taysha Gene Therapies (TSHA) 13 Nov 242024 Q3 Earnings call transcript