Orchard Therapeutics (ORTX)

Renee Leck Director of Investor Relations
Mark Rothera President and Chief Executive Officer
Bobby Gaspar Chief Scientific Officer
Frank Thomas Chief Financial Officer
Anupam Rama JP Morgan
Whitney Ijem Guggenheim
Gena Wang Barclays
Graig Suvannavejh Goldman Sachs
Yaron Werber Cowen
David Nierengarten Wedbush Securities
Esther Rajavelu Oppenheimer
Call transcript
Due to licensing restrictions, you must log in to view earnings call transcripts.
Renee Leck

Thanks operator. Good morning everyone and welcome to Orchard's Fourth Quarter 2019 Investor Update.

You can access slides for today's call by going to the Investors section of our website orchard-tx.com.

Before we get started I would like to remind everyone that statements we make on this call will include forward-looking statements. Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risk factors and uncertainties including those set forth in the most recent Form 20-F filed with the SEC and any other filings that we make.

as statements of this be today as our forward-looking views represent relied any date. representing as subsequent only and views addition made call on our upon In any of should not We specifically or forward-looking statements. to revise any any disclaim obligation update

Rothera. that Mark with and the I'll over turn to And President our call CEO

Mark Rothera

Good morning. us joining Rare happy Thank and you for Disease Week.

have transformative view really themes this should a reframe and modified the underlying severe rare means even harnessing therapies our to to well seek stem curative patient we year's what fits power This our is One cause At of a campaign the of we one-time be the blood disease. investigational of can are temporary that the effect correct Orchard the gene diseases. cells term label that with genetically rare of potentially as it considered given provide. to

across outcomes or diseases have XXX different and now years XX seven to durable patients demonstrated more. out over treated We going

If of down into and supporting years clinical really level patient of about that patient you is to break that's our terms response say on years data profile clinical is all the in our this therapies. of durability XXX This of of data exposure gene safety. another cumulative

time. components. and is from a number business Our platform highly regulatory key strategy increasing down can into gene for to multiple global manufacturing be steps our valuable efficient strategy therapy over benefiting by programs efficiencies commercial commercializing The to of executing create broken value via rare on and diseases

corporate strong. capabilities approximately strategy organization industry-leading company commercial that people medical is built manufacturing in across we a and have Firstly integrated research an with fully regulatory XXX affairs in

clinical pipeline gene established of stem stage we've cell Secondly extensive hematopoietic an programs. therapy seven

leveraging CMO the in finally phased to establishing use Fourthly our potential footprint we're business an but development chain are global our additional emerging tool and keeping capabilities. as mind a we a value. basis. efficient global relationships And we're in-house also a existing establishing commercial supply Thirdly manufacturing on to create

in are three and toward our these of to approvals There programs ADA-SCID MLD exciting lead WAS. filings turning regulatory number launch. Now and potential programs near-term milestones progress as a

of our MLD United months. Regulatory BLA launch in We for for for year the behind. MAA for for for U.S. BLA are the filings the United OTL-XXX OTL-XXX second a OTL-XXX XXXX. in Europe obtain plan in OTL-XXX to of are the and the half is approval half OTL-XXX XXXX. not of far for with key or filing filing the that completion for to XXXX planned rolling anticipated in WAS States regulatory file and for planned within States Europe For the XXXX. early priority A first ADA-SCID and in late OTL-XXX initiate filings XX is and in BLA

efficacy supporting ADA-SCID work is for clinical and safety and The WAS complete.

For work and ADA-SCID the ongoing patient as release cells. with on process validation runs commercial drug per FDA process guidance is manufacturing using criteria

geographies commercial at For preliminary It's the infrastructure lead drugs. three plan that the only to serve as that with our All of and we for cover sometime patients in for that the data $X.X reimburse WAS accommodate enrolled future we ongoing WAS focused study we've establishing additions intend opportunity needed this least annual planned additional launches there year. will believe to we orphan incidence-based launches. modest together and cryopreserve billion is report the programs ADA-SCID the a expect six MLD our the for are in backbone to

are treated importance supply market patient identification as global readiness with area focus patients of is We're let's commercialization this to better infrastructure identification phased access. commercial on four the imperatives an key the clinical patient strategic outcomes. their on build MLD Now and that high focused preparations: the strategy. are launch the long-term a earlier Starting

So the a disease of XX% far each of to launch. that be label the forms and XXX OTL-XXX therapies. XX disease In the at and typically year so targeting we studied we'll XXX patients MLD that population we've eligible pediatric reimburse approximately patients infantile MLD juvenile with we estimate at rare these approximately in Of the be countries will launch. are born for incident estimate

if our have with identify into prevalence our progressing slower to disease label. eligible adult account and patients launch expand is to MLD patients we could successfully MLD that term XX% ongoing. we be target take the Disease could of approximately up we terms area. longer of the to awareness In we This near these believe label. figure can form assuming a of we order XX% juvenile first patients In secure MLD and at initiatives grow assuming pediatric living key

and specialists MLD Now other patient first-ever improve using to Together early a symptoms an treatment suspect is approaching that sooner. is MLD a for diagnosis. of physicians regulatory approval resources patient pediatricians educate a tools on to there MLD for test strong diagnosis incentive and so advocacy groups are potential we the targeted and with

appropriate tests important Improving the another to is diagnostic access area.

program prior to We screening have help online. identify a newborn coming sponsor patients to diagnostic testing

Our confirmatory goal of is that a early within days test can done. XX be suspicion

geographies that world a a second patients blood doing We're commercial validate States initiating footprint Building the the these Italy and imperative. using as Our around global in to York both a phased State it's dedicated now this have When United enables New ultimate with is possible. universal bring the and collaborators and starting disease product these a through on a goal An is as our combination studies developed medicines we soon approach East you with newborn to for team to coverage to assay higher team spots. Orchard where patients we're a the for direct adoption Turkey commercial and launching via find national partners been pilot of and focused Europe important rare screening of programs. assays has support screening some ultimately highly a example of also. presence in in Middle patients but and expect also incidence experienced

Phase which one mostly regional and the is complete commercial team EMEA is of a includes FTEs. buildout XX

six region next that countries Phase qualifying end or start expertise treatment XXXX. filing the buildout and in disease centers in potential with at under approximately America next reimburse approval. early this on are We XX in at OTL-XXX the other of of Orchard and subsequent drugs coverage knowledge. Latin which will year particularly will countries parts transplant U.S. to in This and grow key world extend over orphan will neurometabolic a in our in typically months three EMEA Asia. and the is the is area launch of way specialized two Phase working anticipation the the

imperative supply. covers third commercial Our the launch

years We and have supporting Milan MLD also experience have been commercial manufacturing Italy. in working have partner great a MolMed the for in eight on program Strimvelis. based now They

qualified the a neurometabolic goal gene demand between the using including at there is with have is broad therapy inventory tremendous treat call. disorders. and of hematopoietic launch high touch supply fourth MolMed access centers. Our to cell unmet pricing believe on vector a and other and to approach a and market robust potential with neurodegenerative around need strategic the stem line chain I'll at anticipated range treatment the We in close of imperative diseases

Bobby? develop Bobby MPS-IIIA topic it hand along updates over the MPS-I providing with this from to to now me programs. Let and

Bobby Gaspar

presentations. and our start I'll MPS-I which also Data in an by MPS-IIIA both those be WORLD featured overview initiated. study in was were at Mark. I'll highlighting MPS-IIIA and recently proof-of-concept briefly Thanks providing of

to MLD is Our enzyme delivered approach for the across barrier migrate both that such HSC results that promising ex ability diseases to deliver approach the that vivo in enzyme same HSCs of has CNS. the use in blood-brain gene and the the therapy have overexpression

cohort MPS-I. that median six a whole the months follow-up to want I patients. seven some Let's start time is out with now discussing in And evaluable spend as proof-of-concept to

and in childhood. the As skeletal cardiopulmonary neurodevelopmental is however storage lysosomal leading death the of a treatment. significant transplant of severe cell reminder remain after Allogeneic MPS-I remains disease manifestations deterioration characterized disease by complications stem care; early hematopoietic to residual standard a manifestations

showed by and months heparan have urine in supranormal three post-treatments. within all later patients HSC dermatan concurrent sustained the CSF or As in the sulfate stage normalize therapy CSF. accompanied a activity both fluid IDUA and that bloodstream to the of all the was gene rapidly and evaluable cut six cerebrospinal engrafted in patients drop This undergoing and

patients The aspect important most allogeneic HSCT strongly enzyme murine of expression. that studies undergoing this suggest with clinical of outcomes correlate analysis and data of is that IDUA level the

with CNS and to of highly do level of the periphery published able long-term the HSCT For example therapy of a patients type HSC whereas a in study did overexpression large through in in fully lentiviral skeletal a expression MPS-I predictor significant achieved model outcomes. the IDUA vector-mediated clinical allo cells correct defects was Similarly was of a of not IDUA gene murine transplant wild so.

with year of are remodeling patient showing months score to of expect longest data the resumed additional XX XXXX. full results At presented skills in trial stable a improved patients motor the has before interim The cognitive and metabolic follow-up post-gene currently evidence is line growth with eight treated correction. and bone available we therapy and signs proof-of-concept be this in

of and well. is the and on frequent compassionate patient the first well levels This forms University enzyme to therapy treated very nine turn above upper were we data on has now of with our stable a most ex mucopolysaccharidosis vivo Engraftment of of to At limits gene-corrected who HSC normal of the MPS-IIIA appears approved is encouraged WORLD post-treatment. gene Manchester months Let's use at attention MPS-IIIA. present no cells one basis see treatments. the doing

trial. use order outcome patients and study. a this the months stage normal as in young is recently who review objectives. in of between MLD vector early the function in Patients the at treated compassionate the same asymptomatic briefly The because the and very have because damage ages of best we've a to We're three eligible two patient target for of measures of years patients initiated as and extent study transduction enrolling response treat the are cell patients used study's presumably initial or to seen with provide those population I'll irreversible sense are cognitive used protocols limited. those and proof-of-concept scope disease the are in CNS our

include As Key a and in living begin typically XX as in behavioral in primary we to months these addition measures of functions evaluate OTL-XXX secondary endpoints measured as daily expression biological to to post-treatment. therapy which first-in-human efficacy well at quality at of and safety in is see and life post-gene leukocytes the tolerability three individuals. decline cognitive years untreated and study by SGSH when the engraftment is activities objective

this preliminary we this year. first The enrolled and been expect later trial patient data to report in has

will progresses cuts are presented. patients interim As be enrolled the data and study

to genes the to want natural we and the therapeutic neurodegenerative ahead some potential look ability treat tremendous other areas. Using I of tissues CNS a to therapeutic is initiatives. to new new to HSCs there and now exciting believe more diseases deliver

and also will We do in discovery our external in laboratories by January we with and research through this announce were in agreement established to preclinical efforts London. excited new collaborations In a support leading help non-rare into need and our neurodegenerative including areas Dr. diseases. to in Alessandra for patients programs the therapy Biffi expansion for expert rare of critical a gene of portfolio new in-house additional

first our that programs her expert and established the partnership experience be MPS-I will MLD and invaluable. As

call data an Frank. and we turn keeping as on forward the I'll the to It's On time to these that matures. at Orchard exciting you look programs updated over

Frank Thomas

second on Then I'm I'll results results which our launches with in XXXX. million compared of end investments the and summarized quarter of by Starting rest outlook the our anticipated Consistent fund and quarter fourth fourth capital for cash touch investments we Bobby. our upcoming $XXX with start in our the going to $XXX the of we operating year at release. the into lead expect cash expenditures programs. bit the and ended morning's that reviewing this our to and are million a previous financial XXXX. our press existing guidance Thanks will the with for half

to During the fourth quarter Strimvelis. revenue related in $X.X million we recognized

XXXX. driven primarily to clinical were fourth of quarter expenses $XX approximately later development the compared higher stages development $XX advance of the XXXX XXXX. to in The in increase and million MPS-I by of through in was stage program cost addition quarter the prepare investments programs our XXXX. programs million G&A including Research commercialization our to of as The costs for SG&A $XX.X to for late-stage well public expenses compared the company million in was due fourth were to in $XX increase XXXX of potential support to primarily our as XXXX. operations million

of $XX cash We used in about to the of fund fourth operations million XXXX. quarter

expenses well call for quarterly facility of as launch to sequential as for our the wanted to touch in support the of on XXXX. due expect also burn increase to We in programs. quarterly in I growth rate use to lead the XXXX today's outlook OTL-XXX operating second capital to the manufacturing investment our half the potential

there be launch treat will how awareness and we portfolio curves We these it A disease its unique these each platform factors that a patient third a first? place each level a is And are will aid patients launch in have we Notably identify enter disease of currently identification? of and easy building launch. with first that will uptake commercial manufacturing include product high infrastructure has global can in few subsequent factors does and own rare of pool leverage to patients? the tools of to Second the our influence we a and diagnostic prevalent where as phase. the set

XX ADA-SCID newborn Europe. is in U.S. the already all and To an some like in example screening illustrate this established countries disease a in states for with

us that should gene to driving for gives identify we be incident able the population confidence this faster So eligible uptake. therapy quickly

likely for early the uptake. WAS disease patients example key have This typically been and live longer many of in will treatment diagnosed. make already like Another nature prevalent to of slower disease progressing driver the patients a a the due

are U.S. planning in to also therapies this these launch two quicker. happen adoption often can We first where

by assuming investigational is that be Turning our physicians Also there MLD This rapid awareness will be continent. to for raise in condition means place. characterized work phased an will to a screening payers treatment which Europe approval negotiations country-by-country in that diagnostic is launch first implement crucial initiatives with and rollout newborn before the planning and MLD adoption OTL-XXX a will mean are across in is the driving for to progression. we

second revenue approval we European U.S. generating to anticipate expect XXXX. potential lead in programs the all half We With revenues meaningful three MLD starting be by XXXX.

steps our platform long-term that to we programs approach. conclusion these demonstrating taking in position believe necessary we're and So the success for scalability of the

us my remarks we made I XXXX in company integrated in take and earlier As long toward industry-leading commercial and way vision a buildout building fully manufacturing in said continued the the with our of will investments capabilities. of achieving a XXXX

back now And to you. Mark

Mark Rothera

to to we closer our In Thank launch the address strategic namely as Frank. imperatives you four OTL-XXX closing get OTL-XXX market like access. anticipated for I'd

potential world. the potential deliver A seeking to one-off lifelong to a medicine benefit new are administration We with bring the transformative type of including the cure. to to

have approach discussing to we key principles our company which pricing been sharing and a guide to As that four value we've committed and will proactively with stakeholders.

committed to value. Firstly we share are

valuable responsibilities but think are whom our a very to the child. care recent the of to giving I an investigational to therapies average spends an for patient XX also MLD day intrinsically research hours gene family on medicines according

for of need. potential healthcare system these innovation the want to expect also future value disease And other certainly rare of medicines. from and are more the reinvest society we to some We in broadly who value benefit patients in this

the in confident own engage the gene therapies of term. follow-up so recognize sharing. the upwards We of Secondly long patients about in exist over our are seeing are payment we're XX years than in willing and system treated of that models the are still questions that risk portfolio XXX to more durability to durability response spanning risk share response if and and that required. committed Having is new to now we

we applying pricing turn informed committed to we and well-developed available value recognized to Thirdly, to determine tools have are robust best pricing. the in evidence and measure

with the experience conducted in their two well-accepted miss XX% three KOLs and of findings groups of MLD days this our last hospital Early child Unsurprisingly to caring that at time per of weeks with the these being exercise indicate to knowing For are close outpatient of in from were from XX findings like ago with leading On instruments this be away instance inpatient and and visit. unpaid forced project palliative. and spent and care the advocacy for That's suggest in visits we only amount caregiver roughly XX% family WORLD that children inpatient presented using from then average work MLD recently an for community visits year. an incredible parents standard is their partnership parents research rest consultation leave. their child PedsQL. six for away work

engage continuum about will our thinks therapy we system healthcare across help to delivers evolve stakeholders with pays Finally way the gene for the and medicines.

curative For managing successful to a years chronic It's forward symptoms it's interest potentially there that for in been about made conditions one-off treating everyone's to available is mostly and be of disease. medicines path patients.

for time you line attention. the for your Operator open you Thank may now questions. and


Instructions]. [Operator

from the first line Rama from Anupam Morgan. of Our or comes comment JP question

Your line open. is

Anupam Rama

the half gating given to so related? the here supposed you CMC over initial layering guess are it infrastructure how indications And thinking the it XX scope and preclinical we data really factors BLA's rolling the about second And be first then known maybe you what thanks next as OTL-XXX touch the are that guys, on guidance everything guess but so why in And completing U.S. far? on and wouldn't particularly clinical buildout EU can starting in think question. sales much. quicker market taking data? the to The several about years? one the Hey, would but Thanks well. I that size OTL-XXX the so the much on we for for OTL-XXX. the filing complete be it given know a quick within is I of the months as Is

Mark Rothera

the in one and launches. of was team then for additional about scope And the Europe the first and the the overlay size

large with It have. doesn't We've the team. the markets dedicated in is But are have the so as focus advantages major they France need also markets having for but FTEs have the highly out team in to programs to UK those rare our mentioned in Germany and we one hubs regional for we that guided disease think Italy. XX as Europe really of we and fact of countries a be focused biggest countries. focused team such a clusters of And I on as you of sort

we So treatment. from countries referential not centers with referred only adjoining those the into teams countries from that but to patients for qualified expect those we're building within be

capabilities some do group You at incrementally. manager good you that a the is bit sales of are established we general medical the how of about key Germany thing and scale asked with example of just for up. once marketing you've a really a for sort Well adding sort core like looking

You don't those another need might you another additional need treatment head another need is what people patients getting but general to don't to meet medic to need some manager on the ground you customers support you additional centers. of don't marketing

it is kind incremental. of So

the you're you not again MLD And the begin over centers timeline it's very is think well talking copy/paste. treat in and can MLD or And that incrementally start the with next the true the with this but same where U.S. same again about ADA-SCID a you we'll same we already is is I patients And patients. mind. efficient might few most other treatment or that thing the add patients qualified part WAS the are in year time centers the preparing what buildout to into a for

So, second the asked question was ADA-SCID the program. you about

something using which focus as we fresh. And manufacturing about for. they've that where and data is done safety. process a that the vector We've commercial commercial on showed drug guidance performing you're year clinical really the quite like our FDA essentially we're per work the work asked is last cryo talked with is process using material that So efficacy that specifically patient key the cryo right we've validation

ongoing giving. this is I present to XX the that. then guidance to That do in for filing. close is of guiding I we're final feature initiating in alluded we'll the think will BLA rolling work mentioned we And you we're the year. as to that have up to And just the that moment half first the that and So the we to module months


you. Thank

or line next Whitney Ijem from Our Guggenheim. comes comment question from of the

open. is line Your

Whitney Ijem

ongoing access. is follow on Kind should reimbursement work from doing a one logistical or of to side. coding sounds guess kind on work around of the we considerations up sort like lot the a value some market that logistical I be thinking what establishing of side perspective any type on you're like is about? the This of comments around But of other reimbursement

Mark Rothera

focus of launch first from potential access point is the the market view think Europe of in I of half the OTL-XXX second year. a in this

there the of with are to and benefit ongoing. payers many have making and that the that convey the that the appreciate and background able payers So that the product we're been sure to durability data response. that for aspects to patients the Engagement

pay the of you've lot educational the very One signal compelling. dataset a which treatments this given very is a we're a product this that is exercise. thing children severe for for willingness need unmet a that condition So with is an high and seen fact no and that very is clear delighted of very affects today where to are there

the was As order alluded Germany as the I approval think of And we relatively approval this to a countries have complete lead so there you remind forward country frame in are variety on of to comment after it's Frank's negotiations. the a are launch sort processes also one-year know be to prepared be is possible. different move and about in engaging fast typically in different to in you able where Europe as in those to time well and can launch in to phased quickly Europe an you

If anything So that let your know. please to me know answers I need there's hope you question. else

Whitney Ijem

Maybe just follow-up. one quick

sort point? with you about reimbursement can of kind same this vein give reimbursement uptake in think as thinking in color the guys kind geographies at those the any about the of European of or in frameworks penetration difference U.S. of markets we versus that Sort into markets how the or and that again you

Mark Rothera

So it is a of cascade Europe. launches in

in launches it of I as having specific for different a collectively XXX is each MLD that market of get there's think to would favor process I have we you inhabitants and very severe. XX for really a know terms one of very it's that the that impetus of approval. say launching with countries. these large a product So the And it children market with country is a cascade million treatment in the quickly things like no this is to

the compelling. is data And and so

there think willingness for to really a I with so also And now time is work us these because children. rapidly these but that matters through prospectively processes


Thank you.

Our move Instructions] or line from Oppenheimer. Esther on. Rajavelu we'll next question comment the Okay comes of from [Operator

Our comes next question from Gena comment or Wang from Barclays.

Your line is open.

Gena Wang

Thank is you I two. the for MLD questions. the regarding launch taking my have is One other and regarding the pipeline.

Mark launch MolMed that So have the launch expected MLD to produced sufficient had for inventory just mentioned wondering demand. you a will meet being

and patients? wondering number capacity of you they vectors And MolMed how those the the is demand can expected time? the And to in the also inventory many terms Just what plasmid? patient launch product are referring the at the of of same process

Mark Rothera

experience on eight the obviously already for they that and been for working have Strimvelis have MolMed commercial now partner we're program. manufacturing program to MLD like delighted who years a doing have Yes the

it's great have this So partner to a program. on

a range their the different is programs. demand. programs have fungible So of various importance flexible you we actually we And with on of depending work stages on capacity MolMed if like and that in whole

manage the meet the to place the numbers us you that this things make are If which flexibility that there to suites allow make matching let helpful. portfolio certain know. the to not the wanted available the to was is supply to our demand. ability titrate we we demand. across with that very And is But programs at But had can guiding have we sure MolMed. to patient time to we'll also So we're according thing is demand one our anticipated we alluding I of specifically. them. manufacturing was there of to Drug product in in vector sure At intention changes rapidly with inventory as because key future again being with MolMed we're

Gena Wang

question then regarding the And pipeline. my next is

on will the in endpoints what FDA to future? the the you with the MPS-IIIA and wondering the past based endpoints approvable in your MPS-I for other with those data the what discussion approval start just latest drug For thoughts could of share and and us the be

Mark Rothera

Bobby. that turn over to going to I'm

Bobby Gaspar

So as first far as MPS-I let of me with all. start

as the the parameters; is are levels. moment The study. this endpoints in proof-of-concept the in are this activity at enzyme efficacy are reduction are study endpoints So a proof-of-concept clinical far endpoints primary as concerned around where exploratory currently biological substrate

will data we move from to registrational proof-of-concept a study. study the registrational from and endpoints for will so this And study the the the inform

skeletal say can't so having are thoughts in And about defects and we you registrational obviously around the we'll meaningful And clinically endpoints would those be endpoints. but the about at to obviously they the be major are in study need what I'd moment cognitive etc. we give defects details issues that MPS-I

we'll you. got And how so agreement we'll look detail with data we've once And those at that that we around and can share capture to more in the registrational study.

a and we're MPS-IIIA again cognitive are are And University the that at again far Manchester. behavioral at that As within the proof-of-concept endpoints as that there is concerned moment are in endpoints measured. being study of

study having enrolled. the just so that started And with been first patient has

Gena Wang

regarding question follow-up MPS-I. just Bobby

has this think diverge and that based or will could approval ago. So change be IDUA then the still endpoint think also you Do you on X-minutes the a test. while from the SVC that the that got case this? going been forward walk

Bobby Gaspar

we a abnormalities proof-of-concept includes at we're the I'd at skeletal exploratory think I we're say mean IQ within that and etc. number at looking at looking moment growth looking study the are endpoints of I

of at looking things. So number a we're

since X-minute you've is problems abnormalities severe ERT that correct doesn't of test I walk the about before have have basis the the know we'll to etcetera. what I'd And talked which ERT with take time. the for associated But things board MPS-I. say we registrational being of And study. of one first remember ability so need decide And on endpoints approved on CNS the will on the that also the moved to major one be

So capture study. within want to for the our registrational would endpoints we that


Thank you.

Goldman from Our Graig comment comes Suvannavejh line of the from or next Sachs. question

is open. Your line

Graig Suvannavejh

taking X. for maybe questions. a Hi, few good my keep I've two to them morning, to afternoon, or Thanks or I'll but try folks. actually got good

opening you First say just apiece provide there we commercial other around opportunity seeing or thinking should color revenue be your they're can lead at equally three comments $XXX on programs all in if any $X.X the perhaps billion your that? million magnitude how sizing about of is for terms

is model. color for will around cash first be My and you're continue Thanks commonly that the Thanks. geographies think then about U.S. year steadily and year? half half fourth second is just think into evolve about toward expecting in the for or from how the should Europe pricing? my to quarterly it we increase the your burn rate pricing as see burn should similar more or quarter. has will Should increase being half we and cash But focused question that we in second subsequent Frank exit around what we less OTL-XXX versus final we question assume And beginning two first given Europe the of price U.S. how second the in just between launching than to the we of the in be the quarterly

Mark Rothera

to over with two start the I'll then So and Frank. hand first

lead incidence for the You the ask annual about revenue opportunity-driven more three $X.X programs. on any color billion opportunity

But look you I color And is at is think indication at given it's indications. reasons when does also guide account that a a pricing pool the upside well. the of And you ourselves It each we've into then And annual and largest go prevalent therapies about expecting least $X.X global is we're at WAS. be indication asked it's look of more higher to be actually gene our when ADA-SCID when color we could important the here for number you and at MLD incident in current approximately could those therapy billion collectively minimum. on XX% those around three markets patients which prevalence. can the incidence very about really in you the reminding important analogs a indications So MLD that an a WAS And not as see I incidence an gene eligible for and opportunity. that as ADA-SCID key for the basis. using in then a of world

think I remarks. the to Frank in alluded that prepared

a could for is patients expect with a We of sort gene And has a of that syndrome therapy. need progressing for XXXX those be to worldwide that prevalent about Wiskott-Aldrich pool. eligible which that condition slower we with XXXX living significant estimate XX% living disease example treatment. very So

see see concerned at think launch. in as Frank regard ultimately prevalent a with balanced this a we we to I eligible MLD build XX% treatment. we alluded incident. revenue So especially it that would pool the to roughly both is juvenile an that With as far for as the as as would an population but incident-based prevalent be think But that in approach incidence be treatment play

given But think options. I there very second which well launch. on I a as Europe be pricing actually with the we MLD Europe many then between U.S. case we've are you I or we generated start need fact to in get reasons of There I and a unmet both Atlantic. to said are about there's And with. treatment pricing launching first relatively the be compelling And are the for think could the response is will sides Europe pricing make that is year durability set that another tight a OTL-XXX no to and of U.S. data very we the payers So, think consider so high point severe of the because talked think that course to the this before as disease. corridor have to

we'll be learning carefully will ultimately watching we the the time launch. and take U.S. that to price U.S. on in listening view closer So a

the So it hand I if you. over Frank can was over to to question you third

Frank Thomas

Yes problem. No sure.

for MLD. So sort growth ramp in to the would growth as year think it And some U.S. of in But would say opex start QX. spend growth in sequential if generally up U.S. of commercial of about of half I for I inflection quarter launch think the we potential on top the come for the a I quarter. in there's be on XXXX the on an there incremental I question on second to likely the modeling Graig incremental within say just the preparation wouldn't mean

in construction be $XX previously we've will terms XXXX and In because I facility CapEx which total the think $XX is which earmarked million CapEx spread we'll the piece XXXX on the manufacturing other to about of over million start XXXX.

I of XXXX first construction second the half activities largely. will and half up would XXXX say So ramp

with would So associated that's the facility. I the how burn model and CapEx the manufacturing


you. Thank

from of or comment line Our Cowen. next the comes question Yaron Werber from

Your line open. is

Yaron Werber

Ron, much might taking for thanks very actually. the two question. Actually I if

question think the And me considering commercialization. on to the ADA-SCID how X-CGD also just importantly and the and down up the as moving we really might of slight how quarter-over-quarter think programs X-CGD data filing mostly when Strimvelis Europe for I particularly first kind kind between staggered thalassemia other whether therapy about think sales. then next on launch you're have on and Thanks. you forward drug So wanted regarding the we more thinking approaches a about just and a and timelines as you're just And briefly regarding touch well. U.S. there excuse of I should

Mark Rothera

been vivo It therapy. Strimvelis product. great Milan about in is in center for Italy. It's world one has So available a tremendously learning a ex us the tool only helpful gene in

transplant the bit patients. depends be learned so country going what well-managed process staying extent help lot cases treatment patient to one know we've cells as which think say for where I gene that formulation And only important a you risks forward for with treatment. as is marrow gone in traveling. modified one to fresh bone or programs going the process. about And those from that we've some of have stages from what bumpy center patients patients let's of little a it Italy between Strimvelis and the yes to identification cryopreserved to through the helping available it then center in various stem make of fact do is the entails in and takes another distinctions is on locally decision making through so the move going over our of Milan the a to And many a And go means to patients to that treatment

forward cryopreserved a that which it lot really to our As with most along going for patients going the we do those stem cells easier part gene for to make modified is journey. cells travel the it's look this are

is think beyond. launch for I this used message learning a overall prepare and as we've tool ourselves the OTL-XXX again to for So our

for maybe you So question? the next could Bobby answer

Bobby Gaspar


X-CGD as two and beta-thal is as are as far similarities as far Yaron some programs. doing there in concerned So the those work we're

complete. it and But you many as focus as proof able on adults well. X-CGD pediatric that of want seen. late is order thoughts to best in were was results for patients where on adolescence as possible to as the know So study And initial concept really would patients be the treat pivotal our the treat we to

to see so this pediatric patients. need And outcomes in year we

So get is that's that year. large But thing of that for and process that of a this a appropriate is population about the talked we've to part need so number is work this manufacturing other prevalent treat the we patients. to

the spending of So time fit enhances ensuring year vectors. is that of the use are to the process on we optimize a again commercial transduction for that and use this manufacturing involves for opportunity example

condition order doing concept really as at as established well. is to well. and also the what in say And get I vector of that transduction population drug process CMC that's patient in be both opportunity part looking able what ongoing process So to and Proof far again to latter as trying we're product as correct that again the and as And is is at of enhances beta-thalassemia manufacturing looking opportunity. predominantly concerned. that serve large use work is that third

So question. that your I hope addresses

Yaron Werber

Thanks guys. very much Sure.

Bobby Gaspar



you. Thank

question next Nierengarten from of comes line or comment Securities. the Our from David Wedbush

is open. line Your

David Nierengarten

the births the the And be be a and prevalence. MLD thanks incidence versus probably course of asking because question. that so those patient. blurry diagnoses And know some new taking might about incidence little Hey, prevalent a numbers of a I had diagnoses? there's strictly for counted are numbers or one patient might by I on and a bit provided line new I'm actually a as diagnosis delayed you but

just detail Thanks. on those could little was you estimates patient wondering for a I MLD. provide So if more bit

Mark Rothera

Okay. just your make understood I've question. sure I'll

number. So constitutes you're asking annual incidence what rate the

David Nierengarten

completely there as if that prevalent about bright annual a think incidence line patient. and a Yes there should we then Yes. and patient were down there versus the separate if of some was drawing then

there is small Thanks. overlap So degree sort of large or of or none?

Mark Rothera

really looked XXX across the with we've as patients countries we've at And So the orphan a condition. year with the that signaled invest drugs. MLD to XXX rate incidence we

that form would to really launch actually. of treat. we those be blurry XX% the patients on side then treatment some MLD possibly we've a it the indicated adult could think on is have symptoms at on diagnosed not eligible think prevalence Where extent later you for as that because I early know the little are becomes about juvenile some of based that until we

they So missed may be screen. in the

the in blurry adult pool Which large line by we'll over work. the we being as proportion. to label adult form. And XX% prevalent potentially the is able the that form. there are So address also prevalent potentially a expanding in they a you see be pool time and about with some estimate can further of There's doing


you. Thank

Esther from Oppenheimer. comment the or comes question Rajavelu next of line Our from

is line open. Your

Esther Rajavelu

guys. Thanks,

versus being be able I would ask apologize before. for OTL-XXX. for what I are the the how the U.S. I'm guess not requirements EU trying for the to files for Sorry file the question understand to

Just trying to understand the delay.

Mark Rothera

actually of just the And what year in a do I we XXXX. strong filing. European in Well the place early or this step really that next the we're meets end first And of their have developed that half the year that by ensure strong to to the requirements. we believe to expectation really intending we're this is we're a with that our with in is launch which meet think planning package FDA we for to

crossing just and filing we need with So the this of year. we've for it's got the what the really checking FDA off that half first in

Esther Rajavelu

you. Got

so information just more more than different. the it's packaging do So to anything needing

Mark Rothera

really meet we to that in now need and meet is but just to with understanding everything their place our the check that is everything requirements. going have we that FDA we that Yes to have through go

Esther Rajavelu

Okay. Understood. supplying And also market? then be the U.S. will MolMed

Mark Rothera

Yes it will.

from Frank As available California. in will to bringing on stream that we're own alluded our facility XXXX be

experienced very mitigation. in but They will commercial ensure U.S. locations both have are also working will to we MolMed. be optionality launch in So capacity through partner. give to with CMO being probably And we time able and we good ourselves the as with risk so redundancy now provide to

Esther Rajavelu

my Can the then you remind us EU last question. what And right now? is Okay. Strimvelis for in pricing

Mark Rothera

around per it's €XXX,XXX patient. EU In


additional the I show conference at like in remarks. Mr. turn the I'd time. questions Mark any you. no over to queue to closing for Thank this back

Mark Rothera

today. the call Well you thank for joining you all again of

patients I patients we around tremendous therapies benefit to these believe our toward do administration. to And lifetime world. intend bringing we're the can think making through potentially we as single to a that curative these progress we get in provide mission we approved if

year it XXXX is Orchard. mission. for be tremendous And promises a a defining to So really

year momentum approvals have Our XXXX. continues into only to we potential launches and to build and not this and but forward year into next to look

look thank for forward I soon. catching again us. So joining to up you