TSHA - Earnings call transcript Q3 2021 | Taysha Gene Therapies, Inc.

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Operator

Welcome to the Taysha Gene Therapies Third Quarter 2021 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen-only mode.

Following management's prepared remarks; we will hold a brief question-and-answer session.

As a reminder, this call is being recorded today, November 10, 2021. I will now turn the call over to Dr. President Communications Vice Investor Senior Lee, of and Corporate Relations. Kimberly ahead. go Please

Kimberly Lee

you. to corporate results welcome morning, update third call. Thank and financial Taysha's Good quarter XXXX conference and

today, efficacy of President, the call copy forward-looking Medical Chief statements announcing a relating Please will and release Officer. XX, filings. note the Head Kamran and Session on After on expected Suyash that and Officer are include follow may to our for quarter our on time. and R&D; the statements Chief Earlier company's These commercial remarks, product me of Founder; Dr. trials including therapeutic the today's we available II, making website candidates. financial September Joining Taysha's product Alam, instructions CEO this of today's at our the clinical and Prasad, through release be press SEC RA press for and and Financial we potential candidates. Taysha investigational our question-and-answer safety will of XXXX. a statements session third conduct timing results ended results and issued call, that A formal is will and

conduct of are and intellectual results regarding as These related by relating timing opportunity facts necessary our well risks of forward-looking and support implied limitations expectations third to results, historical product actual alliances cause and Various results in materially as candidates operating also Taysha-XXX, statements and forward-looking to discovering manufacturing for strategic of may dependent patent growth activities. different property, future stated may and and from trials include upon continue development strategic alliances, Taysha's substantial matters and in not information. uncertainties parties, research to as to and requirements that our to Our or development plans. status and imposed third-party ability as Taysha's clinical studies for product relationships, regulatory or data statements. by obtain of owned pre-clinical funding are risks our patents discoveries, Taysha's candidates, regulatory to well approval the the programs, the such those protection other of and market those This or call controlled

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

RA Session II

for the I you, regulatory from Kim. CLNX, welcome everyone and a achievements Rett for Foundation an some and several our Southwestern our on exclusive disease for awareness Angelman of highlights leaders, will expected our milestones. Association with UT recent featuring GDX, upcoming increasing program a CLNX on discussions been Thank Charcot-Marie-Tooth key hosting conference as with and program investor Hereditary ginixonaneuropathy It for and programs, key results CLNX elaborate license quarter well busy has webinars financial construct, update and to corporate third quarter partnering Good the positive call. on as overviews obtaining with and and Neuropathy next-generation syndrome. collaborating review morning opinion

our stage results developments Southwestern were for exclusive pleased updates was CLNX announce dosed to In gene over a AAVX that our Advisor, is XEXX with safety on from program, the a will proof-of-concept I therapy Steven financial running expect data UT ever and an an currently this intrathecally, first-generation first trial Scientific to construct, option VG this, data, preliminary clinical clinical patient dosed Suyash from end replacement we invented UC Chief to the Following call respectively. Kamran total by Southwestern with Gray. pipeline including have turn intrinsically the October, Dr. the clinical to and year. by license and we of

further is in Southwestern generated and will that UT education, next-generation awareness, to XXXX. safety, stage manufacturability Hope, pivotal with first-generation Batten To disease. construct. efficiency program. clinical advance over have planned Construct collaborating construct be for approved are we the from human a there advocacy newborn by the patient to reference to provided support severe of a are a initiatives screening completed advanced a grant excited work year-end With packaging neurodegenerative trial and improved no disease treatments data promising proof-of-concept the storage Hope Currently, next-generation patient are with Batten potency, to for And design CLNX We construct to and anticipated this UT this provide to group. first-generation support lysosomal we Southwestern initiation develop leading using CLNX, with construct.

expect of by stage clinical end the syndrome. ginixonaneuropathy, programs including have With addition Rett the gangliosidosis, the CLNX and to program, of this CLNX GMX we five year,

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study. our in In end of and request patients data GAN, agency to we and requests for we clinical collectively ex-U.S. TSHA-XXX forward the data year. have submitting major years safety longitudinal ongoing years six in by agencies multiple regulatory to clinical submitted additional of efficacy a this of end-of-Phase September, For GAN, and XX-patient an up meeting look regulatory individual to to from

forward of consistency of dose endpoints, strength longitudinal to natural eight the There slowing look total data considered progression from by assessments, We robust disease including and to being be achieved across cohort functional data of from data the disease safety lower that where Dr. of multiple at the history the have the biopsies. has of meaningful cohorts MFMXX Bönnemann. scale, clinical and modification. in MFMXX NIH in for dose believe biomarker X.XxXXXX functional TSHA-XXX clinically a Carsten nerve high December, VG conducted confirmatory reporting vision and years would also we We continued similar with study been

modifying the plasma activity plasma in normalizes enzyme HEXA and would based the disease X% CSF of plasma express December enzyme HEXA for activity in the clinical is of data TSHA-XXX in the GMX one least clinical to HEXA and December ongoing vector For remain preliminary history, activity the subunits data bicistronic natural to history. CSF TSHA-XXX, history, enzyme on the in of survival HEXA gangliosidosis plasma anticipate phenotype be X% first enzyme the GMX in significantly We to gangliosidosis. the activity to in which the study. We ratio. levels X% safety and track the considered of and endogenous We year. in at enzyme data, natural in believe improves clinic and preliminary one this Based HEXA safety clinical report in Canadian designed from on on

demonstrated and preclinical support in of medical was disease profile, data Regarding Due knockout U.S. to intrathecally GMX currently well-tolerated and need, to delivered the the registration. need mice. the of global unmet for we're safe TSHA-XXX severity safety assessing study

parallel, total including December. clinical XXXX, safety to preliminary with generated For pivotal first-generation data program, to intrathecally history VG a construct CLNX by reference patient in in second-generation trial data first-generation at in expect we our XEXX anticipate year-end finalize dosed the and In to of CLNX clinical the the we first initiate clinical the construct with for construct. the design be planned by data

suggesting levels an open-IND intrathecal CTA active mice For CLNX, and adverse program enzyme for to in clinical preliminary half first supraphysiological We demonstrated been of the of the has CLNX TSHA-XXX clinical administration models, the filing therapeutic TSHA-XXX-treated preclinical that an associated TSHA-XXX data tolerated XXXX. was data by activity well no PPTX window and and wide currently safety with enzyme to plan a expect clinical PPTX the trial in report end mice year following model. effects, submitted. this additional initiate Preclinical safe the dosing. demonstrated knockout and In for has of

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regulatory go provide forward update you Let look the our will programs, throughout our now across milestones much our operational in with more strong by we'll a quarter, detailed regulatory believe over our the Suyash We this to I year. me but financial us to of And achieve and to balance please Suyash, this provides and progress conclude our to and remainder potential accomplished a we call across we sheet our TSHA-XXX execution approval ahead. our for to have development on initiatives. that continued R&D ginixonaneuropathy. update and the saying value-generating on strategies. numerous importantly, flexibility turn more execute on have

Suyash Prasad

Thanks, RA.

as across programs highly unmet of well strengthen preclinical multiple We year our approaches, needs and monogenic of with advance across as continue the to to end several anticipating approaches therapeutic At data are readouts CNS. we high our pipeline address clinical our lead programs. of clinical complimentary the diseases the

ginixonaneuropathy our our partners Carsten to expect me we December, total Let collaborators and high TSHA-XXX, of These clinical theoretical the with the report clinical NINDS leadership data cohort MFMXX the most VG. program the data under or functional study, [ph] start are of from GAN. In for dose and X.XxXXXX Bönneman. by treatment advanced of of safety generated

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received appearance And clinical up which TSHA-XXX the is this of January known of submitted journal publication signs of or no regards have to by levered scientific GAN, from We data no also we in sensory complication the peer adverse and disease safety in a with safety histopathological events, of end years advice near that in additional a reduction persistent for a supporting anticipate and elevation to recall by drug-related serious the XXXX. no regulatory symptoms. studies submitting date the meeting changes the In six improved year. to ganglia, gangliosidosis ex-US future. agency requests scientific safety using no inflammation, and preliminary the Regarding agencies data transaminases. We of major root dose demonstrates September, of reviewed preclinical of sudden subacute regulatory multiple acute clinical we anticipate

we the few conditional effects have we believe material. use clinical dose think gene file for for be trial, hand. Alternatively, And the for given as compatibility the as forward long-term between in grade least would pathway current we data have support option datasets new the documents able In to approval we additional FDA to likely the neurodegenerative approval could regulatory Europe, finalized on likely a the we In to patients We therapies request interactions. the us and commercial recently demonstrate providing hand, extensive or we FDA the United the a view the we filing. As and that the compatibility grade clinical have published our a diseases current lastly, most request, BLA/MAA approval. protocol potential possible to view the commercial on plan clinical dataset to meantime, in scenarios guidance three and the GAN the may upon about perform which following States, scenario. we look with with to the initiated updates material

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approval continue trial assessing disease the to regulatory with our regulatory and HEXA we study. severity the are and and be plasma and CSF anticipate our need, preclinical considered plan well the plasma are enzyme to data in of safety in treatment demonstrated in of least enzyme clinical at path to activity data the well intrathecal modifying. enzyme Moving medical report currently mice. from demonstrate GMX U.S. December. enrollment program activity, on we the disease delivery GMX patient in activity a of Screening the Canadian unmet clinical TSHA-XXX for to knockout was as HEXA of TSHA-XXX progressing gangliosidosis, agencies. data, that X% study need Due to to in safe correlation history for preliminary tolerated and natural Based a between HEXA phenotype levels filing you we the support fastest Recall evaluating and

granted As recently from the designation from a reminder, Commission both TSHA-XXX has orphan TSHA-XXX more GMX from the the has also rare for gangliosidosis. European been FDA. FDA, received of pediatric treatments disease the designation drug and

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Advisory selection. our groups design, We focus who inform insights and Board and the clinical also from helps reviewed endpoint caregiver therapeutic study Scientific priorities

continue the our to to We explore pathway approval fastest program. for CLNX

initiate a submitted filing plan by a and X/X Phase year-end. CTA to trial have We

for TSHA-XXX PPTX based to there degree in symptomatology what improved Dr. biomarker clinical be international to regulate University of design our requirements a X% Medical the treat cell-by-cell exactly an for without Neul, adverse natural detailed our MECPX clinical transgene is the highlighting and level rat Gray does, that adult that cell-by-cell neurodevelopmental platform onset genotype disorders to syndrome is X% Dr. And Rett seen disease. first provided Rett based positive Steven We an patients. the trial increase would hosted ensuring for the of to at considerations XXXX, underlying Center in genetic an outcome basis and half regulated of range history effectively a we effects. safely Vanderbilt causing considered overview basis expert of measures novel expect expression in and the on to program. undue the miRARE a including in In Investor the X.X% selection. activity biomarker from that's the on expression X% expression on of gene report PPTX Day noted data from September, Jeffrey on

Importantly in was preclinical not side myc-tagged death our dose clinical our the mice supporting We early MECPX regulatory TSHA-XXX positive effects demonstrating preclinical IND-enabled expression. animal with models strategy, behavioral intrathecal type did in associated not on wild of cause development appropriate downregulation feedback and package recent reviewed selections. protein adverse current

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of approach replacement neurodevelopmental Dr. no UT of with on gene treat replacement we syndrome Our the Southwestern Philpot the Journal our disorder Clinical this unsilence to Recent paternal for one significant both data the to syndrome phenotypes vectorized preclinical designed the presented the the Angelman of Butler safe Day Insight UBEXA motor focused isoforms seizure highly our to gene UBEXA by UBEXA are Investor long presented three potentially most Ryan short replacement replacing world Dr. by silence behavior in the the further two-pronged discovery mouse recent publication targeting in concept as of detailed of gene strategy entire approved endogenous data transcript approach and ratios the and highlighted allows where of of encouraging Ben study Taysha treatments. in UNC key strategies These support treatments models outcomes, Investigation AAV-mediated Angelman how responsible knockdown copy as proof mediated approach UBEXA of gene. gene regions recapitulates of RNA leading syndrome. the antisense importantly and and effective syndrome. a further brain, Angelman for target UBEXA of Angelman syndrome. to the Angelman a improvements in leader therapy isoform in preclinical to treatment positioning and of Both in population of learning, promising

Kamran? we you morning, fronts both our progress the this financial updates over you forward With heard on turn development that, look review Kamran to regulatory results. to way. to call I providing the our along and As will to and programs continue

Kamran Alam

our Suyash. in Form This can details of which the aspects discuss our quarter be you, will key More shortly. will morning, Thank financial third XX-Q, SEC be filed I with results. found XXXX

to fees clinical other million. $X.X September $X.X $X.X As million September months attributable compared by XXXX, material primarily expenses research XXXX, professional The to advocacy communication, $XX.X cGMP million our The partially as in related consulting months offset the $XX personnel Net million trial $X.XX ended $X.X of non-cash raw $XX.X employee September activities, legal, XX, the investor includes release million of today, activities. months $X.X toxicology million accounting, was months and $XX.X included studies. clinical million September million which increase ended and insurance, ended of million indicated relations, an million, to for September which of licensing the ended XXXX. months months was stock-based XX, XX, share fees $XX.X research mainly by third-party share million, an recruiting, per a the XXXX. $X.XX September were compared XX, CRO loss and of press to for increase XXXX, was million million stock-based of included market three per which and decrease an of primarily patient to XX, ended of three a Southwestern. incremental and $XX.X $XX.X included or research, million in and for increase produced for which loss approximately three This development studies, was manufacturing, compensation batches compensation, expenses non-cash three UT the for There in compensation. million a were There G&A in regulatory increase three expenses purchases, incurred $XX.X XX, million expenses a was of in or Catalent in compared GLP of expense, and to development attributable $X.X manufacturing for R&D $X.X three was increase and compensation net $X.X XXXX. for ended expenses,

million September that, Taysha of equivalent. to had and RA. in hand I XXXX, cash will cash XX, call the And $XXX.X back As with

Suyash Prasad

some for reason. RA if has off dropped is Suyash here. I This wonder

RA Session II

Suyash. Hey, apologies. My

Suyash Prasad

Oh, Go my ahead, apologies. RA.

RA Session II

Thank on talking My was I mute. you. apologies.

So joining I call everybody want to today. thank for the

you months. with success over share to the our several are past We pleased

pipeline upcoming on ahead, advancing milestones. Looking anticipated and our focus key on our executing will expeditiously continue we

gangliosidosis. highest we As anticipate for construct in December, in our and a our HEXA enzyme Phase and the TSHA-XXX activity dose CLNX safety we first-generation from plasma for giant GMX clinical in data study reminder, TSHA-XXX Phase December, data and cohort preliminary preliminary X/X neuropathy; program. our the in X/X axonal data CSF from anticipate in Also safety from

disease. CLNX we by board, dedication syndrome. a our the advisory session. continued now mission our scientific Directors, day curative to expect begin advocates our I therapies monogenic motivation Operator? to the every develop and operator like to support eradicate of gene ask and patients give trial Rett Lastly, remain in to X/X of initiate would the and employees, thanks will special our Q&A Board to Taysha CNS collaborators, and continue who devastating disease and Phase year-end, to I

Operator

Thank you. [Operator Instructions].

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

Joon Lee

Hi, and congrats on impressive accomplishment period time. thanks for short in taking the of our a questions such

that with us if you may submit Canadian where would like approval you happened follow-up? data most And to for from existing you have be historic something be For have to and so, able the implying amenable and jurisdiction GMX site. this give what do be proxy seem the some this, think to you a can I

RA Session II

Good morning, you to Joon. over thank Suyash then it question. And his for pass the start I'll Maybe and provide I'll to thoughts.

clinical a coming have a registration ultimately IND open is current perspective, is to the U.S. you to over world. sense this from So issue. and all GMX a the clinical clinical not is is the that study literally study a on global need an endpoint plan, then based in FDA's on a in And an a a robust supporting from again, From clinical development supports should that the be registration, a in are the robust good good good history, trial robust data natural there taking a place BLA, -- trial. Canada, where necessarily file all guidance, patients where

the patients and disease U.S., need I'll full may over this. in or one how there's to of to certainly, the actually the and spectrum. this the clinical we meaningful just disease meaningful program disease, be multiple feel is from based But so severity unmet you and to trial rare two examples need enrolling; on medical of well a couple across may do a for there's the turn to the the U.S. import provide And not of it dosed. today the to examples -- Suyash of necessarily

to over Suyash it provide turn to there, thoughts. stop I'll So his

Suyash Prasad

are the thanks other our strategy of meetings And meetings multiple we've six question, Yes, ongoing nine four -- several through these four agencies. past regulatory programs. Joon. for to RA, yes, had talking and we're ex-U.S. portfolio months, thanks, and an And on U.S. the months regulatory In across with the basis.

right a we're pathway time getting real on information approval. lot approach to the So really of for

going As GMX RA There's of of able of the us countries, file GMX IND has as the Canada, we've already about large patients there's file are patients have opposed study. then perhaps tell it COVID. essentially, yes, actually, so actually, are RA Canadian for And a study. as to open said, identify other principally could we've screened talking patients been we initially we've been just global the out Because from with But and how the pleased, things to delays U.S. very well fact, large ex-U.S. numbers that that number says been a we from is there. in data relates to and some

there I is patients, Canada what to dosing. for are felt could send them U.S. we So actually if

options So there's here. multiple

couple in more In was much followed focus terms Europe and examples, I've later. U.S. of a worked our on initially by specific environment on the previously, particular where

mind recollection, And happened the springs program But why U.S. where filing study several in that's think one prior I to the in Europe think I the starts examples true. Brineura from to are ex-U.S. happened. this the has the my CLNX was then one there

clinical in we the value on to U.S. Canada, things going continue and at IND continuing focus time in point, still an we gathering we'll are for some an options. open to data in Canada. enrollment attention in but yes, GMX well Like So this, decided our initiate

Joon Lee

Great.

the FDA And data GAN, the six, data. a used worth data, last for Are question, have of to study GMP satisfy undergo with the in materials second if very TSHA-XXX Thank existing would need in approval they do same submit producing investigational be requirements, are you're the equivalent strong and commercialize to the forward Looking that facilities? what to which years' your to or materials are And for eight question the able as in in they different, and process and you QA you. you December. data? GMP

RA Session II

for Joon by question the question. Thanks the Great way.

materials. we to the that from a secure early when stage the the manufacturing of one platform to do essentially, can was program and make we materials to So in that brought on clinical comparability the commercial support we like-for-like things decided grade sure

filing partner literally was like-for-like BLA do what CDMO run same and do material, clinical and commercial original like-for-like and to scaled to go in manufacture partner which the will the do manufactured in we've the decided BLA So grade that, that validation to just into ultimately producing commercialization. a the to a support support the decided order grade is material up. What to process, with it we've

it's likes updated cell for process some same manufacturing the the therapy Literally, for that the same filtration. So recent same of for GMP line. It's developments to FDA the a gene see. purification

of that's nothing normal. So the out

support should you and add? strongly that product, anything feel a ultimately stop we comparability panel Suyash, supporting current sameness So do I'll there. current like-for-like our a have dataset argument. our to

Suyash Prasad

over ago at contaminants very the as learnings that I in the on only spend also of terms product really, think GAN add program bring collected well. those into for that ensuring the process. the to and the team characterize we of we a meaningful energy thing that two part, ratios. commercialized example time the early in manufacturing bring of were weeks able and through drug terms who's actually manufacture through very lot We drug I'll the drug will clinically, manufacture are CDMO learnings. where our a -- And to captured there's real We

So about Fred and processes of through people were at and all Officer, week Mish going our facility all details the ensuring that a Technical team possible. a it's full as Gerhart, our through and things Head absolutely pristine Chief Regulatory the XX the Porter, looking of as spent

that material clinical the to forward that to going used in confident studies going equivalent in what very we're material to using program feel absolutely GAN the going is clinical be commercially. we the the be So --

very approach with So, we're the comfortable yes. here. but question Joon, Great

RA Session II

to would that have add we thing material grade commercial is that, I the in only a to second available plan year. next filing half support of The BLA the

Joon Lee

to thanks Got it. Well, data you. December, the the Thank all answers. for looking in forward

RA Session II

Thanks, Thanks. Joon.

Operator

Thank you.

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

Gil Blum

a of the follow-up taking previous thank questions. on a for and you discussion. morning Good our bit It's

bridging will is I make kind? So that would be actually different each expect used of your a it the program. right. you any programs Do mean the using they're makes guys the you still looking commercially using study be in for translatable a variance across across are platform, it considering guys this your sense production to that method but genes now, conceptual AAVX FDA

GAN, initial it commercial So that it you into headways with you Thank could you seems really have are you kind products. it for you. CLNX, It long the have to for for transfer have could looking could GMX. make studies hopefully and of

RA Session II

had on is morning, of discussions that our is of that commercial some six by worth in-house basically I high mean and about of kind collectively Thanks the chime What to safety say XX efficacy five Gil. when what I'll for outlier. -- to Suyash years we process. years of platform was data really with good Hey, and GAN then product start a Maybe kind robust an is produced recent essentially of approach. somewhat quality with by data of in And brought I question. allow I'll would regulators this it robust program this the a

do the we grade And the fastest was to had focus the original that pathway why manufactured our decided manufacturing is we to exclusively ultimately to this the so we grade support will sure that material anything. change on clinical not partner the reason make what BLA. to commercial go material, And wanted which into basically to approval

its So GAN is side. off by somewhat

for Now I the think absolutely you're rest the of portfolio, right.

product product In is necessarily absolutely same line, the same it's Our the a the cell product. but to and essentially the process, cases, same not been, there's approach bio has downstream always process, this same some reactors. same platform the upstream purification, individual variability,

-- interactions platform. kind And strategy essentially, Suyash and competent gives our this this we're if one consistency there of regulatory around programs. value. there's notion had talk each of regulatory some a stop around with interactions. this of It's I'll and And we've fortunate about there's discussions that our let recent So platform our really actions U.S. or around understanding regulatory working. both actually ex-U.S., our nine strategy with us how of deep augment to is authorities our pretty multiple because in regulatory it the

to So context. in chime and Suyash, maybe provide some you want

Suyash Prasad

came the GAN RA Yes. purity, comfortable Officer in little hand for question, relate of yes, a wasn't parts is regulatory really the I'll thanks job in is to that GAN Gill. the Thanks, very And The add how because Technology once characterizing our I the our trials say, And does earlier Thanks. the We outlier, again, quite that. of very is And CMC. pristine who for right. an so and products. hands our having a color a we're three bit RA. weeks the every couple Porter, To team are the into somewhat, regulatory CDMO I the discussions, clinical it to Chief we Fred which regulation ago. up and as the adapt topics feel appropriate. up visited mention think have of come of with a interaction wonderful that characterization, the keep we interactions, this quality, really the that And to topics coming in some these three CMC And

the And to about third this accepted on and How a topic bridging topic assays Friday So and They three is we last the progressing? approach one and all topic you to second Fred all our and are those was in approach studies studies – stage very we have said, of nice what regulator. programs, look the, do? are the specific meetings very have do talks studies bridging and by The we up is came potency of assays. potency just meeting and what regulation fine. topics. that of sounds bridging our well you very type need the at a is planning how

a Just majority right as programs Once possible. methods, outlier, as we our wiped material pivotal commercial proposed can. early And we programs. appropriate. vast for the as we the as you've by but again, grade when have that absolutely do when to time follow is an bit And parts, to the majority GAN of up you getting hard for is study. it And again, try the We're the know CMC of once CTA. definitely ready, vast what thing of successful the our of you we

in our time sure point, a to aspiration just before really For that preclinical a when start part the want at go from any product much perspective. clinical make actual most and CMC all, that's IND-enabling it we smoother does regulatory the we grade ideally that's have study the whole have we to process commercial study makes that early at

Gil Blum

seeing a other? than better Thank program. you. there very GMX quick a the this on question or differences between measured CSF you're Thank high-level question. one, the Is a Maybe on say complete any different you and for scientific other answer of course than guarantee

RA Session II

will So, over a Suyash. I'll and Gil. turn And great It's start maybe to it it question.

history; natural I think the natural off well actually gangliosidosis characterized. GMX is of for based history pretty

of activity enzyme patient most the patient known from a disease enzyme at for taking early hundred the years. been They around in over this essential has of have correlates enzyme look half percent, a taking extend the disease, out juvenile an And a X.X% mid-teen a have to the essentially onset is knockouts. this activity mid-teens. a from We disease, to plasma, three. And from X.X%, and these onset you typically activity. infantile X.X% level are that in to that when you of in and death an or survival When the the HEXA to infantile severe a the be patient form disease is the form just that just to the And patient goes let to X.X% specific. me actually come that patients

X% Just getting patient to a to X%.

an from plasma. patient. an go normalizes now You that lifespan it to patient the And is just And adult to onset again this infantile X%. onset X% in

in we But, wanted HEXA plasma progression. go into have And make sure to that depth. a to levels to activity HEXA more let why Suyash that. probably are you'll plasma that's benchmark correlate disease the different that but so most certainly the bit measures well-known I'll And versus in the we of CSF. reason little of

Suyash Prasad

a to RA right. many, Thanks, of expectations been known there's William RA. a about late is identified to is was by understand comes historically; HEXA screening gangliosidosis Gil, it's because really been quite question, was important going enzyme the we're perspective. see in XXXXs is and this in perceptive what from that XXXX Yes. off There disease many a lot think that's done Tao programs. The the ophthalmologist. GMX HEXA described I

see we of good at also want the plasma look we HEXA transduce And in trying activity. a only believe ensure we that should to in CSF really plasma. we to So we levels to levels, Having said to the than a in simply brain HEXA that, we're if look the elevation the brain what's have plasma also understanding little levels because reflect happening an CSF. will at more wanted the actually not cells, of that us

year. we'll that's data the and we've both the of So sharing days towards on be what end accounted these

X% that patients the some Now RA but hit also in those generally once adult clinical lifespan. are phenotype, disorder, GMX correct they we the with serum enzyme of are terms deficits There normal of levels haven't is in cognitive and movement quite gangliosidosis.

So if for infantile level clinical phenotype. than anticipate over HEXA we an we X.XX% X%, the the then from will less modify that to change dramatically that

So that's our bar.

presenting HEXA. but I end and we'll CSF be plasma versus on a we've levels in be actually, nicely see within we're maybe less as as HEXA CSF, levels got terms say, But my working the year. of assuming CSF actually towards CSF the a HEXA; both what outdated In the of less. little lower plasma of the preventive very than -- might the plasma the that may well, little and we HEXA bit levels levels guess X% maybe It's

Operator

Thank you.

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

Laura Chico

very Thanks small ones. Hey, guys. just for good morning, I much questions. taking the have two

base just if the regions the earlier could is you assuming a one, that any little have really And now. trying just on in XXX a then assumption that Thank So guess remaining mentioned the impact kind released understand, after or better commercial might kind XXX Last little bit I'm timing January XXX. meeting? just the grade when first more perhaps half related our there base ex-U.S. perceived I guys. like on issues I I commentary. second sure with material U.S. and have is case, headwinds about make we are there? XXX. sounds think timing of you just to for to working estimates the discuss case program, you the I regulatory path wanted be missed to right we just the understand should for U.S. more I on Apologies could clarity RA, the would wanted to that. bit that of It

RA Session II

question. then it's great questions, it And strategy. No, over to I'll you I'll a about Suyash the tackle Maybe -- Laura. thank and first your regulatory turn talk first our to

now, manufacturing that best programs. actually the manufacturability actually product ginixonaneuropathy. producing that, of product. We're we that actually would fortunate; commercial second of run the in and grade did foresee a of Right the actually of a it's availability material we small around our So for any that half don't limit of headwinds internally of the year. one scale And actually

a that But best such portfolio, it and across fortunate at data when And programs. reference to we look the have able be certainly, portfolio our having that's in hand, to, scale. one a so pretty to large of it's actually our we're have luxury producing to small to

commercial our to So excited we're about is first be pretty this that going that being campaign.

actually we that. foresee So headwinds any don't on

second in available about would you think start reiterate material we grade I strategy same. the is timing of XXXX. the an guidance think When that half the of to having So commercial from approvability still perspective,

issued FDA this checks essentially guidance in program this the boxes the draft of that think the all I were in out laid year. that January

have patient six of We longitudinal data. years individual

response. We have dose

of XX-years efficacy, endpoints. and We have patient multiple collective safety

other endpoints publication MFMXX, have biopsy endpoints acuity. here endpoints we'll number the data. in out And in comes of functional functional around that be about near-term. were that visual collected the not we that talking also But only a have We

So the are this high two its three the at way we is essentially, scenarios in think U.S., that we're probability. of looking those

Again, to the literally strategy from changing support FDA is anything. BLA we're is changing in commercial essentially going be the not like-for-like first not to filing, grade to analytical anything. The and really the material material. confirming going And We're material our essentially clinical using pointing comparability around this grade the guidance. on

could really we that nothing really scale. than there's So point to other

natural history there's could come patients we XX like the few Dr. in dose those have patients. back to study. to a at fortunate that you in for BLA, We plus natural by reported that They now support say we'd more a being the Bönnemann. end currently patients patients apparently of natural on history BLA. over of NIH have would identified year approximately XXXX end the collaborator are so XX And that robust run history a and We're Carsten now study study our

study perform so be patients quickly. more two would three from to to patients something be be sort to comparability to we some needed to to of if that able able And clinical we treat us do roll over would that relatively for

to the difference that analytical just doing of a And do end some so BLA the be support filing would clinical we comparability a an about XXXX months would needing comparability that difference. six think or between at

right. BLA itself, probably So to that mid-XXXX. push by filing would a Europe probably is all

just is medicine when Maybe, to there. available strategy be pathway And to conditional and our get regulators Suyash, going the I'll ex-U.S. currently data those pause what with is to and comment to back. just support. that we the responses approval, so us regulatory Europe, approval around is conditional and conditional will the the want meet that you the on are around boxes on going innovative the the the pathway wide really timing Year our New in checks all approval TSHA-XXX discussion issued open that early based guidance that's EMA in

Suyash Prasad

great just response some match come, the package data dose high Yes, so GAN GAN yet Laura, as a race, of medium and got of operational clear data and durability, dose trying medium of to safety I program. the give we've the we're for already to low, doses, great mentioned on disease efficacy. will at long-term color, do. this of We've stabilization high to And what just the bit aspects a the

and feeling regulators. And so discussions we're really with our confident good about

the One is challenges very, is just very of frankly busy. regulator the practical that

busy. out our to to In really actually agency meeting going We're you to look, fact month, us in we're looking said, the January. this we're push regulation question having XXth forward to and have but hey, regulator so really contacted

a on program, is just but happens. very that different that this rarely it So

agencies how it a moment, the sense generally And at of us gives just busy a with of whole the stuff. so are bunch COVID

So meeting but getting not for months, down pike. in for actually we're three, meetings, requests the four, five putting the

we're an say, also to discussions discussions. already anticipate focus with is And touched very plan thoughts that meeting for with and that's data of thereafter. out CMC little I we for; think January, especially make process, probably challenge something separate we on situation I've some want on explain So first likelihood it's we bit our that the we the really got how to operational got on timing we'll that meetings shortly partly our have sure CMC before we'll cadence our with the clinical is the of The frankly CMC agencies, well. a may those subsequent more this

some about talking discussions. the point I'll was So we're this of agencies planning final the and discussions all or I at in one two the the for days. separate right, for of CMC and clinical past length And make few

For data we've and this clear efficacy and got We talk dose length. at GAN, show about the efficacy we great stabilization, disease response. data,

It's fact data. worth that and me Head that's of One anything when as on regulatory the safety discussions just more BLA have program. so data, actually much what nice focus that for very years' this of comes closer the safety we to regulators focus duration in a safety And going then R&D into years want things to is the than we emphasize on data got of it filing. because with up I the of

a regulator to can have we XXXX. this turns usually But So and I have were dosed need you for year before study around and another the file. you hey, patients year, six in months who always or says,

we worth microangiopathy. that's there no thrombotic safety safety data, inflammation. of will longer-term, be appreciated any events. years' -- change know, all, serious liver or the recently. bucket AAV seven are with patients safety think around really issues. six be been no I of up nice really There's just So of of evidence regulators, no the length much of loss by because neuronal data. adverse some which drug-related And clinical There's no or in as very There's have I which very methods show very the to you gene the think at have over discussed minimal inflammatory brain issues -- will we therapy It a evidence

discussions. emphasize this long-term will good So that data addition which for I program, to these I we safety have to some think you efficacy in us just stead regulatory the want data, ones to we have really in stand nice

about So go we the Year. forward look to in telling how New you early those

Operator

please you. would Thank to Thank We much. to ask question. so everyone like just you one remind

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

Q –Elizabeth Webster

taking Hey, for good and thanks our for morning on question. This guys Salveen. Elizabeth is

just next the towards readouts disclosure, two several from given differences venue the construct the quickly could into what disclosure And data second if upon you maybe the those and us data Thank specific between patients, then and potential you, just year. you touched take. us, then and first the December be the have for And would on So between CLNX level molecular two? program. And expected properties the question or then but could the one different remind structural first just on next-generation touching on you format or

RA Session II

Good Thank the you Elizabeth. morning. question. Hey, for

first of your So I'll provide some question. I'll question allow Suyash insights the second take and to

the key and first the next-generation for and the construct CLNX. construct differences first-generation construct around question the between second-generation On the

the key that next make make the to haven't to manufacturability the We which that previously scale molecular some efficiently actually ITRs therapy those more to package in are as allow made know well changes more start weeks. on the the that do construct our once increase and we to we've can the improve upon make we to order design into few manufacturing. yields, vector We it here we as and changes of construct the large will gene are. that across sequence more happen get on potent, safe, in it is disclosed based will actually there plan differences what yet finalization, What portfolio, disclose

the collaborators history be clinical our same previously reference changes going concept some that of to out applying being VG. We're the on were patient data is that program. feel of to intrathecally we've constructs has from based to able just this dosed of coming We would be XEXX So those from that's we pretty at to UT made running. and the still dosed patient strongly They UT at total changes Southwestern. two our of proof are second and proof at third total been patient And that be XEXX, Southwestern patients. currently dose concept in VG our generated partners December. intrathecally, the One dosed trial been at currently has that

gene few of is made what be that in here. therapy improve so order we've I'll here changes multiple should and the happy once pretty We'll next which completed, construct weeks that And that. some is aspects in say of to design we're confident the share of to happen the

to activity for far -- data for of preliminary of giant the this in data end program HEXA as your and our the total by of process V second GMX our this year, our year. guidance for As question confirming disclosure, the X.X enzyme XX data around which high really is clinical is the dose our today is VG the CLNX of the cohort, end around athermal neuropathy and by CSF end by year, from this the plasma availability program

sense played to the you're of in drumbeat this as readouts like have kind is a of where move and -- we data we XXXX, starts out playing As absolutely the The exactly out of fortunate into kind how program right. would it portfolio to constant we're portfolio you'll updates mature.

the happen for safety, enzyme first be year. plasma, in year. to around of in half regulatory update an be and clinical well be update program, clinical the our functional There'll the feedback as that will manufacturing CLNX ultimately update approval that safety. around well comes as rapid support that on said, That'll as update in ginixonaneuropathy be CLNX as proactively well middle across come as again as and a next GMX CSF with of activity, There'll there'll in most of be a happen an And hope on we next next we've that'll the our and assessments for will what for as year. in, path So PPTX first which in as our the then -- all progress front. they'll half also program likely an constant

data, see constant drumbeat in you'll to I of both safety high So starting year, this efficacy actually quality think out the this clinical of and December foreseeable going and future. just

the the that else. large us going to not understand only our available patient plan Rett first our essentially on using data or have people fact generate and we think all loop any are because vivo, syndrome Rett to gene within the the cell-by-cell glimpses I of is but type support typically basis at exogenous the next of And also the controlling we year. of body. self-contained Lastly, in basically, to most construct, of of creation feedback anything that MECPX endogenous not population, value that program a the is in This syndrome, hijacking of the expression end

that just preliminary we've excited to as quality tox our we the some were be high well that again, so in some of pharmacology gotten NHP data. going is data, studies GLP new data as about And

as the into updates provide updates we and Year enrollment. to as get so providing And on on New that continue we'll well

think you kind about how of data readouts. that's So could

on high paper. that'll presenting also soon. We'll with and plan soon presentations I be here larger number and are papers the journals, research publishing those conferences. we a quality Street as touches tell are accepted that at published But starting would -- the will as definitive final be We ginixonaneuropathy, of hopefully, you are data and collaborators be And putting those some updating the relatively accepted. on where our of their

Operator

Thank you.

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

Mike Ulz

forward. you're the dose the going taking on data for a Maybe December GAN, how thanks XXX upcoming about talk you in guys, question question. Hey, highest in the about around for can thinking the dose. Maybe just stuff

continued in that For example, highest of sort dose in the optimal you stability, if what dose? mean of you see for the does Thanks. terms

RA Session II

Suyash, Suyash. I'll question? morning, to question. that Hey, over to and good turn Mike, take you want great do it

Suyash Prasad

as dose response as the a got Sure. three previously. already groups across -- nice we've you're shared that dose we've Yes, we've aware, so already

with dose X.XEXX disease and dose, was medium really X.XEXX, So which stabilization. X.XEXX dose the the low total the the low dose, the high VG the a medium more showed safety

high of points show degree of meaningful. those MFMXX the going both with decline dose ongoing doses. degree that at of guess the So that My improvement was to dose stabilization, that least is year which is clinically on is halted the per eight

As is in deemed we change. change meaningful clinically MFMXX know, a X-point be to a

translates meaningful we and is disease mutation we can patients already with on on mutation our have many heard most year, them the partnership meaningful neuropathy a per four patients years, years, that And ago, covered. And fact where or this press XX-points panels. that's on for we higher we probably be the and patients to do thing families. treat So if GeneDX, three they're really families. you to the we we when as And the earlier, of hereditary XX-points screening over level functioning, now which X-points for at GAN these two for these very over identify the morning, of three improve and these release going earlier, by issued are in or costs weeks call now GAN, the

get that have forms talked would weekend in X different as of interest a neuropathy to be And Association gene wanting that lot screened excitement approach. been -- GAN a there's So from and have for have the this last diagnosed about actually Type patients meeting axonal they screening construct. lot who presented Charcot-Marie-Tooth of Charcot-Marie-Tooth eligible of case therapy the therefore mutation and

is dose. identify to than going critical I earlier more think be So patients

dose we that argument equivalent dose. the generally approval. we in an the total X.XEXX from for an should with dose VG. that we the go may file should medium There's go the high high There's equivalent from if dose high In terms to low have going stabilization generally an we degrees the means levels medium disease or the what it that order of of argument

dose, saw Some And the say will -- the the low high concerns, the what file be -- high of safety actually, high anticipate it dose is some will to don't a dose the X.XEXX case it's medium to up safety profile. depend encouraging. would low dose, maybe is going of medium sorry, that's drop the going medium and on additional on I from high. profile the we down I very If the safety medium at very,

of not You're in huge drug, therapy jump dose. for doubling is gene amount which a a actually the

for with clearer heard plan And will become high think to as share I we bit dose the talk the data and a we discussions. regulators. clearer actual and we when on So will earlier, we'll you dose filed approval once those become

other agencies. one will be or have going would high discussions the is dose first on dose guess my and be the New then with But we'll my it's guess. that The in those be to Year, either medium the January high during filing

Operator

Thank you.

the Our next question. of question from Oppenheimer. your proceed DeGeeter line Kevin comes with with Please

Kevin DeGeeter

to with from guys, as ones gather Appreciate enzyme about on robust for regulatory on patients building on appreciate mind. from but are I maybe Hey taking guess on perspective I in see a to be two And you're my regulators. to do December follow-up quick thanks questions. expect of from should you this need clinical a we that of what updated for have to path, duration how about duration guess, follow-up, an in you of perspective, regulatory HEXA expression think a I How you'll think update where safety patient many mean Thanks. kind I discussion with just data perspective, the you'll thinking then GMX. to base? discussions able kind

RA Session II

for take morning, second question. good don't question, question. and the Kevin's Maybe you you your and Kevin, Hey first take if thanks I'll Suyash, could mind;

what that will as as is will patients identifying question, true his patients fantastic in we done this first say is be our and advocacy job well I globally. that Affairs is as that global a Med of disclosed Group well a What update. group, And as Suyash I'll the collectively patient haven't number our team the with study. have On say

we approval about literally world all that. And over fastest patients changed what could this around And to from patients our ultimately so getting we're were from what's the the quite world. potentially look like. identifying pathway is Essentially, over excited all the because really and mindset

And are that say It'll what track and to multiple have the what there, that. case we Suyash disease getting on I the and fantastic out patients I'll also say a I'll if find from will out And therapeutic led finding is and done team a our so from a perspective. teams rare this group patients the and gives say alternative And patient identified KOLs, confidence having tend again a to have really there's be have you. a job advocacy And up patients When screening on double-digit be have perspective people is really his maybe to travel ability treated. this making a know Suyash say they're make sure know the that on. worth the data. running that an territory sure us multiple patients. over discussion, and to typically more territory there to in is that if that they not epidemiology people a assessed study Again have of and lot that. I'll of there's this the that has now lot actually the

HEXA. Suyash, to I'll around so HEXA enzyme want of just duration Kevin's activity address And there. question and maybe stop you

Suyash Prasad

way step Yes. just This think is it I and take the to the about a what is good that Kevin and of back think really a question, happen. anticipate cadence might

the sub-units, cell, It brain pops bi-systemic down DNA the the travels the the to the they ganglioside. out, and combine starts caption the to drug breaking brain, sub-units, intrathecally. alpha HEX producing going we're give So into neuron, beta starts GMX

expression get probably to should to get weeks going then enzyme thereafter. you maximal four shortly you're HEXA production maximum and of Now transgene three after dosing,

one it time a going I CSF see to but time treatment to HEXA some for at for should My is the transgene the also one with see point -- of you're go over point going experience, which probably month six that probably reason kind really. is you're we take that And used months, at one that XX-month in six months, transduces disease will you've year. month, at month guess up three -- XX three-month elevated don't CSF time levels is expectation then style, activity to that at we point, or unless CSF producing is in months is still had, cells. or sample used take we I the guess in this perpetuity, less is stay insult, levels, maximum one-month take point, we at one levels that and it's the and time. have that elevation we at And relevant earlier our is So one and we the the that maximum inflammatory will trans will will it brain you by at trans level where first discussion patterns, a guess my once reach and of don't be the the In time regard immunological there more the type with see take a not time CSF. an will point, parallel which elevated case persistently in the levels -- the any but be levels. should persistently for reach plasma, the HEXA in is My diminution think brain think in

is enzyme high persistently. the levels will brain guess these So transduced levels the once enzyme that and the is stay my

chronic degree where over of our the models time. But enzyme mice time. this over can from do CSF of Now in we time, see We what levels raise at our we studies levels across in can't range them enzyme we is see take of mouse persistently we've look some mouse seen over to a programs. and plasma unfortunately

So enzyme my is see elevated guess of to persistently. we're going levels

what much we're by -- see if think to guess -- -- what probably the persistence, increase, how want that Now My they enzyme is regulators? at we'll I probably going required they're to see a durability is nice and a in in if at of six-month the but seeing enzyme levels once go point benefit reality, clinical usually might good data, regulators point, at filing the time that persistent consider year. six-month time we on

year, is good months how And term. But guess that's seeing will at the if case probably it'll on so clinical make once but my we push levels. play over a a reality, regulators in my in will enzyme will things guess longer six persisting back effect back and the we're

Operator

Thank you.

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

Yun Zhong

taking Thanks CLNX question. question morning. much This for good very program. is the Hi, the on follow-up a

the that generation you generation and confirm, had that it still into move pivotal be will How components optimal possible going from change pivotal you safety to to going given Thank the comfortable you're comfortable be seems FDA do wanted one to study? construct which to to two. any to feel discussion find of a you. will second-generation quite lot confirm to there quick you some and allow study, feel the assays doses into the that with with Just have

RA Session II

Hi, in the please Yun. Thanks if chime and question. start you'd I'll for like to. Maybe Suyash,

change multiple subtle with to concept of aspects changes that's while of would that this the a actually development. making that IND-enabling level the So made across portfolio. academia the change of basis into program times CLNX we ultimately what our done can we data programs before the We've our as data functionality generated essentially I aspects that into will these from proof and studies clinic, certain there And forward are collaborators, clinical done forward a changes construct, program. and have generated on support that's using consistent multiple from to moving and the because CLNX we before these say we and been maintain some been we've then that be look know that of taking it

do similar FDA and by there can or is -- order that's So necessarily another of the this data you not next we multiple we documents this, is how essentially do right. there's construct guidance what do to product. been reference is one there, on movements What generated from to notion think -- to massive know construct in

So Programs; ultimately into Therapy We've in of they're clear most with both into and uniQure's and I also proof-of-concept data around hemophiliacs. IND-enabling it the from precedent one Gene seen in world, this animal that's agencies recently the set setting. been clinical clinic was by moving studies believe multiple the

with discuss discussions across your our has on So been question this the this. precedent program. haven't multiple comparability. in the comment? And -- New Suyash I'll we've for the to And to around we stop yet the around discussions planned had Year, and Essentially, want portfolio. we FDA protocol for this the New second program there. Year there plan with approached maybe nine this you discussions a is to FDA

Suyash Prasad

And -- suffice of a it the talking Sure. degree to to modifications an And much the optimizing details be impact. mindful, is that to -- we're from But spent construct we're becomes reasonable we've changes I new we time safety perspective. it have But and say it so very that the package. going a perspective, And that a there's some but the into think minor where benefit where some the they're use to about I we from the won't change to efficacy benefit manufacturability that of a don't we perspective, benefit proposing. very, whole think want a from modification, relatively because will phrase considerable construct. changes think we go

the the change construct It's to in likely we're very earlier change -- to a changes and simple mouse we're minimal perspective to animal. make with to from bridging planning combined a duration need once But it's study, pharmacology/toxicology minimal we some likely with of line the work. model it's aware But short reference perhaps in to first-generation study. what going can't very are similarity again, work can construct. We what to allow bridging a our we ability first-generation reference us

Operator

you. Thank

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

Unidentified Analyst

Eun. is this for the how mostly AAVX Thank Thanks between progress package of curious your our what anti-capsids of for indications? is I questions. taking different on of is what just Nancy you. and anti-to on range during [ph] the is, on capsid this Hi, production was and on the current ratio the ratio

RA Session II

thank for that's for XX% we the our I'll one have full our of and consistently standard won't go portfolio, to question. our an that's say for kind consistent, is, of capsids, across our programs. is because each into extensive What Hi, you we and strategy portfolio. current What I'll such say strive

ratio, XX%. that GMX what full that. of can than full the I say, better actually -- do above program, that we've we for that our ratio gone And sometimes And

so consistency sacrifice of program maintain for material. some level current producers to yield of say others. And always is, support some So whole platform obviously, what to that's are our in every kind try notion will quality we is say our standard also, than of I'll and I is, But we effect. platform, ultimately what what manufacturing high this is different better will

be that one And can minimize so Suyash, more see real which is capsids that into safety a we that's something probably full of make of aspects high-quality concern concerns, the we're that sure comment? to patients, want ultimately, within and we've you to important manufacturability do the to which any us seen getting field. now, good,

Suyash Prasad

I'll question. here factor. of always some what is this does importance really comment. in field to believer firm do I've about and and in mean? really we for find is, hard without Yes, direction the moving presence sacrificing a think excellent have this possible. anti-capsid I anti-capsid been firm, I the so What weaving it's a much years, as as the think what to manufacturers yields the lot many of And is tremendously. of that this remove A Now

then feeds people at are therapy And some safety concerned of about we've reluctance patient, AAV which sometimes into so remove anti-capsid and unnecessary try gene that there's in to the borrow the my seen and the looking the load, issues perspective, anti-capsid. just add From space.

about about physician now in sacrifice with of quite And -- Significantly and as order patients. well to yield than as that anti-capsid right RA overseeing least get we that possible. appreciate to from sure have as little we purified that. I'm as is programs, alignment, I've these very pure some highly intent We I Now that's safety been the the we the really which our full will fact product of make better XX% pristine for as pleased always at length do talking this our full. and at better our

work to we characterization less and than products high XX% to really Officer and think patients I our important greater quality yes our So inject got Chief than sure Technical and for our a We question. very it's have But intent try Fred, see with good on. XX% early screens make that products. closely with we've is

Operator

Thank you.

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

Kristen Kluska

for everybody. morning, Hi, good taking questions. the Thanks

anticipate you to thinking wanted Just at look trial of terms have prevalences? of year, about different cadence trials ask these enrollment, the how you're given all as in indications, running next the clinical different you

RA Session II

Hey it for I'll over the Kristen, to you good Suyash thank answer question. morning, question. to and turn that

Suyash Prasad

few question. I Great to Kristen. a themes It's you, program from program. different a common There's Thank say. would Yes. little

First but of anti-delivery platform approach HEKXXX, a our in the talked platform actually approach all, we lot AAVX many about works other ways.

in similar that vast after one, of clinicians experts. of One or is pediatric, neurology metabolic physicians. are in the GMX frankly sale deal we majority which looked Southern is with sale Rett generally

a And finding we of similar. so lot points are of touch the investigators in terms

recruitment. that's helps So that in I one us think terms thing of

thing other the is the more ultra-rare there helps think -- that where I diseases are us where the population. for

or we're U.S. the sites. then plan to example. the diseases and patients or two X,XXX and around from to one have sites patients We those sites prevalent have ex-U.S. for transport So two the would in thinking one world

on list So to or different patients rare. for less that, a Canada, of patients transport GMX enrolled have the the the And and and been come that from one that We very well to we're world. In study screened focusing GMX ability the we currently. worked a for all from get for program. U.S. other have countries diseases are site patients heavily that's little our program over It's for only the Canada or to to Europe.

and excellence thinking XX,XXX congregate clinicians books. tend like and the on XX, to where XX generally there's is enrollment their patients you're have disease will are of recruits because It's a more patient patients the and different. in where centers little patients U.S. Rett So Rett easier, a Europe little they syndrome XX, with --

investigator syndrome. key we're one Rett considering have XXX last leader, opinion one the patients We with

a And as clinical so we can individual use trial. that

educate that don't there populations. three problems we're And these studies principle, led to McGinnis heads Taysha, and going really who There larger help to three and two a wholehearted I Affairs. sincere we heads be anticipate in so but work sites, to advocacy Medical patients fields. with real ask patients Advocacy being by four leaders, to patients take study families, would But finding taking single experts find who potentially in way colleagues on with that opinion roll some have Emily patient's they're patient directed Patient who whole or the groups just we site the are it enrolling in at we the the therapy -- way and to means part. to what you probably We in approaches trial gene a this of Kome would with want So cost. and detail Okposo for in do I And don't engage side. a very interested and key

attend of teams approach the We and is clinicians doors of support. activity to that's who them with, find the advisory on And then finding want third knocking ground, boards. on medical our another them, route to on talk the have patient We patients. science layers with

three approaches really are philosophical find we those used patients. So to the

seems found on record patients far it and have for many track our we've detail more many data say, trial, that's that for to we been the in I and GMX, when with GMX. not successful we've clinical have approach As all but thus that we'll screened many, share our update eligible, been you very

approach the our same the programs. of anticipate across rest we so And

Operator

Thank you.

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

Raju Prasad

Thanks for the question. taking

many clinical second on GDX deal marker. initial finding And kind with do benefit seems have program, how initial Thanks. there here thoughts curious changed is of biomarker, there's being but genetic see then, GMX you patients you increase to could just on there? that Just is the activity? a do X% it by of enzyme know And clinical measures any the a kind any show anticipate of like for that in to moving benchmark we that's kind the this

RA Session II

Raj. happy both Suyash, and the for to Hi, some I'll morning. Thanks questions, the Maybe for question, question. provide second then as well. take Good color

Neuropathy those was first our in important Charcot-Marie-Tooth on only partner include this for collaboration And more was Type collaboration with NIH commonly was genetic both well as phenotype both II. that of and patients the been history neuropathy standard And not groups the number clinically and Foundation. essentially and Foundation at advocacy this GDX, here Charcot-Marie-Tooth that So the the Hereditary this as neuropathy have diagnosed It that Carsten panel, in Bönnemann partners particularly excellence, to also over with again, And now screening. their U.S. giant last a for patient as of ginixonaneuropathy collaboration data includes undergone it's the are eight the but both it the athermal leading around extremely years. Charcot-Marie-Tooth Charcot-Marie-Tooth question natural particularly Charcot-Marie-Tooth because and Association, onset identified Europe. fund centers of with a was the have that misdiagnosed not based on our late a robust

one sense their to later also but form disease early the their sorry early diagnosed teens in in Typically the or it's kind is of kind or fifth in debilitating, into disease muscle form of form -- the life it normal at to life. least succumb the -- of of where tend these and their the life impediment sometime teens, either life, or of that diagnosed life understand quality onset the their severe patients but significant that around of bare the disease. this are kind to early they of the of at decade issues age they of live onset We not a strength. And XXs, issues essentially significant onset is the three later limiting extremely span around quality birthday these I'm of walking, disease, patients essentially late in have it's are after have and fifth

understand large with II kind of of a because the diagnosis. a and Charcot-Marie-Tooth genetic undergone we when that hasn't there off a what population cause is were of in because it's a necessarily is umbrella this So based prevalent just that pool essentially no there's number is onset not test, mutations that the is genetic there's that there for, diagnosed Type genetic called later screening of epidemiology, person patients particularly form, that

the most think actually of patients genetic are talked not foundation, CMTA are there's to Neuropathy X%, a we well if we as as So large Foundation both to that that a of both group having be and Hereditary is more likely the agreed portion typically section of know mutations. large misdiagnosed a which large these there a up patients and underpinning ginixonaneuropathy going they to

patients U.S. there's Europe in both we out number and there. large So think the of a

work of now to doing any of ahead type these commercial so launch. we're eventual identify regulatory the right of And kind and approval

large not answering we question. what a number and will but will your say probably number. specific give won't So question, I'm we you say, I put your But it's of I answering a patients, are we number Raj that me you second to, there those. are out hope out there question. of a X,XXX patients large above identify reminded mind able that to number of that do your just

Raju Prasad

measure it timeline GMX, know the clinical of that just over for seems early obviously, benefit? natural maybe curious for as into history of thresholds X% biomarker Yes, though translate to a with the kind may when

RA Session II

question. taking you Suyash, that? mind Great Absolutely. do

Suyash Prasad

that just weekend, on meet to panel I patients and GAN Association one to Charcot-Marie-Tooth got discussion, Yes, make sat on And that a the testing. the only with that, was and many analysis clear, have having and actually there the were Charcot-Marie-Tooth many point Charcot-Marie-Tooth it's mutation Sure. and last adults that comment the clinical genetic many families. spoke or diagnosis are I because always who individuals disease the there a meeting it diagnosed

will So found, advantage created. that. be our shouldn't a partnership And expectation take of is of large of think, a really I GDX there's that who that this but will number we've significant patients patients, pool

a seems that how to based I to had good improve on I modify weekend, the levels cadence With discussions enzyme GMX, that the it's over and very I time. last I expect question, real meaningful. of think Just regards to and subjective talked

the going to And reason it what that may with see this I improvements. very once don't neuron. in GMX improvements, you to [indiscernible] the physiologically Initially, the damage and it's the accumulation take of progression more then clinical cause lost get improvements. longer happens think And think but is stabilization of is progressive, destructive say that rapidly the and ganglioside a clinical you've disease it than of get I neuron, disease. and be of back. I for the actually a a is after acidic you fibrosis, contents, results inflammatory lysosomes less the to rupture in swell GMX enzymatic And cells process, neurons. death it And

important the going be additional able So I see life, and you're this you've of inflammation a And screening going of the to to lost treatment neurons. has And resolution may newborn some and of to neurons, improvements. produce to that's had is some then think, if we in damage. and disease lot there. to chance But have the not to when hold. it'd stop neurons, patient if the at has significantly on future start That HEXA this child the treat loss take some affected, had be neuron the deteriorate lost for earlier in If best point you're going the in to be you before clinical see improvement too chance they've a a the you will why is get enzyme much. before

host looking at Specifically in perhaps improvements. general expect at or developments. earliest quality the whole to seizures and see, of six you these three should We're in terms scale clinical lack maybe we're Behaviors, looking at at general hypotonia, the time, and or -- by We're a scale. but My scales. We're I scale, collecting, control, within of months some is dysphasia, the ORCA bay scales Vineland communication a life looking the Adaptive of indicator the just assessment clinical global guess at looking the hypertonia looking at stabilization see We're Communication months' X what the impression global impression. some will looking of Observer-Reported EGs. We're what head by performing we're measures. that be Ability Probably measures. of

See after And reacquisition be of CGI then also to I'm scale I've in potentially and in have will to greater improvements and patients think six show hope some older that probably three the some We the by would dosing, which you'll you see see after So in you're some improvements, milestones, X. see hypertonia, going guessing in activity. some improvement diminution bay the months I will measured younger a But some improvement hope likely at loss, wait there. will the seizure to to than be. dosing, see least some patients. months

Operator

you. Thank

JMP from next Our question Tuerkcan Securities. question. of with line Please proceed Silvan comes with your the

Silvan Tuerkcan

cash picture Yes, five, good these you as thanks potential be so just all morning, end potentially big six deeper ability year. about and programs thoughts you planning and expands maintain your and all especially the you. prioritization will my maybe your that for into Maybe some with of trials of some regulatory rapidly, great. next in at and will attritional, question. the expect a pipeline to taking that manage discussions view or the to manpower What about detail year give there can be your partnerships, us Thank of

RA Session II

Thanks, Silvan.

the So thanks for question.

when also scaling but company about integrated the you blueprint So not company kind and and were supports what to hope to is what put therapy we company we as of be the discovery, fully gene together start to this what is is company a frankly, eventually think commercialization, would going quite say, probably only hoping I the to we early of executing. build-out the company the exactly that

support those from disease. Scientific intrathecal think concurrent are Dr. the I has front, the sense, in Chief on in monogenic a year, completed of good but Steven shown CNS BD our a central just GMP interaction HEKXXX this all been ability suspension, activity five the they AAVX, programs the Adviser, proof this Gray, albeit coming pudding So run, manufacturing, non-regulatory around the thesis of kind delivery, lot year,

that kind quickly creating the to that allows see us certain to of So next. one a platform there's of you from can we're pivot program kind essentially that

year our last public programs. program; with As we this stage you last quickly founded September public on year think recently had year of as those. and we We year, company progressed IND-enabling a to early about scaling, data the in in company one and last anniversary finish that finished we'll reiterating was company. hit just a the And studies. plan stage programs year, We have we're to three clinical with guidance multiple to have clinical we one year track readouts five our

last what with the is plans. beautifully, on allowed to with And that be really year has finish And employees. XX performed to say really the we'll execute team so would to year, ambitious some I finished this able employees, us scale finished so to with ability -- year XXX we XXXX has close we

we clinical of and into a but ongoing for a supportive of out will Syndrome, continued year, that activity year data we've get XXXX, this building year of would kind kind updates end of cadence of CLNX of value-creation kind foundational from clinical as couple laid be data of current our readouts I Rett As data, think This of year, also it programs. next Taysha. a the enzyme safety the efficacy at

kind happened where a as point So the of to XXXX right. really constant there'll XXXX, data, foundation, get we to laid lot into drumbeat us to of the move be work this of

programs in into and So plus updates programs newer next in ginixonaneuropathy and the that the we'll GMX be updates on moving CLNX, our Gangliosidosis, provide in current will on CLNX year. clinic ongoing

scale, the we've year. ability So, for And shown we've ability us, to do that. the continue to shown this we'll execute to

provides the a our perspective. what into I points regulatory ginixonaneuropathy half cash inflection second in capital. definitive front, reported without multiple from XXXX, This we've value the consist plus cash guidance the also keep having clinical our of some data program, On raise gets think high to us us of to readouts past quality need additional

foundation work work just across really work I NIH business, of because as to at They're to also, but the partners proud with, the from think we continue have company for have. kind have growth low will and this I into our like of over is of forward of kind year start foundational you executing moving you with as the been so XXXX. to well achieve our at the here collaborators employees what phenomenal on support have to what for phenomenal I'm as this see XXXX got to Taysha think have I partners But ginixonaneuropathy So to kind the and see a Southwestern. aspects of year building us we undertook we extremely the hope laid UT that see moving collaborators all

Operator

no are There remarks. I over back you. call Session Mr. closing questions. will additional Thank or further turn for to now the

RA Session II

building on So wonderful on Thank this day. to year morning. see part we joining we you from portfolio, portfolio and the of so to and the Again have for and have continue had you look first we this guys call really guys the much appreciate a XXXX. of in everybody momentum remainder into posted that forward year for the you progress the the the this

Operator

presentation. Ladies and today's Thank once participation. you your gentlemen, concludes for this again

disconnect. now may You

Taysha Gene Therapies (TSHA) 10 Nov 212021 Q3 Earnings call transcript