TSHA - Earnings call transcript Q2 2021 | Taysha Gene Therapies, Inc.

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Operator

Welcome to the Taysha Gene Therapies Second Quarter 2021 Financial Results and Corporate Update Conference Call. [Operator Instructions] As a reminder, this call is being recorded today, August 16, 2021. I will now turn the call over to Dr. Kimberly Lee, Senior Vice President of Corporate Communications and Investor Relations. Please go ahead.

Kimberly Lee

to conference quarter call. welcome and financial and update corporate morning, Taysha’s XXXX second results Good

funding for session XX, remarks, Taysha release Prasad, and Joining press issued Session question-and-answer will Alam, CEO Suyash II, commercial copy the These patent discoveries, controlled on Chief of results quarter Taysha’s the conduct at drug clinical by statements other Medical protection of relating filings. to me strategic future preclinical obtain our call and of as status include June and safety owned stated manufacturing our forward-looking uncertainties dependence Taysha’s This Various patient today’s those of forward-looking those alliances potential results may through substantial relationships; our trials and related and to our President, ended the of and limitations and call to statements or such drug regulatory Financial we operating may imposed and the include our Officer. requirements this Founder; statements Please formal upon from and press and and and website research of second activities. also SEC timing programs well we forward-looking our and R&D; making candidates growth candidates. and A efficacy cause or release results, be including Head are studies After as is will plans. conduct to statements strategic risks that discovery are RA Chief of follow results call, implied ability and statements. of results the Kamran available contain Officer our timing XXXX. a development well information. announcing today’s trials development differ expected market instructions a for clinical time. drug today, opportunity property as financial the and facts Earlier our by for will company’s intellectual materially or investigational risks candidates, third-party the drug candidates not Taysha’s on relating the third-parties may and alliances and Dr. note patents as in matters historical that to therapeutic on to that for and the These actual or

For information only I’d Exchange to turn Securities we of that, statements and list reports the no Founder, this the obligations that RA as and revise accurate face, like with have update conference With August or description date by to circumstances and this a the that applicable risks conference Commission. is to required uncertainties date broadcast, II. President, of and the reflect we securities see please Session after or laws. call, XXXX. filed time-sensitive any over contains of This a call call except forward-looking the maybe Taysha as the undertakes events to our XX, of now CEO live

RA Session II

announcing and corporate results recent our Thank highlighted conference several to significant on financial were welcome make update achievements initiatives, and XXXX. second corporate manufacturing progress of on some our Good and at and elaborate you, our clinical, and press will Taysha to morning for Day our Valley remainder as the call. strategic everyone Kim. Investor recent which quarter continues key with key milestones R&D well expected Manufacturing review our Silicon I the as release financing Bank. of non-dilutive recent

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supports robust, tauopathy novel on syndrome. manufacturing we review MAPT-associated our runs clinical further material our across support Lastly, numerous high-quality will consistent treatment GMP Manufacturing we of Phase to our approaches achieved pleased de-risked announce portfolio high-quality on manufacturing our approach, the several and to that shortly. relies held Day expression July, our disclosed we effects IND/CTA-enabling how and two Suyash that for tau our integrates of and have clinical X Part which of success X/X In seamlessly studies. planned the TSHA-XXX these and and highlight and trials scalable flexible are overall Angelman sustainable broad delivery support in we a our successful developments pipeline. R&D and that to pipeline portfolio

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gangliosidosis, GMX track and remain to year. For in the first-in-human this report biomarker we safety of HEXA second on data half

Mary uniquely including clinical the our talented Vice development. positions in the At Officer. IND, these which our former development candidates teams, and numerous anticipate platform. our was dedicated Development formerly The Astellas The without the of dosing and and support expertise recently For years rapid year and advancement has collective of brings candidates programs Senior Southwestern We addition possible of affairs. manufacturing management year. end, Collectively, and have we seasoned including in program regulatory our patient translational be of renowned She employees of a clinical Regulatory first colleagues an now open at care. experience translational over XX X/X currently we Directors Phase across of Taysha, that multiple in functional have trial dedication as appointed GMP Chief we in our development, Newman to will the will at President of development, Affairs team. Audentes areas, we our Advisory of not internationally therapy by anticipate X Gene program, XX our CLNX in and second half and Board, UT gene independent Scientific Board Therapies, XXX technology across discovery, expedited this

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Suyash Prasad

Thanks, RA.

progression assessment At we tool, a to of new ability the clinical clinical X/X with in compelling upsetting preserve visual halting acuity GAN. there blindness, with from patient AAVX We is approval regulatory lost. potential patients a i.e., towards understandably advancements to of and significant of vision data we stabilization of disease most this GAN. which quarter data, challenging new the dose-dependent the established an from demonstrate have ongoing patients adolescents achieve would further Phase GAN, which continue by assessed ongoing perspective be the is program, giant In or neuropathy, made the advanced and the most significant family. second to TSHA-XXX children able trend symptoms Day, progress well-validated gene athermal and data the towards progressive TSHA-XXX, with the With acuity, that in one addition otherwise deterioration function, MFMXX, trial were which therapy and of and visual of for in motor promise investigating visual to our presented in support R&D the holds and important demonstrating our as

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This phenotype strategy Day, with that in For in in Leigh increase TSHA-XXX data TSHA-XXX. correlated these only our demonstrating a Reduced SURFX significantly activity tox announced supporting can at clinical worsening patients, small with disease improve activity SURFX-associated replacement further in syndrome, new fibroblasts, we COX-X also We to R&D the patient gene increases of IND/CTA further are can pronounced plan phenomenon of outcomes. draws have this other impact the GMX supporting COX while year. CLNX, physiological including and disease an second targeting, TSHA-XXX to small for we half in impact. a on activity diseases activity in that the correlations file

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the response dose our from now We preclinical experiments. pharmacology finalizing are and evaluating age and dose

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We presented tauopathies. an treatment to currently to Preclinical are continue good use tauopathies protein and and levels of trial validating both demonstrated silencing TSHA-XXX and at levels, achieve protein tau programs reduction R&D data reduction developing on lifelong gene for significant protocol. preclinical of of further progress make in supporting interventional AAV-mediated the for potential Day mRNA tau development in the

Angelman novel very were on we approaches Day highlight our at treat to excited R&D syndrome. Lastly, to

are population paternal to a of UBEXA unsilenced We gene targeting using and allele UBEXA-ATS the knockdown mimic expression. to maternal the on also Angelman allele strategy syndrome entire UBEXA the via replacement

have cerebellum following compelling the of UBEXA demonstrates We TSHA-XXX, hairpin images of fluorescence administration RNA expression that shown short our candidates.

robust As our of and advance expected have as half number catalysts And preclinical of in RA clinical see, we the expeditiously. to the regulatory a portfolio continues of clinical you can noted, and candidates year. second

We will With year. I to will turn continue results. throughout over call updates on to our the review provide the our financial to programs that, Kamran

Kamran Alam

Taysha non-dilutive Silicon with Valley a financing million of financing secured Suyash. XX-Q, has morning, second financial which closing, Bank, our found you, can $XX term drawn Form results. be be up quarter to This at $XXX recently available million which We key SVB, will our aspects More in shortly. or discuss SEC recent $XX million. our the will details non-dilutive loan Thank for XXXX I filed and with from of

Street Wall warrants plus financial to extend key our certain believe financing. financing. drawdown GAN potential through interest and will We prime of remaining for the drawdown no this rate regulatory Journal are covenants milestones, is subject additional the The including approval or conditions. of there value-creating runway We to option in the this cash the X.XX% X% or tranches full multiple have of TSHA-XXX greater with a funding without need the that rate associated

which clinical compared clinical and expenses GLP XX, the the included non-cash to to our and as for or second ended million toxicology XXXX. the primarily employee consulting June ended studies activities, raw by on, in trial compensation expenses, million of were release fees. $XX.X compensation months June June in incurred to Moving months ended today, attributable increase research was X million ended compared stock-based and Net million June for ended of $X.X and $X.X XXXX XX, million, million other of $XX.X or to million and regulatory includes an and for XX, expenses for $X.X attributable second batches net increase purchases, press a to was R&D incurred quarter was million studies. the June the The were $XX.X per and indicated CRO second $XX.X The compared compensation XX, million We quarter additional ended consulting professional XX, XXXX. loss for of June expenses XXXX X non-cash XX, G&A manufacturing $X.XX in an development, CGMP second the share of third-party expense, loss $X.X produced for primarily quarter which UT research expenses included compensation per increase $X.XX quarter stock-based in included incremental $XX.X XXXX share as which and Catalent and $X.X which material for increase million Southwestern. $XX.X million XXXX. development

and hand RA. in $XXX.X from announced had back will debt million As that, XX, And the include financing. cash I XXXX, equivalents. call does of not June to the This cash with Taysha recently funds

RA Session II

Thanks, Kamran.

quarter. the to pleased are success have with our you over We shared second

update motivation reiterate the and TSHA-XXX pipeline milestones of including regulatory Looking our in X/X preclinical the program, and from executing our We now the continue of GAN curative to biomarker ahead, the expeditiously Rett continued reporting syndrome XXXX, who give collaborators, trials data the and for highest regulatory session. begin second and half Phase and GMX Southwestern TSHA-XXX our reporting Directors, employees, clinical, our will to and for in we of Leigh Phase milestones key therapies. I CLNX support continue on I in guidance advocates safety Board, advancing to from thanks and X/X and second the data X/X XXXX. in study dose expected gangliosidosis the preliminary syndrome. ask our in patients Phase mission of on gene providing the will remain everyday to the Board operator half disease, our anticipated to dedication cohort Operator? a SURFX-associated GAN, would Scientific develop UT special for initiating Q&A Taysha focus Advisory like

Operator

Thank question the Sachs. Please of Instructions] Richter proceed first Our line from Salveen [Operator your comes with question. Goldman you. with

Elizabeth Webster

is morning taking good for Elizabeth our question. thank Hey for Salveen. This on you guys and

you have pre-IND Just on present into positive guess the on regulatory and little And more in – ask releases could more data approach CTA of broadly, agencies? the of that the Taysha’s venues of XXXX some wanted if to bit I just gotten to could a the provide data feedback then the what from nature are forward? color Taysha just and second half you the

RA Session II

What Sure. regulators. take morning. question and I will first first and – I the and releasing an primarily the to is call. data some is release through discussions will give good question either question will some will to of I do Thanks, and/or throw then then Essentially, with around Elizabeth take our sorry, recent doing we approach press second Suyash the to our be am investor I to color going

of we Investor months. Days mini these done last a the kind recall, you As over number few of have

First is our R&D Day.

The the Manufacturing was second Day.

Investor Day CLNX few the Investor syndrome the followed next our Rett our and Day. then have will by Angelman weeks in be that Investor here and Day We coming up

going to available release. is on of the And be so depending when timing the to data

times going around just do to of had the maybe additional provide release, our it more have regulatory around do want some so the color the that well, half we call We certainly would a are come, release you last over second press through which interactions few but as primarily a provide press obviously number color interactions of of to last may we to over you the some exciting it that months. general to months, but either few the Suyash, for some year. anyway,

Suyash Prasad

Yes, for question, and thanks RA Elizabeth. thanks the

have few past that schedule a regulatory of very, was months had We the very purposeful. activity and hectic over

know, to programs. of you our each for our multiple As with engagement, in jurisdictions regulatory approach filing are we

we close have The And probably which regulatory other had very, good. countries. and collegial. been XX general, the to So interactions FDA has included they tone been have in several very

their very been have questions. answer able surprises We few to There has all been along the way.

I the be them three say And on fair think our once approach themselves, of programs. of that we have a similar topics would very I’ll it across and to few and again, large that a categories. actual CMC potency focused is to acid is discussions testing. we note, a bucket part One

way word looking early. We a very disciplined We potency. all the of at have start

that well there general no is discussion So goes and surprises there.

and differences the to But terms time comprehensive. of bit and of again, in agencies a species very as agencies little little robust could what combination On a are, chronic plans X favorable we of a general, in very X-month of rate all tends programs, across tox, tox more mouse FDA is be want which our robust expectations some all to there. the and There tox less. once X include non-clinical And of know, little duration have conservative. is and want toxicology we more be slight a which in most some the side, a few agency And the package a very our NHP are months. i.e.,

in key and sub-design So We our And we our – give the we developmental leaders, question generally multiple feedback thought the the videos favorable assessments of disciplined once of from endpoints. we’ve usually again, and studies. progression clinical a a tends a are end those. third protocol write the bucket are from way. on and around robustness patients very agencies that to in and that be of the majority families, sure to lot had we’ve to to very adds opinion feedback for points And make

discussions go again, once well those so And also.

lots has of I that we and been interactions, little positive say the and to collegial is So really more lots very of far. few interactions, engagement have good thus very But very and a come. yet would surprises there been

In we’re seeing said fact, What last one of to you forward next at to time. looking the the meeting. agencies us have

think the that’s conversations. just signifies tone I So really the of

Elizabeth Webster

Great. so much. Thank you

Operator

you. Thank

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

Joon Lee

Hi, taking question our for for and update. the thanks

which I a after one, micro initial have Rett altogether the you. you in-house clinical syndrome, that programs. the mention to your response Or indication data biomarker follow-up also, of favor the us skip interesting skipping clinical – larger of the and a stood And release. active you given a for biomarker disclosure one by data? data but planned ‘XX, the you know-how. really any are relatively element, in And quick is just out So more is press data This biomarker protected that. to data disclosures a other to something Thank patented? is planning this guided Are year-end no by of in is released the

Suyash Prasad

regards take great CSF can been to the syndrome, scientists many really isn’t and a the the it’s question good biomarker there wish many, a question, sciences data, a we With disease. good But and Sure. for clinician biomarker. biomarker about expert talk Well, or can RA IP. a then I on blood-based looking for had biomarker this data a Joon. I Rett good physician sadly, have biomarker biomarker particular for the

of mean we to the is Rett biomarkers, The modification it’s early probably from efficacy with established, activity not why very But perspective the if thereafter. to see plan that will from biomarker not biomarker, we the for the a of possible we EEG. which an specifically is a and Rett with share see what robust, and I best in have, very biomarker very as of day. then think I very EEG think which on a good, hope abnormal, to don’t regard looks retro a early EEGs something safety it. biomarker perspective really children I good, that that interesting guide we it’s best well-accepted is is the drug. the see really But we will

metabolomics however, and collecting and blood We are, full performing analyses. CSF and proteomics

interesting will don’t much been see does because biomarker, experts an hope there. something hold for up crop So a I looking it long biomarker then many, have for as useful we many that, time. for frankly,

and do to So And the over enrolling study end of are the XXXX. IP end the for question. year by we study the by data of ultimately, – to the start RA guiding we I’ll in this hand now clinical

RA Session II

Joon, thanks And for question. Sure. Thanks, Suyash. the morning. Good

property. covered intellectual by So platform strong our MI is rare

about of We’re and the ability dose a protein. but cell-by-cell on the not may for show broad there platform be this also platform the to indications other genotypic basis to a where exploit that the to nature sensitive pretty expression excited applicability MECPX only

so is a of FOXGX. to them, really in other areas, being X another, correlation Angelman there disease of this lot a Fragile And nice one being Pitt-Hopkins,

same is binding number new potential to where into the to of sites So use binding sites subset disease have the itself. – a these of you pick microRNA a transgene depending exact to microRNA or on the build there either to another

excited So it. about we’re pretty actually

very gene to approach gene if I therapy recall, that to And approach payload is you technology, to others. with therapy targeted significantly our design. is really something coupled use think validated it differentiates our

innovate around So piece, really an intrathecal AAVX that. delivery the important HEKXXX am and I being but of suspension validated piece rare payloads

estate areas, expand in continue we other around to out continue IP as so the our will disease that. we data build obviously, And to set

Joon Lee

given quick dose starting other you. AAVX all between And the programs comparable Thank doses Excellent. escalation are for your also the all programs, vector, you. Thank use all is your they comparable? And for strategy your follow-up just programs? a

RA Session II

our in using it kind maybe Suyash, using give that again, good approach to validated technology exploring platform you this this approach. really, Really, speaks multiple think And And want question. indications. some thoughts and that to and there. of I to

Suyash Prasad

can. patient Sure, I It’s the in I for approaching good a general, And are say, dose first yes, in we program. very each would question. each

would has high as I aggressively direct it a we terms I most exposure on GMX thereafter. you things of for in And or say that it our where way. bit a no programs, have up The What low doses differ so where enzyme or total really. have. supraphysiological cord the a as escalate systemic in programs which And overproducing of vg couple dose side, impact being know, similar actually ending dosed a window depends the of would actually a secreted several are enzyme, – we little actually bit can depends therapeutic have thing quantities example, a where with around a of which detrimental of accelerate goes for a on in for a compressed relatively CLNX the and drugs you XEXX [indiscernible]. spinal therapeutic vg, can little – long of is we you for systemic ballpark We’re converse window, to actually is whatsoever. on broad enzyme dose brain in the But is how important very bit

which relatively a you So there know, narrow Rett dose for and the then are such accelerate those as we as programs, and escalate rapidly. But is window, where, quite in have more we in can therapeutic we there programs Rett. be fact the for or a platform, that regulates MECPX produced cautious proportion to bit dose, the self escalating accelerating the of MRI have that’s the being despite little

ballpark, therapeutic on each have slightly we higher, the program. the generally the say we same window but we rate I is then for So do we start that in in dose would different escalate as that a dependent

Joon Lee

you. Thank

RA Session II

Joon. Thanks,

Operator

you. Thank

from Our question. next of Laura question the with proceed Securities. Chico with Wedbush your comes line Please

Laura Chico

was if runway dose cash wondering to spend then this now? just the for just think and a taking follow-up, agreement expectations estimates? could around morning makes And first wanted that does how my clarify, you Good why much minute very question. in just sense Thanks the guys. the the I And you change on loan XXEXX My for one, perhaps GAN.

You’d seem have to the already lower at an doses. effect

So very advanced just Thanks be would trying to which doses much. or dose understand commercially?

RA Session II

around the take Good Laura. do morning. for first dosing. what And I’ll and question Hi, Suyash, GAN over I’ll financing it the will turn is to around then non-dilutive you we

the low way think accurately not non-dilutive gene a – reach necessarily innovative volatile opportunity the where to additional bring the as add any somewhat was we data clinic, capital particularly, rates, equity for in capital. foreseeable without readouts to markets have the finance. situation such historically opportunity therapy to and because the good valuing we’re the are time kind number about a that capital as the to to need strongly environment in and And a here and later a companies. And programs we opportunity this robust a thought where the GAN ability portfolio, kind approval even we for cost felt in a of timing on of is year an this the financing, we that we come number of a perspective, So and of the this this at of from had this future really

that the We a couple about this I things is with low get interest a about able we in of X% single no partner be and along We attractive. as is to goes about financial I rate. think, is with the warrant that that talked in covenants, deal you think This rate coverage. about has do a to Bank. it historically were – deal interest can talked one which clean this terms name talked a Silicon a Valley of of the no quite credibility,

trade-offs so because thought have literally wonderful to capital multiple what’s slow the partnering being dry optionality. we and this to with announce It’s And move That’s not data with into about for and SVB was to any all able to to can’t to equity the we add predict this make about, second get just the markets, half to able in down all best-in-class forward us, to we being additional a next or necessarily it’s And anything particular going it. able as things powder being get tank. deal year. And about happen able readouts. of some into year this again, pretty were be opportunity we the excited

high I’ll come, these pause XXEXX Suyash so XX talk to versus dosed open the more of and vg pathway Just and total We’re data, you GAN, about to want trial, to to and the these there regulatory maybe first on feedback and dose. right? more GMX about the CLNX gangliosidosis, total dose of turn vg biomarker Suyash, around Rett over syndrome clinical registration safety patient talking X.XE data, GAN dose it

Suyash Prasad

the you’re Yes, Laura. right. for question, Thanks Absolutely.

very, progression the As at dose X.XEXX that good. We looks disease very clear dose. very, of very, see stabilization

And some X-point XX contributable just clinically an time we at basin XX.X% of years, so you in to that and who improvement that that We chance when have X patient meaningful. sustainability relevant in which improvement. is – halts have out effect of a etcetera. have MFMXX X-point decline the meaningful clinically the patients these over debt. and corporate translates points clinically dose scale, the dose, showing slides every in quite dosed analysis it our i.e., run know year, also We our that X.XEXX improvement a is will

be when is going and the a NIH, solid dose. total at very, years, up be really other it’s way run So dose, What that been on drug set to that approvable is initially the would Carsten NIH. XXEXX very has and several I that’s study And for been a vg. to this to out Bönnemann will all nicely. the and response frankly Carsten run dose say

patients approach these wonderful relentlessly you the that data of death, those better. clinical What meetings X-year towards at we give a And end regulatory most my as this chance been say dose, or of we significant of have that Now medium data I them year. this will really be best will high to having the time have deterioration with the on progressive for patients benefit. we every have the neurological in is will second this dosed on as to our guess children year, same towards slightly of show the package. the have And three the this three and least higher either dose share X.XEXX put is actually those patients half at

We as package. we know, And will the you study. history great part have XEXX natural have this as dose the of

responsiveness. dose have We

We have high I at in high the medium be expect dose. clear stabilization of there same the dose. least disease the the at will

efficacy long-term safety, long-term have We long-term durability.

to the said, up well. than dose. the X.XEXX am forward of those looking commercializing, will I But probably as would as the more decisions regulators. I X.XEXX So in having likely be But I think be terms it with

me there. Let you. Thank stop

Laura Chico

you. Thank

Operator

you. Thank

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

Gil Blum

everyone morning for thanks and our Good question. taking

therapy? thoughts way do I So have IT FDA have is follow-up. And the guys the clinical think views a hold any a on change gene on the recent benefit the do And you administration? of just this IT the lifting the Zolgensma you risk for in AAV

RA Session II

additional Suyash, some Good start, and Hey, provide please Gil. comments. morning. I’ll Maybe

patients over the out And the essentially data or think FDA on sustained, not again, I effective that clinically in formulation twofold the see but X only meaningful Zolgensma study considered the really Type where conducting improvement population. was X and IT X we dose. that would that seen intrathecal and in a patient us, what from think demonstrated also excited come to that be hold in the we’ve safe Phase were Zolgensma, a Hammersmith significant a with I the original the lift study the for ago treated clinical week the fact going to Novartis news we’re were did actually so about that be for the

deliver we has also extremely were CLNX then studies Zolgensma. had in clinical recent CLNX supports effective the we our but about it. the to excited of is of perspective data. be in way quite data, an own about administration we from and and both AAVX talk particularly enterthecally, efficacy to but and from Amicus able genome data, has Their And the a This very like totality felt safety combination an been again, again, also to which think, demonstrated phenomenal neuropathy We the think you perspective, of again, CSF. when so route trial, by directly around And that. the study this

gene over asked toxicology of treatment now fact X,XXX as the efficacy monogenic been has Zolgensma and on conduct the approach agency really hold globally, the fact using diseases. so based And some to well CNS results, lifted the to XXX the think, I so they that AAVX I sorry, that matter a safety NHP speaks therapy the for in conducted was from perspective, patients that believe of additional of Novartis those data again, the a toxicology think, clinical and regulatory I

and feedback And gotten they where very this approach then the mirrors the have some in agency, recent go package additional we’ve to of looking taken kind of are so again, tax have I comments. think toxicology know with of in the I’ll we pragmatic from with there. your probably that stop three cases, what species some they Suyash, you dovetails for. I this fact nicely most a

Suyash Prasad

Sure. Thanks, Gil, RA, and question. the for thanks,

Both gene clinical year, X the in to X.X for holds. had years we’ve gene down with safety CMC-related I clamping has where space. have FDA that therapy AAV been and for think the issues I seeming the Actually, matters And Pharmaceuticals we wonder hold recently. announced also of Zolgensma the again, Rocket morning, if now. this changing therapy lifting once AAVX have we the hold lifting for the that’s program. do Danon

are So bit time if the getting a I shift more more they in comfortable little therapy time less and is spending a on the of there just FDA been a of wonder and now. on gene COVID perspective

good It’s transferable definitely wider AAVX. the to it’s product, Zolgensma our with specifically for think AAVX I wider space. news

ranges. scale that study into that’s on slightly children data very Type is which the and used clinical scale, obviously, are the going the Hammersmith and older intrathecal mentioned, effects And was meaningful EXX a CHOP-INTEND because already in very, you’re X clinically Type X. SMA for actually saw As the from the positive. We trial doses strong a in

you that’s again, been have NHP the once translatable as now study. for issues to The programs our with quite a So listed well. learn lot can safety

very to toxicology, it. FDA, for been the for I’ve discussions is our robust. very an have in already And as accepting mentioned, approach they Our acceptable thus far, with

the AAV for well. disease fact for hold this of a little this hole morning as the hoping shifting the off was I’m the Danon FDA’s But news clinical good was lifting Zolgensma bit. is So that as paradigm

Gil Blum

an the Would sufficient initial and conducted? for that patients us mentioned? idea And runs you all of that give can with of you’ve your the these you number for be programs clinical maybe you color. you thank that treat currently the the Alright, could studies GMP

RA Session II

really what GMP and cohort consistency but clinical for of we giving it’s absolutely having a make only tox IND-enabling trial want GMP for package, adding certain necessarily we GMP and run, appreciate another also go a same having in by set doing a correct, then not a is are treated set any we is trial we with in unnecessary we’re another one and we No, that entire runs the of and patient when runs the into a patients run a do GMP it, run. of good indication question, do Gil, not because that’s sure clinical GMP our particular between to with and variability treated there to material patients doing

And to so our because GMP manufacture be do what a of able to we material clinical cohort ability dosing can we within do trial. have the is for capacity, an entire

make freezer excited pretty do comparability there needed type we type material have we’re of would that do the kind put So we that. also any is and comparability of in we between be to support to or of Not could and the that to have we preclinical also regulatory a for material, left recharacterization any do filing. about that any needed only but analytical potentially that to keep analytical sure material over routines ability back go sure always make

Gil Blum

the on you Thank congrats and progress. for Great. our taking question

RA Session II

Gil. Thanks, Awesome.

Operator

you. Thank

from Eun with question. Please your proceed Yang next question line with the Our comes Jefferies.

Eun Yang

Thank regulatory you. couple end on a I clinical have we of by regarding and are of XXX this expecting update questions that the year.

be question. that’s the So with update? and by meeting So will to of you’re you year-end. come And requesting data engage end the going regulatory so before FDA out on highest with phase core AAV core question is, second high-dose the first the

an a you or meeting that the discussions from you update So Thank to you. next request possible could agency is would it year? for early waiting and potentially think meeting regulatory the have do you happen

RA Session II

hear your questions. it’s morning. great Good thank And and you you, to from for

So I’ll take these. of both

any the share in regulatory disclose it’s discussions So that year. we high-dose before to have would think that from feedback perspective, the likely agency of plan disclosure a here we I second particular we from any cohort half the would data

timing the perspective. that end is request the not from feedback year the The and of by have So a year. end cadence goal of by the is to the the meeting

submissions when meeting that they request the ensure to depending we be those it’s and or do putting here Those a we month them be meeting have is to COVID. bit the order So we’ve workload will to meetings next will because agency, those that, tried in meetings submissions. little of up What to know obviously, early we cases, grant so in feedback in can you a those on some the in with delayed.

granting a normal straightforward, receive similar those be going perspective, the meeting from from bit somewhat a approach year. period, the end in Europe, to a by in MHRA, feedback particularly take particularly from MHRA, get In time we’re with a U.S. And so of where in here here request we’re the put of those to the going a to GAN scientific meetings a EMA particularly to meeting able quite more perspective, perspective, efficiently. advice advice are a face-to-face to meetings you’re honest. been and And agencies little relatively have time with scientific them

an way to the certainly, in the the regulatory feedback So to have Street of the we’re that second that’s we here this hopefully, will in update our the that time that’s going by order end to interactions But year. approach. provide And half going-in of year. approach in

Eun Yang

quick Okay, I thank on have clarity. financials. question one the And you for the

material in you quarter, second So in other purchases. around and $XX R&D, million raw manufacturing have R&D

– they be quarter programs with run mean, from first would you. R&D rate? And the we normalized I that second of second to the the forward, second the rate? this assume second quarter are going advancing. more would the increases quarter, you quarter-over-quarter year, half from clinical all So R&D third Thank from increase should expect Or run

RA Session II

and additional you good some start really maybe provide I’ll color. question. Kamran, Really, want to

over have the to would confidence we discussed, half were our GMP those had that conducted support clinical that in multiple patients was a in again, high trial this and of in I here a campaigns collaboration be with high year, robust partners goal think material of particularly second our manufacturing the first at quality, being treat starts as number we’ve the in to And we effectively. quarter, had Catalent. of to degree able

development as have that expect way kind of perspective, in cadence a the the in XXXX. we of from will the large as be are ours moving programs IND/CTA as a of to With we portfolio be into of will programs year into as that that enabling running a number new kind – clinical are move programs well number development next currently the get into into studies clinical that as moving

some we And portfolio so with there consistency there, you additional will think that normalization. see level But of the I color. to have, and the provide Kamran, some certainly breadth will want of growth. some will be stop maybe you I

Kamran Alam

thanks and RA the Thanks, for Eun. question, Yes.

So clinical you portfolio, programs into of numerous incurred to clinical we trial our this ultimately, can as half down well. expect getting and second trial some in expenses continue in XXXX as see the initiation, additional year

Eun Yang

Okay. Thank you much. very

RA Session II

you. Thank

Operator

you. Thank

Prasad question. of Our next question with Raju from your line Blair. William with the comes proceed Please

Raju Prasad

in particularly XXX, of to a maybe the of opportunity Thanks is. question. identification that of scale-up kind and the related that how taking lot understand just for we of commercial questions patients market I how get big kind of want going, is kind are to

maybe scale another up? of kind building you just could have you you of that up So, if then number are the prevalent about patients the how talk of I looking identified at commercial got And and follow-up. kind

RA Session II

It’s a morning Raj. question really good and good

And particularly actually we so thinking are patient quite are we pragmatic, today. that about way identification, the being

Head Zolgensma our on for U.S. and the Chief Commercial the actually when Officer, of General joined our brought he Manager who we Zolgensma. Taysha, was led have only – not commercialization So, of he

on the well him, Payer program VP We Distribution, on who led program, program of Product Zolgensma. Marketing have who leadership who our the also of our led that also as that Zolgensma of of Marketing below brought Engagement in also VP team was Head on Zolgensma the our as effort the Head

previously about about. on. announced of have thing done which a foremost So not partnership, and first on was is important partnered to From first with only us. identification we we and continually they was it kind Invitae people foremost, that perspective, a to what exactly were are That bringing patient talking what that expanding was we knew the

life, also being a population know the particularly progresses what late-onset to around patient ex-U.S. recently that the prevalent onset quality death. late kind segments; GDX and in Early typically form progressive to decade but then compromised patients and presents of and to partnered teenage albeit have split early-XX population quality of is is a live identification to with disease it’s late-teens that kind into of we significant into progress GAN We around has this GAN fifth life early really doesn’t about more GAN. this And onset onset pretty of GAN years a And death their light. of impact, two of these the typically that typically tend

so And population. populations in the about those patients larger XX%, those where because prevalent between large and fairly is that’s to the GAN, split XX% build And GAN. the XX% we majority onset – progress being able the up the not to quickly really to XX%, are being early tend a late two population as onset

So, be when would of incidents these opportunity. small. about The here real relatively you incidence is think this, prevalent the this – a

U.S. And piece, all are to late haven’t the population patients. big. the we partnering around identified, with but somewhere or XX onset gene so are genotyped. the and the been talking DX going really And the so somewhere Foundation. – in out with are patients We actually they But around prevalent is quite or is this U.S. and XX or Europe, what be important is CMT I doing that’s think going

a So, it patients we all the way of And around are the currently X is is in with really And you U.S. type about the the have patients per would about be right their that that could there late births X,XXX even of patients, the we And Europe. But job type which is literature. through that working X%. literature in the think is of around or X,XXX X%, a incidence around CMT you or with XX% But two CMT number have in group that fully year. our actually want little population be CMT is one has seen of some then discussions they more to The and is we number think sites about fantastic onset about network and CMT that. the Foundation two disclosed mutation. confirmed done higher, of conservative. to validated U.S. is the use our that GAN population in goes GAN X%. CMTX the up population GAN the CMT, throughout that a a genotyping, way million in of are But bit We clinics. X% X,XXX for clinical now partnership

We it’s like higher and epidemiology estimates. we said, numbers, how this have with get the the actually the ultimately number – Europe closer in be conservative is the that But U.S. but seen about literature a calculate our that back helps. our lot is I X,XXX. gets Hopefully, in into Likely, double-digits. wanted to X,XXX Europe, probably to we to and to X,XXX,

Raju Prasad

get program to looking that you at on the forward? off Thanks. morning. Great. next kind Zolgensma And how that this I disease come coming we then look obviously, how panel with Danon wanted FDA as thoughts with at up just holds as month, some Rocket’s to have guys your of well panel seen are moving clinical

RA Session II

maybe Awesome. that want you take question? do to Suyash,

Suyash Prasad

Yes. Raju. for Thanks the Sure. question,

think, especially nonclinical looking and look the structured tissues on way the DRG finds thrombotic neurotoxicity areas. am I I clinical brain for in five goes. how it’s oncogenicity based MRI the forward front going and to to panel, findings. related then risks, integration yes, that toxicity, of on toxicity discussion microangiopathy looking panel and They to interesting. seeing FDA be The actually seeing the have the at specific

considerable looking of mitigated both us for So, by those these they them, five we given All if talking that issues, I thought and looking have to some some looking are have work. in and about, our against think to specifically listening learning. areas them, at we actually forward just are preclinical

example, we built also we DRGs signs DRG in nonclinical monitoring local but studies And you our tissues. inflammation. i.e. clinical we perspective, haven’t of For seen at of as trial appropriate to look now. preclinical hepatotoxicity well, the far, at design build thus into mitigations from the in And not all in things just looking NHP any

discussion in been an built platelet the at to have up to have that we microangiopathy. inflammation DRG how a about clinical clue for – And has been essentially, visit. issues the very in monitoring trial. it’s to – reflex we which a at which thrombotic with general is actually clinical monitor interesting periodically gives We in come with look look good – with early counts, testing plan looking just over We at each at the regulator acceptable of, regulators

nerve body, knee, the So the to specifically, reflexes And conduction period the studies thereafter. the and in six year first also at ankle, three-month baseline etcetera.

should the into hoping mechanism And also to should they issue serve, they it once risks trying progression being that rapid lot a in that. patients big thinking context, am be will included thought. again, I clinical being to and of are to that’s are who dosed. more because about not to some around are this demonstrating balance giving the happening. am a been hear not – hoping of go we the children and from And have benefits anything take hoping learn this or am we a more at in the issues towards minor I So, the communities that not to I what’s am trial that I of charter patient the for surprise us. preclude the of meeting expecting safety detail that in safety context have offer at look these considering they that the

RA Session II

on Suyash, field. obtained of plays because maybe you have want our going program the that I into just comment we this on just what’s some of GAN kind to NHP in data in of kind recent think the

Suyash Prasad

to gave eight looked approach. recently conducted re-dosed our of NHPs, reminder. these it’s in the that factor of specifically study our Yes, you. Sure. for and re-dose And yes, in But – of clinically GAN at these program, NHPs had another tissue. a actually we property. subsequent dose assessment, in Thank that we GAN the there we new good any neuronal took some NHP course, is or Alright. that part a study re-dosing spinal in as specific we meaningful weeks of those with focus, very of the carefully lots and dosing. And all one a that DRG toxicity doses. and And looked inflammation two signs received dose the received NHPs, cord of both and interest those And of on

took. So, evidence kind in samples the of any information whatsoever we no of of any

from in was clinic the reassuring our it’s for specifically perspective, and moment vector So, it us. is a the already at very

Raju Prasad

Great. Thanks.

RA Session II

Thanks Raju.

Operator

Thank you.

proceed of from Our Please with Zhong your the question Yun next line comes question. BTIG. with

Yun Zhong

Hi. Thanks taking very my questions. much for

to need GMX efficacy, the Do biomarker the followed how think on question long to any first for suggesting So, see patient you include please? to clinical substrate do data expect be And will reduction? signals you program. you

RA Session II

first and disclose Suyash to you. take Queens XXXX, maybe perspective, key And second. to the the in what will will – will around data aspects the Thank Good we safety are when take data XXXX morning. disclosures can will from a I second we be From the expecting take question maybe and disclosure would see of the well subsequent the enzyme kind and on. then kind into in that as But study year, will the providing two feedback clinical the of data first as measurements other have X/X be Phase of be this you question the be some moved of disclosing providing impact. that of markers HEXA CSF. two be on disclosures activity Suyash, second of from disease. we we around Those want be half you your second question we then will those half timing later additional around for the that will

Suyash Prasad

Sure. Thanks question. Yun, the for

the what’s GMX, I events. a think important dose question, with to normal it’s just what’s happen the course the of what’s of course, going events, after expected we patient cadence an

be be blood. in So, will the CSF data showing biomarker that is quite will we the correct and RA the levels HEXA in and

specifically GMX ganglioside asked reduction. You about

We are, change. a than HEXA guess bit longer the that is little that. My will take measuring of to course,

hope in clinical terms And transient a anticipate expression, the that much get so three cadence disclosure. events, of my also dosing. is is after of more weeks I if late will maybe patient, – – a about you that dose you think be there should And you improvement,

progress about months. some [indiscernible]. guess seeing three until And about months. I first start of take increase six guess dose, by the guess that be may I nice should month, my clinical wouldn’t longer, you then three treatment it maximal. the It would change months. should after hope be start signs stabilization, the that in activity. may even to see see So, seeing in HEXA be is three months initial it a by My is by the beginnings But you the will of to clinical

Yun Zhong

expression And the do have look of fall more just would clinical kind Okay. you on the mechanism target range on to that will or that see the then the gene the program, that point, on into hope of end range you Rett self-regulatory transiting syndrome to you rely the please? a technology

Suyash Prasad

this… Yes,

RA Session II

Another ahead good Go question ahead please. Suyash. – go

Suyash Prasad

Steve what the MECPX – that. What is you anything intent say I about there the in animal Well, see that try levels of answer Yun. know that everybody it – exactly do is I kind designed get none microRNA advisory a too little start degradation, physiological, question and a that of upper the way – just have much than lower, to And The Gray XXX%, had I MECPX level are good And it because But the more expression. asked for XXX% has will little is range of our of XXX%, XXX% It’s expression, have is some deterioration. they clinicians question, you XXX%, so but sites. conservative. They i.e., bit number XX% get when you normal, okay. studies, We we between run is limit? is lower our and and and what a Rett, we alright in XX% – keep what’s starting is of was XXX% is generally binding can need XXX%, bit of the we hit about you out. same the boards MECPX, levels to to miss a will a if being it’s the between jump really been

expression in MECPX to up of expression. look measure a we buy to can’t brain because course, you Now in the order of do at levels have that, to chart would and MECPX

wouldn’t vast except, in penicillins we MECPX get but ethically, possible, autopsy unfortunate technically and in course, biopsy clinical the of data wouldn’t in to die it’s cases. the able But that setting the expression in of be to be perform able to an measure So, that you would obviously take way. majority the

feedback so the is treatment. on And target be able to to physiological we to But relying be obtain the is are in very going particular which loop self-regulatory nicely. going clinical very, levels,

Yun Zhong

Great. Thank you.

RA Session II

Thank you.

Operator

Thank you.

next line Stanley. comes from question Ulz Please the of with proceed Our your with question. Mike Morgan

Mike Ulz

Thanks question. guys. taking the Hi for

a the on decide are the year. GMX study? multiple currently modifications there? make this do the sort the study doses you secondly, assuming you advance in results Thanks. Queens advance to material are get or for then in the single you material X/X you the to using need an to are program, U.S. But U.S. And you you that process study Just there, versus to any plan of use might give into planning positive you dose to later track update to Phase

RA Session II

Hi about with. Canadian I that U.S. material trial is second second exact process you Mike. material made will Suyash your for maybe the question, the the take we dosing. manufactured same the want produce Thanks the question. and talk question is study the same with for to But the in exact that clinical being to facility

material exact will product release with that testing. So, like-for-like same the same same analytics, the be same characterization,

is So, do then pathway start sure we we the that take are and pretty versus back why for do some change. having of type reason development around quickly that fortunate do a regulators have to to if that are make relatively able that. to remarkable result we And regulatory to that we process go and see to discussions

material you the the that So, that’s talk same to exact want – just question, original from maybe facility, your so, identical to dosing. about process. Suyash, same

Suyash Prasad

very a touched is on good this the wide about need significant that Sure. to get has don’t programs for And the therapeutic question, Thanks window have one Yes. that you thing of already Mike. improvement. GMX I the much i.e.,

will of the than this X%, that. about enzyme enough span based the by HEXA. When disease We have less that on that current forms the levels adult a dramatic say they i.e. infants show X.X% improvement. I would the to exists be are And you life result X% to for to that X% go more disease, than seeing activity actually in data normal up of have of

So, X%, improvement. then you that a are will be more dramatic hitting quite likely, if enough you to clinical give

improvement. a So, to you don’t results clinical in to get that much need level considerable

toxin can pharmacology, enzyme. On the you seen we enzyme our physiologically, safe super a And actually preclinical it’s the other express end, have in work. this and very

other you end. adverse And it the express So, no super can on there. are actually physiologically there consequences

So, we broad have a very therapeutic window.

high you systemic is Now dose dose to to it’s being total relatively gene therapies. give in some administered comparison context, low XX a intrathecally, VG given but a

to our we So, are XeXX we quite significant actually think likely that have dose. a with benefit

a will probably clinical in in go for and good benefit dose we dose that from biomarker the we with If room if and think more important indeed, perspective we data. ahead U.S. improvement. file Now there are from the on study just seeing that in XeXX perspective, XeXX is a the a

we VG. XeXX opportunity to higher go guess have the to go to. My would from if we We XeXX is need probably total absolutely a

any a it’s is doing to U.S. is and have the designed we of if bit we for from room improvement, So, we I learn I little fully possibility be absolutely that. the finalize The there to study finalized the haven’t think going the potential scoped yet, likely Canadian good U.S. we study that is that are for the not before XeXX study. to design to actually of But go XeXX dose. enough. But think fair

Mike Ulz

Great. Thank you.

RA Session II

Thanks Mike.

Operator

you. Thank

Our Kluska Fitzgerald. question. line with the last Please with your of comes Kristen proceed question from Cantor

Kristen Kluska

Thanks morning. much question. taking so good my for Hi,

the to the with specifically, the what GAN see in of gene the reported down you and therapy what could For including you guess, discuss progression? program, please Thank understandings brain were the validate some you. that MFMXX, help signals further disease light the especially strength in of would And correlation recent on and hope assessments I publication? MFMXX, is slowing Brain the beyond you muscle including that imaging,

RA Session II

morning. will to over Good Suyash, Kristen. turn Hi you. I it

of we shared, is I around just the some we acuity. think that probably data something visual have particularly recently best that

going endpoints meaningful is of endpoint. Suyash that extremely be to clinically to the then point on life other And and a end of Kristen particular patients such that discussed. quality touch some because that maybe think I it’s

Suyash Prasad

Kristen. data probably question, NIH a I XX wealth could a or There about spend good in this the XX talking is collected this. study And for remarkable. such really being minutes Thanks Sure. minutes of is

– is I seen have MFMXX, the we as INTEND which it for CHOP describe children. So, always older

shoulders the now this opposition, we and more the some snow get sit been response seen patients in have disease looking a high we that, like we wall. at called does and three have mentioned, strength, of muscle and there this what manner. drops at medium-high points with and vision proximal fingers LogMAR. have the chart. and with When and strength, LogMAR. year. a arms, And eight something by hips off at as on a central in showed research-focused visual And clear dose we clinically has a the LogMAR kind see distal got in points presented we medium letters of every Four progression. stabilization at domains bit is you stabilization and dose. have of medium, look RA low In decline dose the deemed GAN. And the forget specifically, And treated, and you read of clear rigorous you MFMXX acuity. strength of The seen clinically stabilization have toes. this data that is in This year we to within is significant a the medium, kids that difference conjunction And low disease be You to the meaningful. to

the GAN, have vision deteriorates children it’s clinical So, most over who significant, their effects. time. most And one of worrisome

that parents much way it to the words ability the the in same to fact their means that example. of stop ability communicate hear, about one loses being and the anything more for able think as worry moves than articulate they things to that so I because see child also

it’s data progresses deterioration when being patient And scale deck X.X have now, majority there slide going registered legally our blind. corporate see when need you you you the when deters see, hitting and are set, very you significant you treat when loss troubling a we that’s After actually you the about as our are apart of the about of one and vast visual over patients, lot is you So, glasses, LogMAR score is time nice what in from When a a X.X perspective. X.X, blindness. in family towards that halt about and from outlier decline.

of is So, stabilizes you acute it’s at where and then declining, level the out it similar to treat suddenly visual MFMXX the function.

duration have preserving you vision the significant are study. seen So, for Certainly, particular children. duration in this a of we in these visual preservation

So, vision is key.

to looking terms are of we stabilize, one those looking quite sensation going at guess neuropathy but improve that measure. other sensation. to is parameters My of or endpoints, is type that’s In and hard at it’s scores

confidence in true to will to strength, assessments the capacity highly, also improve that You are Carsten the already will you were MFM the also assessments mentioned the of looking etcetera. time respiratory And out. the some and with muscle stabilize. because they major earlier. the and strength. again at stabilizes I me of the think that stabilize, And these way once also correlated muscle walk the myometry I tell vital anticipate such brain ongoing that’s in other [indiscernible] is test, for forced stabilized guess the deterioration I will things team these say strength study as paper history natural My in And all muscle also alluded that highly

Now measures, doing in clinical a addition the tests well. we also study as in number the are to of

performing nerve we these is scans. are looking And MRI we performing too. vast will will the in to is have the I forward seen but at pan importantly, patients, out, conduction how the reflect are am electrophysiology, guess my biopsies also we in So, majority looking days seeing at there, i.e., looking studies what MFMXX.

Kristen Kluska

taking you for question. my Great. Thank

RA Session II

Thanks Kristen.

Operator

comments. concludes will to question-and-answer Ladies Thank for you. turn final the floor back session. Session that Mr. gentlemen, our I and any

RA Session II

progress we the we throughout the will this and for We forward this over to thanks, look on momentum Thank of year, ahead everyone, you, it end to you continue joining on turn Operator, and until the updated call year. building remainder keep will of today. operator, back you. to our the

Operator

Thank you. And this today’s concludes conference.

your disconnect at you lines may for time. You participation. Thank this your

Taysha Gene Therapies (TSHA) 16 Aug 212021 Q2 Earnings call transcript