TSHA - Earnings call 3 2023 | Taysha Gene Therapies, Inc.

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Operator

Good afternoon, and welcome to the Taysha Gene Therapies Third Quarter 2023 Earnings Call. [Operator Instructions] A question-and-answer session will follow the formal presentation. [Operator Instructions]Please note that this call is being recorded.I'd now like to turn the call over to Hayleigh Collins, the Director, Head of Corporate Communications and Investor Relations. Thank you, and you may proceed,Â Hayleigh.

Hayleigh Collins

Thank you. to conference quarter call. welcome and financial and update corporate afternoon, Taysha's XXXX third results Good Earlier results quarterÂ XXXX. for a the today,Â TayshaÂ issued press third release announcing financial A Head call are on Nolan, Taysha's Financial is throughÂ our press Officer. Nagendran, filings.Joining and Sean copy President Kamran Suku website Chief and SEC today's company's R&D; and available on me CEO; of this of the release Alam,

quality including or statements, note including a our reproducibility preclinical question-and-answer also research, candidates plans favorable statements in relating candidates. treat TSHA-XXX, conduct well be actual candidates session forward-looking results, include stated that remarks.Please from as also ability of may to the cause and seek product patients of may This on upon of property risks dosed our development and our in our parties for for timing for opportunity and those to and requirements life discovery hold the imposed obtain ofÂ and our differ prepared of facts substantial results will of today's implied for operating may the matters forecastedÂ cash our the activities. discoveries, and to initially or risks statements. the of contain and protection in programs. the our and other These research positively will limitations results or to timing and and other by materially by therapeutic We making strategic product not future intellectual and and product dependence the product historical plans for call to our second forward-looking regulatory in course strategic our product Various and we forward-looking statements growth, clinical relating development statements to potential regulatory that impact candidates, and in trials Taysha's and our any and patients we controlled disease Taysha's results call, third-party REVEAL interactions expected clinical funding following relationships, patentsÂ owned the clinical third to such seen those runway and information. first related patent trials durability uncertainties commercial include candidates, market These results alliances, are of the regulatory alliances our development to including trial as and of

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

Sean Nolan

in Chief will an will I Thank corporate on on of remarks corporate Alam, engaging will regulatory and Canada up our planned will for and to questions.This Nagendran, Rett clinical Hayleigh, therapy and discussions the follow update up activities. quarter, generating we clinical syndrome, further of Kingdom. Head conference I and and Kamran development program Taysha Dr. clinical development including update, clinical in financial in Suku advance trial States the data our with open financial to on in Financial update program. adult our continued our you, lead of provide United welcome, results call trials brief of a and provide President quarter R&D and third and the pediatric a Officer, with United XXXX closing our the update our new everyone, gene Then our begin Today, TSHA-XXX in call.

when syndrome. Rett efficacy Phase As for expectation focus advanced it the the the the Therefore, trial safety. designed assessment, and in adult the new relentless manifestation and areas, trial a progression was when exciting have improvements we is has efficacy in on the the XX low treated.Today, syndrome patient week community. to which Canada, one reminder, study stage the the initial to primarily a domains several the sustained REVEAL REVEAL among KOLs of first across safety. we Due is disease, was multiple TSHA-XXX hand X/X a very evaluate in are impact first-in-human that adult Rett of X to patients that demonstrated a hallmark clinical to there was initiated encouraging Recall response population pleased and that in share of we measures as announced primarily key adult placed function, of was the appeared including

treatment-emergent between XX different adult the Principal of efficacy observed of and treated sustained sustained across the early of initial first at demonstrated baseline REVEAL to of socialization, patient's and provided of demonstrated remain ahead, XX-day Phase patient manifesting therapeutic one believe focused with autonomic X/X from skills following walk period on recommended Rett data, potential syndrome Suku following the genetic demonstrated adult cohort, review our mutation further across construct. could Investigator while by the showedÂ TSHA-XXXÂ was initial mutations of as the validate and patients adult continuation very are data as week to to both in further clinical in data fine profile in presented weeks of clinical across severe patients disease also second first a TSHA-XXX in patient The X multiple weeks will convened are prompting, safety the positive data from we and addition with improvements initial as in geographies. first outcomes improvements TSHA-XXX. dose initial patient trial Interestingly, the the the weeks patient discuss from low the the similarly X encouraged clinical function, more patient and response treatment. The detail.In coupled the patients non-ambulatory, consistent and treatment.The the domains more the and patient. treatment. and the exploring early the patient third key first motor genotypes than domains, clinical of clinical observations domains X improvements the X clinical responseÂ through the ages we data second dose The a have different MECPX well X We tolerated Independent no with Data support with data, patient patient's including assessment. well XX-week events XX-week required characteristics example, completely as the phenotype clearance measures adverse of data assessment. the and initial serious across first was improvements events mutation. different Committee, the adverse encouraging these that X-week showed IDMC, two gross in improvement and an TSHA-XXX.Looking second new Monitoring number a related IDMC as withÂ TSHA-XXXÂ following the clinical recently Additionally, XX evaluating dosed multiple second the patients, Based thatÂ TSHA-XXXÂ was the patient TSHA-XXX both with a tolerated across with following weeks in for first patient the quite the assessments early both well no as the transformational patients, from or and evaluation potential serious clinical on And patient's treatment-emergent patient second in the

remains low-dose in XXXX third dosing or of either the of in U.S. the quarter first the XXXX. theÂ TSHA-XXXÂ into and track trial on dosing pediatric earlier in with first XXXX. the stages dose Expansion to in the cohort our anticipated the of of fourth patient expect the patient We of planned of quarter first complete adult quarter disease

with our end response that Rett recently this with MHRA receive for Additionally, a we the TSHA-XXX to patients the by from syndrome includes trial entered no application U.K. agreement of security and expect in Trinity submission a Silicon on existing loan pediatric into Kamran will or clinical cash covenants will by year.We Bank. into our X security details of XXXX, and quarter agreement more and This TSHA-XXX. our runway which agreement. Valley extended the terminated development has with financial provide warrants clinical further loan on the Capital support

our the With data to we of encouraging milestones. in clinical value-creating believe extension key are our TSHA-XXX, we across execute runway well-positioned and

program in will provide a in-depth plan we an to to syndrome. effort devastating forward, to patients Suku? more this with call bring over potentially now transformational our program to in to discussion on turn clinical the a Moving to TSHA-XXX living advance treatment disease.I Suku Rett continue

Sukumar Nagendran

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

reminder,Â TSHA-XXXÂ utilizes prespecified All ongoing due Rett collected a efficacy a miRARE to in of MECPX designed provide what therapeutic Phase novel benefit.TSHA-XXX small address a mediate the but on currently central Phase are that syndrome X/X miRARE either and Rett expression with of to adult trial, REVEAL first-in-human normally. syndrome MECPX in investigated mitigate mixture randomized our trial, this designed measuring of makesÂ Rett deficient in The which a As this technology novel results mutation. nervous the X/X safety cells syndromeÂ challenging data also approaches, and overexpression. open-label dose-expansion as primarily to silencing ofÂ TSHA-XXXÂ inÂ adult hypothesis-generating. appropriately randomly risk expression measures. or The dose-escalation and that is basis we X-chromosomal molecule is trial cell-by-cell can MECPX MECPX efficacy therapy simple loss-of-function traditional efficacy gene a being is and in system expression a preliminary the challenge inactivation evaluating The occurs was technology with study safety and in is in study with heterogeneity express MECPX females being believe

endpoint TSHA-XXX these the dosed continue data thinking across cohort primary cohorts, to adult the further registrational purposes. study relative more To with have our for first date, X we generate patients lowÂ dose. and been to optimal measures longer-term As patients will evaluating selection in inform

XX-week encouraged the first transformational highly the reviewed of we IDMC potential for safety are events X-week the in and second both reinforce We the patient assessment of serious seen data, patients.Importantly, generally assessment adult early data tolerated the by by post-treatment and adverse well these treatment-emergent for TSHA-XXX.Â TSHA-XXXÂ was have as no patient. which efficacy the with been believe

data, progressive not severity efficacy nature referenced due important did stage of syndrome, the earlier, to terms particularly patients the it adults with Sean to Rett in understand with that as disease meaningful In is and of syndrome. we expect see in to of efficacy Rett most advanced data

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a partial missense the across baseline, to and baseline in patient, clinician's who contrast, mutation have relative the At a CGIS, fine and frequent participants support, the history large in lost indicating is she manifests function However, the in clinical with manifests a limited mutations patient presentation clinical dysfunction, MECPX which her disease, seizures. scale of mostly ability constant Prior reflected at held She bradykinesia weak. types in hypertonia Clinical phenotype. that gross phenotype. gait a scores in is a phenotypes that reach of The apnea in her function severely MECPX deletion of reliable stand early and have mutation is participants' or of scoliosis. milder by Impressionâ€“SeverityÂ or to one, and childhood. but XX-year-old including Her X-point sit baseline. severity CGI of old.Additionally, episodes the a motor level illness ambulation constant experience patient reflected was her kyphosis her diagnosis. only the was movement, function of at that ambulation, severe correlating Hand severity more she treatment, essentially objects presented patient's had patients with was She with ambulation score disease measures, Rett of higher that hand. Studies prevalence the dramatically state mutation female a of and her which possess old, milder highly a very patient presentation rates is firmly confirmed with and motor baseline.Prior a of within She in different severe by The back in which to progressive severity hyperventilation and to The stereotypies and prompting, lost clinical ill. together. predictor had grasp with body with different of herÂ MECPXÂ gene had and a her walk XX-year-old had gene, could a Global and manifest as she genetic severity syndrome required treatment, Patient and the hand loss a gene severity. evident ability X wheelchair-bound. form efficacy XÂ years MECPX the our had X complete is of and same appeared impacting experienced and has backgrounds type loss balance. greater female, In a has was loss their experienced to second no little patient's years she non-dominant had hands to

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multiple impacting domains Importantly, and we patients measures across consistent fine of improvement clinical and withÂ TSHA-XXX. are across following in both seeing in following activities Investigator, genetic pattern both motor demonstrated the despite treatment TSHA-XXX status differences autonomic of domains with key efficacy including the gross on severity.Based treatment improvements clinical patients function, Principal and a socialization, living, daily clinical and the by observations skills adult

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hyperventilation.The patient improved and a holding socialization demonstrated and breathing function and improved autonomic both also social reduced increased XX. dysrhythmias, efficacy measures demonstrated treatment, in and breathing also breath interest measures patterns including infrequent on improvement Principal improved quality now in update Following first sustained patients both spells with with less reinforced activities duration from patients these the and which across with Investigator.Let's the first with at begin patient. the improvements TSHA-XXX, demonstrated sleep week Overall, treatment clinical observations key following an efficacy communication by

XX. first improvement measures patient new key efficacy The through demonstrated week sustained and across

Impression accounts SyndromeÂ that of score score Questionnaire, the indicating X disease. assessment assessment Clinical toÂ Rett much clinician-reported sustained improved Rett or Syndrome CGI week XX, the at RSBQ. the improvement of had X-week initial sustained overall at is with key adapted improvement Global CGI-I, she Global Specifically, Clinical consistent in X treatment was assessment. X-point week Behaviour a from Impressionâ€“Severity the CGIS, or or for of Improvement is reported following aspects A reported which and

sustained that syndrome baseline week the improvement demonstrated XX. patient XX consistent ill indicating Rett the at is score score.In behaviors, severe hand is improvements CGIS X, behaviors, which of questionnaire demonstrated The score ill week from a markedly XX nighttime in a a XX-point expressions. score a score XX-item score with X assesses of XX, at score X from characteristics, total patient and the the indicating at by point Additionally, breathing driven sustained baseline to was problems, of week to X improvement of RSBQ, a the facial which

following R-MBA, from a Function of Revised skills. social improvements Rett The in by X-week RSHFS. of X Motor from motor XX the R-MBA, XX.The is the therapist by X-point to that Hand RSHFS hand with of a The levels, of first grasping outcome of in was any Assessment demonstrated demonstrated be score an and can the that a grasping. evaluated assessment clinician-reported Behavior a initial baseline each scale. question syndrome Rett which ranging A Rett much X score experienced, score Syndrome no from function video codes of week score Importantly, reported a or is points week patients XX was X at indicating of and or assessment Impressionsâ€“Improvement independent dysfunction a objects which in improved Parental improvement clinician-reported highest caregiver-reported of who The independent at demonstrated uses Scale, XX. PGI-I active patient X. function the also to hand in new overall PGI-I XX scale treatment score at improvements is measuring improvement is score driven disease X is total behaviors the achieved physical a syndrome, of of Global

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RSBQ's As patient's comparison, XX. week was the score a first XX total at

The and second facial patient's score was walking, in abnormalities. standing, driven breathing rocking, expressions, by body improvements

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improved And in the Investigator more the Principal X. at relaxed the patient are since and regression for time with forceful measured noted stereotypies, age displayed hand hands. first less not the which However, RSHFS hand wringing open

the the the our SEC. can September filed We XX-Q quarter patient's the time. details will available ended on continue monitor in be progress More with to over data XX, for XXXX, found Form

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the we REVEAL available the ahead, to cohort updates the dose clinical XXXX. of low-dose X/X in adult expect the patient XXXX first provide further or quarter fourth the in Phase the in to of trial intend cohort XXXX. either complete Looking We dosing quarter and of third in low-dose data adult first from quarter on

Our effort to to expand pediatric of early the patients disease evaluation remains with clinical progression underway. stages

and IDMC in the age age. evaluate part B of study year of to We TSHA-XXX to clinical with hierarchy and and activities cohort will focus pediatric by first will dose-finding are identifying quarter cohorts, cohort on pediatric focused the Part Data dosing from syndrome trial of age and study delayed Rett initiation dose U.S. X tolerated and anticipate agencies or randomization endpoints trial for pediatric XXXX.As X of X and treatment final will Phase our a elements the Rett regulatory of X X part on in randomized a of B a the cohort years assessed administered or syndrome. X X study, to key A X girls for X A maximum maximum determine patient to of with dose treat of duration. expandedÂ X in as the first efficacy the part to age be such years reminder, to cohort

Commission treat MECPX there root XX,XXX program patients by a syndrome encouraged in of of end that of receive Fast this has U.K.As year, the FDA from designation the the from associated has designation U.K. from Kamran on syndrome. pediatric drug syndrome. further disease treatment and and our a between of to and need caused Overall, MHRA care We progress.I already There the received drug inform orphan early unmet turn -- been XX,XXX results. will reminder, forward proposed the expect are which is over the in no submitted our orphan U.S. X discuss high to available European the Rett application additional mutation are and clinical it. will the the timelines for study cause Designation EU, and we financial efficacy with Track in U.K. afflicting and highly to approved safety therapies received currently rare and by Rett Kamran? disease-modifying feedback pediatric U.S., TSHA-XXX Rett trial pathogenic the patients recently granted now by call data adult for first with look likely the sharing to genetic burden a pathogenic high the and

Kamran Alam

Suku. and share, $XXX.X warrants expense due decrease September pediatric private you, was to a headcount expenses Thank due consulting for ended million September compensation with efforts offset $X.X in reduced raw the expenses of This $XX.X or in to REVEAL material reduced August due X and recorded ended pre-funded XXXX. or from XXXX, to private batches due purchases. Rett $X million warrant months fees due partially administrative and QX with liability headcount, issued was XXXX, trial the were a a of ended of expense net fees, expense to from September and ongoing financing million, September the in clinical to liability-classified was for million completed and as compared fewer loss partially net connection for value result months XXXX. allocated fair per ended September $X.X was by XX, the XXXX General to lower $XXX.X change $X.XX development XX, a by of XX, of $XX.X connection ended the X months months in warrants $X.XX loss adult million million months million, issuance syndrome studies. a for million were Research and compared XX, lower million offset $XX.X $X.X of the XX, Net in to costs X financing lower and per XXXX, ended reduced X XXXX. in X the placement milestone increase $X.X September million million completed the million, XXXX.The to in X due for activity share, pre-funded of $X.X XXXX, surrounding professional the XX, fewer the compared for months The a million decrease placement non-cash August to change $X.X manufacturing $X.X compensation as the licensing

the of Silicon and cash Valley that capital into cash into entered XXXX.Taysha and operating company will its and terminated and a cash requirements existing expects Capital its Trinity agreement fund loan $XXX.X on equivalents and with XX XX, security agreement XXXX, security Bank. November As cash September existing expenses had million. and loan equivalents The with of company

this there or cash and result runway back our remarks.Â Sean? warrants securityÂ agreement.I the with now his now into Sean for As the are Sean to associated noted, no of loanÂ and agreement, closing extends turn call as financial XXXX over a will covenants

Sean Nolan

Kamran. you, Thank

to REVEAL adult XXXX, clinical our footprint additional U.S. and Rett as the patients families high-dose and begin our We data key and different through week Q&A milestones are in operator validates in upcoming TSHA-XXX will both improvement in profile genetic and our the and severity, ofÂ TSHA-XXXÂ for ask the now with clinical remain on patients safety initial to including potential very the mutation of consistent trial dosing syndrome. in presented XX with cohorts data We believe that, and into by observed pattern living adult We date. the response across observed program session. U.K.With patient therapeutic highly the for low- expanding domains with clinical The of the I our focused today patients sustained patients encouraged early TSHA-XXX both first we is Operator? in coupled approach pediatric encouraging. the further the

Operator

Instructions] this from be first At conducting we session. Canaccord you. [Operator question will a Whitney time, comes Thank from Genuity. The Ijem question-and-answer

Whitney Ijem

Congrats on another update. good

me, for great again, First question data.

from of the to it the patient, Just increased week curious, in X RSBQ, XX. slightly terms it week looked in first like though,

Sorry I that over on changed can any provide if domains, guess, frame? which missed it, particular, you in more I but color, time

Sean Nolan

Whitney, -- I but can Suku, and think change fine Would Suku? domains to turn it the main anything there in I socialization and you were to gross is over skills. that motor there breathing, add that, would where were you

Sukumar Nagendran

the that obvious the note well evaluated were domains that evaluated to observations Sean. when think I application And that been comes as mean, some with No, CGI PI as that correlates those have out, you is I to it what and improved. the of interesting of by as pointed CGI-S. is broad it are clinical also the actually

an weeks one that is you sicker the see was the from there treatment. X, weeks significant to that patient patient correlation it's post XX interesting maintained in much So and also X given RSBQ than change

Whitney Ijem

And then --

Sean Nolan

help? that Does

Whitney Ijem

That of then derisked? broader for guys does,Â yes. just where else proof-of-concept or in would perspective of or to terms you patients you guess about kind or a these be And thinking a kind this of what what it kind are you I patients, consider remind looking sense? how else tech? might data additional about technology of can the X patient number, And follow-up question. miRARE us indications you're for from How make thinking

Sean Nolan

CGI-S right? Sure. comments. disease say has Well, and first if Suku I'll I the miRARE he what's additional But go was technology first baseline, X. to the to proof open I concept the that mean up at had severe us about would certainly at significantly is encouraging of patient with

from that clinical domains. encouraging And XX, -- that would infer low preliminarily, MECPX. through of you week we're response yet patient she's relatively that seeing juxtapose across then endogenous level with And a with you got two. So

So of genetically. significant based phenotype deletion one a much mutation, disease. a keep on in patient from missense is Patient a less severe resulting that in the had two mind manifestation

more let's that yet, any we, And probably So endogenous you week one. say, week, would than is generating MECPX through concerns safety patient. patient seen haven't think with particular X, she

seeing genotypes, seen, and patients very first good you're say are safety X with the MECPX. be patients profile.So corresponding the way, miRARE there I these and a safety seeing appears clinical of response across in think to would of consistent I you're domains, indicators levels a promising of potential different Whitney, So first endogenous X And very, the phenotypes, technology.

Sukumar Nagendran

is gene presentations the that population what is piece as whole.And And would is I with classic see to that or different worked to therapy out quite given Rett patient give present will you very as you be miRARE different by quickly our in genotypes PI the Yes. enables of as us terms a patients. self-complementary you you that and asked, the protein us Rett as X the very that they Rett And noted puzzle is It will measure that to in different positive second pointed to more that syndrome improvements, actually happen such simple weeks what given appear it were which improvements MECPX have reassuring accumulate there technology product technology because just clinical other we broader continue our what much that fit post to I need And And X products as accumulate a applicable maintain into add see act. precede changes effectively gene syndrome, think very control need that both a said, of is to classic the sometimes response, of also take the for nucleus. well, to tight genotypes Sean, to the critical this in data is, classification therapy, also has levels it therapy because confidence phenotypic syndrome. in which as to clinical reassuring the to longer biomarkers dosing. on in X the been based gene manner within also this the post

Operator

those are questions? Whitney, all your

Whitney Ijem

that Yes, does.

Operator

next The from Fitzgerald. Cantor comes Kluska from Kristen question

Kristen Kluska

readout, sudden my And With if also a the this I exceeded you patient me Let wanted add see here. respiratory of expectations some congratulations commented second items. cardiac the lot the this to about these a particular about kind a experience can understanding measures and you with the that do complications from these death importance a of of result of give disorder, from our context as of of us matters. a about patients the X/X some

Sean Nolan

Suku? take, to want You

Sukumar Nagendran

a me important very address because question. let that's that Yes,

do And episodes you patients breath respiratory one. have followed dysfunction. by of So when That's it's hyperventilation. they have where Rett of think abnormalities, syndrome apnea autonomic autonomic holding significant dysfunction, usually they have spells i.e., typically

stay of have seizures, significant have may And diarrhea. abnormalities I have history think dysfunction. fociÂ exists. GI fall also a times sleep cannot terrors. have they Usually, they the also Second, sleep brain they where at than the asleep, depending part asleep, which on They also cannot of it's more constipation

week are patients.And a it these positive respiratory patient significant have abnormalities. once Rett we in and on syndrome within one impact standard what comes these or gene two that So when patient our X pretty to dosed, therapy is highlighted

did was We about patients episodes. in as cardiac in reduction EKGs abnormalities these abnormalities apnea hyperventilation So talk significant the spells not well done. rhythm because a really on cardiac these there any or have did as not any concerns

not this clinical our in an are those measure therapy. efficacy for clinically time So gene evaluation with at appropriate point for

Kristen Kluska

guess shared differently that of scale phenotypes types focus the or specific at think weigh think across different for particularly do X any more picture? So bigger more are here, you important, I different are shared. of the on the is anecdote looking I'm then the of it shared endpoints And you I of the trying just today important you phenotypes the if to different the is ask guess weighing all question to while these each them

Sukumar Nagendran

me for clinical present are another they're autonomic take function CGI-I, question Yes, what one have at of two, let and would RSBQ, you the the of difficulties the objects patients, in their our challenges. the gene question. one them then even they significant These you if and we Rett of break what at because sit, dysfunction interaction with that focus them different, into very difficulty abnormities sometimes age that really looked therapy impact the and social cognitive after meaning when clinical movements, also was with I that patient of of is had posture to, I syndrome function abnormalities That's and patient them look also because, to the tracking abnormalities abnormalities have you with, XX. probably important to and present hand appropriate scales. have though in CGI-S, eyes.Most example, scales referred X. R-MBA, milestone with stereotypic on their they they difficulties their have do walking have gait patients developmental X have maintenance or hand of an with patient and and phenotypes many both are Patient think, age unable after down two

that higher milder components And severe phenotype, that and you the in gene depend that of you the in phenotype. the and will on of So disease. on, more impact the patient, actually focus change and dysfunction the scales how that to see some scales of numbers the post-treatment, clinically, one to, overall a if are highlighted the the much we aspects on for see a is both have then patient the therapy phenotype really in patient degree can those our then did the and severe on the the also we did and therapeutic second RSBQ then relative the two on have these lower efficacious, change are the because much refer We've number.And the be. these scores The numbers impact autonomic scales is. even has you'll RSBQ, on R-MBA the highlight

leave think, far aspect relative the management it And you clinical product a So that review from impact, the have mind than to important keep and at standpoint and scales. regulatory certain more I'll because I broader look clinical sometimes in clinical is transformative at impact for of now. that

Operator

Goldman Salveen from The comes question Richter Sachs. from next

Elizabeth Webster

was activity could seizure for seizure Congratulations I on you the additional diary. data. hoping the This the provide Salveen. in on is Elizabeth on color

the what's now? for treatment? rate how observed Specifically, prior know patient each also after And second what observed for you first on some provide the for seizure to quickly were patient, then could was if color the being baseline were observed? And soon steroid improvements treatment. those quite patient, I

color So would there any helpful. be

Sukumar Nagendran

Yes.

so very clinical to seizure both you patients. a history in the that's walk aspects because -- first to you and So that of patient are through try important question and I'm there because second asked going patient lots

therapy quarter had X X, to with per one syndrome, gene given. seizures the stage X So a XX-year-old female, patient was right, before Rett

week patient The works this dilating After on the reported actually were PXXX the dropping in was which the the there the results prednisolone sirolimus reviewed by is system, was sirolimus. therapy, first X, inhibits X seizure on PI. and and no nor post-gene significantly. in weeks is liver diary levels seizures noticed EEG that cytochrome And in what

what post-treatment. this I very patient.From XX, So X seizures had seizures X X in what therefore, And some following about recall, breakthrough week dilating now that dropped happened there the think levels I to during is the this is which period weeks were to the up patient after low. below

is dilating the given, was were seizures, had therapy but to gene usually Now levels the think was patient XXX, before one this also it below note, when of interest XX. usually, above it whenever I

patient allowed but the that levelsÂ were seizures, I gene -- below low levels dilating think had got though this which happened say I effect, way seizures. for breakthrough even gene X weeks too therapy still when theÂ dilating had a And the breakthrough therefore, this post to protective therapy, So would XX.

So the that is patient patient one well. doing and is

Sean Nolan

would just to on XX, post-treatment week that through to comparable. I so Elizabeth, try punchline and hit seizure rates the are -- pre- a handedness say, question, Patient

Sukumar Nagendran

Yes.

Sean Nolan

below generally experience And looking when like In patient XXX. now had less XX. occur that she's levels dilating seizures than thisÂ pre-treatment, she is it's if the what the seizures post-treatment

So at much a lower ofÂ dilating. amount

Sukumar Nagendran

then you, Sean, which quarter. patient for per seizures had XX is X Thank every that. And month, clarifying guess, two roughly seizures, Yes. I

recall, I But breakthrough treatment seizure gene up therapy this was XX. it. week patient Following to one day with X, that had product, our if on

Just seizure. one

patient So is this incidence impact that well. is a seizure in an most likely gene good that having on as therapy signal our

seizure the you. question for that's So the on update

Elizabeth Webster

on of of the rapidity second the patient. second then just question in the observed response And

Sukumar Nagendran

Yes.

So important question. that's another

again, the So back go to product DNA. technology, our a self-complementary to has just

the starts producing system, once within the clinical XX Investigator impact noted includes Principal X nervous of reducing central the being given into appears abnormalities. as puncture. CSF to And impact well that the protein. we noted has via and So motor think be formed function post it's the some episome it initially this within given to and XX days on some therapy the lumbar autonomic hours as gene MECPX the -- central And is gets into

these see because we of to hope some symptomology. relief that give that will their So serious will continue and hopefully rapid that, we of patients pleased are

Elizabeth Webster

again. Congrats

Operator

Co. The next question comes from from Needham Gil Blum &

Gil Blum

impressive. Allow me actually congratulations. to pass my It's rather

some about but scale, familiar ceiling with do want I is about leveling thing possibility? I'm we're be these a could seeing XX. metrics, of to mean around not talking understand that super one the So of there specifically a RSBQ, effect? I a kind

Sean Nolan

effect. ceiling A

Sukumar Nagendran

Sorry. Go Sean. ahead,

Sean Nolan

there and at or I to being particular what think we're study, to stage have we the a ceiling non-clinician to be disease, the be, the would time this Gil, dose the all that, have Well, into a whether in in is of account point demonstrated. age would say not I that of the the into patients, in as considered take

We it's your clinical still that, defer right in But now are the landing similar point, I'll Suku little a early in on and to to spots assessment. with some the question.

Sukumar Nagendran

that both important should That's patient, these where not struggling the maximize to it frankly, the to the we, also the the XX were does given the very mind assess actually understand a XX-year-old severe there over caregivers be And an patients think time. XX%. period that because So we keep score parents are females, question that adults, usually in or by in more did I up are higher done used are who them expect XX items to assessment. mind of And still assume were important I to they the the in see and and the right? score to effect. is RSBQ -- It's much that keep scale, XX of

is their or have they patient the or child a over to of so. a So doing course on reflect week how

and as as be score starting the sicker the because much may lower the is drop patient, the be sick, the with more the significant gene they far well.And the I the some patient is while can score then who as there are being not So the effect, observing not at variability as higher a a think drop finally, in what ceiling as being there baseline. greater assessed therapy we are the

question you we RSBQ And patients few the data. I the can dose is other in more little with answer thing and then question. have I that more to mind your a think probably once a keep

points. XX-year-old approval. a to RSBQ that because drop not asked you worsens the combined in study, use at did the to was actually RSBQ, caveat combined trofinetide endpoint intervention.Now time. evaluate XX You frankly, designed CGI-I get is questions was the have a the evaluate the with X to look look only over to if process been some have to at being developed for the questions And RSBQ their trofinetide group, therapeutic of the that disease

terms, first So milder showed like disease though has doing second even point comparisons, patient cross-study the X-point I relative patient our I guess, and don't and in had drop, a XX a much drop. XX who a

Sean Nolan

severity, the was And -- it

Sukumar Nagendran

And right. the That's severity.

Gil Blum

question. I is is very early. My agree. This This more purposes. educational for second

disease more So increase to at would patients kind adult signal look just as to to segue, the be of severe noise? in study, it beneficial hypothetical a with a

Sean Nolan

show with wasn't basically or difference severe enrich you generated they there theÂ trofinetideÂ data, -- to off the effect. It's saying their are study When you're bigger -- essentially p-value at patients in effect really CGI-I patients, severe a the there much interesting, Gil. but look Yes, more

Sukumar Nagendran

RSBQ.

Sean Nolan

to inÂ mild RSBQ moderate.

So one. your point a good is

to we're have different, so see were more to be this the could I I definitive encouraging. still treatable here more the about to think and were patients, was But get answer. different think, that the seeing we what what's very is genotypes exciting us we continues and like fact response that significant. Again, to a the corresponding population phenotypes so remain yet

Suku's reaffirm So I patients. see more point, to would say some let's

well. Let's certainly that And trial about high dose will we inform as B design. think get part endpoints how and to the

Operator

Fargo from Wells comes from Zhu Yanan Securities. next The question

Yanan Zhu

as sounds big I patient X-week #X's is bigger, and points improvement. improvement much patient and that So than #X's I have improvement R-MBA. X that's as roughly And question on think the if correctly, I a #X, I think heard this R-MBA patient and like bigger XX-week

despite comment quite in I And be that milder to the X provide if on baselineÂ R-MBAÂ score improvement maybe for can the appears why X great. you And would can or If be disease striking. patient, R-MBA patient, of this you this have follow-ups.

Sean Nolan

patient your were, one, was it XX. the scores for to baseline So point

For XX. it's for X, at X, XX. patient Week patient patient is for at was two, week XX, And now And XX. week one, XX. two, was one it then it at patient

a X drop get two XX over and to this. What question. one was weeks over try a weeks. been to rest in And your X-point driving the over drop patient there's it patient turn at then Suku X-point So in to of I'll

Sukumar Nagendran

Right.

R-MBA goes of think assessment well, a And scale. components. clinician the a I because the has can our question an X it that's important on and patient it up score So as as of, to is you see

such bruxism, sicker, show who when which we a score shifted was right, was and to not manner R-MBA improvement. R-MBA by some also the worsening, fear evaluate and patient much my the increased given show cloud milder change, knowledge, right, score influenced actually in anxiety, much first the patient the been arranged patient previous already But the patient, that didn't patient and assessment. this actually, that of actual of function said, in not the The this face, And I is severe think, set did the the questions these muscle the have is questions had. therefore, positive masseter because in of abnormalities the where as didn't one in was asked therapeutic assessment I the disease, that though, increased to necessarily to this a to muscles, bruxism intervention. therapeutic has In there's the validated that were experts, R-MBA including some has But patient two, designed response.And of actually they positive. as understanding were never up, talk disease

these eventual questions to really guess I Kamran, measures So want understand comment to are you you to of And that? need of that point make some my on is within what do again the the sense numbers.

Kamran Alam

sure. Yes,

of some in Behavior So the Motor in and skills behavior. the -- respiratory social the were improvement Assessment, terms Revised of

Sukumar Nagendran

hopefully I add the assessments that intervention of would validated therapy, the these to for sometimes need I is have mostly these can Right.Â So assessment. patients, been punctuate also transformative not that say overcome each guess what and therapeutic though, point for I significantly clinical a for of if scales especially that will

Yanan Zhu

I'm similar many that it the trofinetide, can what to follow-up -- in improvement And patient what that of with X-point on you #X, for wondering, patient this then clinically. Could patient you RSBQ, hand, I have had sorry. But had if also, this nature severe trofinetide, which example? on other just treated about that is? the improvement achieve. differ the patient? could My sounded was how saw you the comment like so, trofinetide sounds for patient like is If improvements patient lastly, with in And what maybe been identified in compared the

Sean Nolan

I or of was when that X. Yanan, with the disease, RSBQ impact would trofinetide patients you say the had at question, piece look the mild moderate on

fine on out person definitely moderate. by said, So gross demonstrated scale. the or socialization grade would motor that a was particular And primarily skills. that was this this mild And in the breathing, the particular we circumstance, it you impact and X and as driven we as the

of through not the LAR which which we've across like by being the that point, there's is in to patient forward year line observed consistent of the forward we're QX seeing And the by the it is why seeing process, landing, that's scales So this next which physician that their next assessments very I about at why adult relates at comprehensive to which modified lot domains, of nice and QX the to She I in the ballpark we're congruence it's the think have we again, becoming -- me, And looks of which her. couple is guidance week have what's of patient. don't being think same a dosing very past, and see observations things XX gone we're correlation to moving area. right an would to getting absolute with where I more first final And patient are table.As yet And being talked put we into it feedback year, say that it's the has to I getting and #X, be, observations. some a a a with assessments where sight good is scales, to needs across product a she's put which Suku's direction levels along are the identified to think, her clinically. XX from its testament is play, clinical parents we MECPX is And response where screening. the is behavior which XX.So in and is at to. therapeutic landing it the the is stages

window. of So we there's holidays where that should given the you, windows can the have And the time slot know what institution, it in in. patient within and be

year. We just possible it We'll characteristics So at QX year. keep it's this know not apprised on this a baseline do stage But any that. next we particular still patient. do could be you It juncture. that would X know be

Operator

from Allen from Baird. The Jack next question comes

Jack Allen

steroid given around that the post-dose the taper? here. to some context results have up the So in you more from steroids are I was results -- therapy? confidence of regimen the short patient different a steroid you are one due in what degree hoping any of could And that's that impact how could the term context if potential these from provide do shaping in be potential post-gene

Sukumar Nagendran

Yes.

These on of therefore, then given. gene been protocol, therapy with prednisolone, patients experiments form seen impacts and this a the what's much the used that a after And to bothÂ prednisoloneÂ and minus actually has into We've all all milligrams off talked actually no X say they runs, any based the have will day some also sirolimus to milligram recall, age X.XX. per the impact. no of XX and surface clinical then X.X and literature. that be treat they kilogram are continued over per X, XX said be it have of that. weeks than starting over for looked get the patients kilogram area certain X at be all around done who people syndrome, from transplant then XX or way body on day if due dose is will Rett it's also tapered and and sirolimus I So that the the improvement will who number tapered a there started minus weeks. out and to down in experts lower extensively disease.Some progression weeks, to is We've too, disease And the for

Jack Allen

moving you it given then of modifying two, potential to just on patient sirolimus the dosing that as forward? And seizures any dosing that relates implications to have consideration the and had

Sukumar Nagendran

very is with Yes, into the now some to could AAVX we be the showed to as experience therapy if especially we've working of patients drop sirolimus gene said, you that, But issue is the is GAN significantly DILANTIN. prednisolone medicine helpful, actually given in actually and antibodies, -- which that program, especially the looking with where I've it, a our dosed higherÂ seropositivity. but with with is type that have balance regardless well where like we adult started what seropositivity patients have there anti-seizure used, we of as being levels do happened

sirolimus. are So that question the through are is, can not and liver by medicines I there way impacted processed other we bigger try, in the which a negatively guess

something we to assess that's think continue for that I now. have So to

Sean Nolan

tried Yes. I that is other theÂ DILANTIN.Â And was that would products least was to history, seizures andÂ DILANTINÂ was patient multiple work. just one add her the the at Jack, the that control X only she's based to thing, it on that, appeared on to

be in bit we it proceed may unique see monitor So a and a the have carefully of study. to as it circumstance. just We'll

Jack Allen

progress. on the Congratulations

Operator

question Securities. from Truist Lee Joon The from next comes

Mehdi Goudarzi

the on is Joon. Congrats This data. for Mahdi on

design, dose to administration, GAN. strong Could I question, have differentiator a of Neurogene second on close you in your of therapy from to I capsidÂ seems have direct Rett is which of a could a you your TSHA-XXX routes mean, in because please NGN-XXX. And gene viewed in the the that as be elaborate program So levels, same. anything construct competitor program? specific be related syndrome from

any are the takers going this there there on -- any negotiations latest program? or So there what's are for there? Is

Sean Nolan

Thanks, Joon.

Let's a start with the GAN question. to would say I lot not on specifically. comment there's just

are that anything the stepping resolved. alternatives. outlined in it's to And of strategic we've We through on until comment been want actually process wouldn't I

on tuned report specifically. one, nothing stay but to that So

where both high level toÂ Neurogene, relates constructs that you're as similarities use of correct be I it guess the I AAVX the would could As couple capsid. say a things that's But end.

minigene, a have have we gene. they length #X, So a full

Our are promoters different. slightly

take it's would the able on that into each MECPX, of exogenous regulatory account way I and create And miRARE will or think either really the levels it based describe not. is that the exact of key read a I aspect it level MECPX have.So cell versus goes the MECPX technology that construct element, into. in endogenous our they the is endogenous we that to have

of I feature that's regulates distinguishing exact where endogenous the taking is so And MECPX. technology into itself, that account the understanding is think essentially it our levels not of the

we're that's embarking potentially, quite with don't route in team differentiation. setting, at clinical just but Neurogene anything also just area construct. And time, the just So go we're a would and overexpression.So delivery theÂ NeurogeneÂ program. differences. at patient that intrathecal proof for could severe ICV saw is upon Joon. we're comment I in And concept a coupled not note we're question, low a I have that I'm of going we'll seeing not very overexpression very mutation encouraging, that I of And We risk producing you that back hopefully, of would through construct But point her expect less phenotypes a response. key we're severe seeing X asked nice I the with where patient find any genotypes first signs MECPX would that Whitney particular there.So our with out MECPX, say of be seeing seeing that the fact to versus response there of with the your and levels question with additional anymore pleased significantly more these in and on I specific. aware very a would in there's a with different this -- would is right? we're to lot our what can't that arguably gets construct. be the of

Mehdi Goudarzi

again Congrats, data. on the

Operator

The Instructions] question [Operator from Silvan comes Tuerkcan Securities. JMP from next

Silvan Tuerkcan

update great here. the on Congratulations

does of scale by improve? important on considering that's the very measured duration? quality just the I How one And of does you and the sleep device. is some one it and I also it sort measure pattern, breathing a think how how measured, here. assume measures? site this variability that and they're is of single autonomic function comment objectivity can Just would investigator, especially trial

Sean Nolan

of of those say different by people. I measured -- that would functions Yes. just scales a different and are there's lot both via

And to and they're examples hand function, independent going clinical Some they're administered measured score have that be the function going whereas being CGI-I to the are that. clinician. That's seeing clinical of of with review be to sent like assessment, be good example, that's RBA. demonstrate we what and what's RSBQ at during an videotaped to the do to by like right? a or the the to That's PGI, that's party is them a going going there. the happening measured log look in example, then we and caregiver motor an like And when her as observations and

So to more Suku, add I'll turn it you over to color.

Sukumar Nagendran

these patients. And Yes. seen abnormalities, your with I in autonomic also, think right, reference to question was

break you. down for this So I'll

Montreal, in have have of physicians in this into a patients time. care taking center have these been adult referred for do them remember, they long now who So been single very who

also observed. function. sense So are seizure seen possible a to in abnormalities how parental lab measured the that happen.And evaluations in you and have patients sleep you diaries, dysfunction, Also, the When to may it appropriate you depends often activities and history to usually, function there that these sleep, have these history, have good then seizures but also with mortality give that GI it the medical GI clinical GI or sense also that do when studies reports, documents when it comes seizures, sometimes, it diaries, usually be. of you abnormalities comes been how on could documents seizure EEG abnormality it respiratory that are sleep whenever the comes that give some abnormal patients

some are protocol. or subtle respiratory sleep are abnormalities, continued those general And to So over make the to some patient questionnaires dysfunction? may obviously, these obvious there does there the the questions scale motor evaluation And these assessments. the Are cetera? Are collective abnormalities? are give of you treatment that it's questions assessment referring then as then continued per of parameters hint used assessments have each history past on there was that or finally, then Sean that PI, of So time. based post et a continued

Silvan Tuerkcan

the patient, is switch regarding but -- higher the higher post there third DSMB the dose not then patient? the higher, at just dosing dosing another to going of meeting the required of dose, the the third to And to

Sukumar Nagendran

database, weeks the you XEXX. you X IDMC DSMB go the of cohort you collect then is higher have meet with to dosed, and and before Yes. Once patient wait you the then the clean or third data, the to dose

Operator

And longer Yang and the It on next like have closing remarks. question-and-answer are Jefferies. time, further we from The back like session. we turn comes there I'd question for YangÂ connected haveÂ Eun the Eun reached gentlemen, you, the Sean. And to of in questions the queue. Ladies this Nolan seems no from line. Thank Sean end to call at no the

Sean Nolan

call. thank forward questions Take We speaking attending for care. the to again everyone want the Just soon. to appreciate look and

Operator

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

You may lines. your now disconnect

Taysha Gene Therapies (TSHA) 14 Nov 232023 Q3 Earnings call transcript