FULC - Earnings call transcript Q2 2021 | Fulcrum Therapeutics, Inc.

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Operator

Good morning, and welcome to the Fulcrum Therapeutics Conference Call. Currently all participants are in listen-only mode. There will be a question-and-answer session at the end of this call. I would now like to turn the call over to Ms. Christi Waarich, Director of Investor Relations and Corporate Communications for Fulcrum. proceed. please Ma'am

Christi Waarich

of Good our conference operator. during welcome the development may financial the to call Act and Litigation Thank XXXX. timelines, expectations of Please morning. and be Therapeutics These meaning within statements call. contain statements made Private reminded Fulcrum Securities may Reform about you include forward-looking And the future that projections. this clinical remarks plans,

as but not representing represent statements views of be our Please future. relied our should may an in upon not refer views While these these forward-looking so. on We our and today's filings With today, as Securities most to the with and uncertainties Moxham, we in are statements they do taking to for call Officer. obligation and update the are with the Chief a Officer Scientific our Chris Stuart, Chris Executive me Officer; Commission Morabito, Chief business. Medical President certain Chief and on recent Exchange associated Bryan risks discussion of future,

me agenda. run through Let this morning's quickly

the my data, Bryan. provide to review Bryan Bryan. and going news, corporate volunteer it's adult next Chris the on phase review turn XXXX begin today's our Q&A. updates will call will to healthy Given for to Chris of Bryan programs key the over open from deep and call pleasure Moxham with one the will the overview FTX-XXXX a preclinical that, With and will a call Morabito a clinical results the results. calls focus quarter. we're

Bryan Stuart

clinical that programs. trial, progression, patients. strongly dystrophy phase from disease for show losmapimod in both past patients positive slow announced belief And function These support today. the In quarter notable to approved currently and were form results June, muscular has and thank particularly where the that Christi. you stage FSHD, everyone. we our potential effective a able for to This Thank of but in ReDUXX you, treatments FSHD be and significant available. for of our progress Xb we severe improved us Good was safe progressive morning, has losmapimod results the no with the therapy joining

promising these the of discuss XXXX the half meet in with potential data hand, With from in we second next to to FDA plan steps. ReDUXX

FTX-XXXX to are report today, compelling from healthy to volunteers. one we ongoing results trial Moving phase pleased very adult our and

introduction you of sickle the many successfully that cell target treatment that can therapy cell disease oral cause know, for represent sickle the advancement. therapies target As a The major disease of landscape of current only would select includes an symptoms. root

results in as We excited both induction trial, saw are in the impact efforts especially about in terms the from we of fold impressive X.X hemoglobin fetal the an as In induction hemoglobin mRNA see mRNA. and tolerability we increase fetal this ocular sites. of trial, this well of

to observed the would not to generally daily a indicates hemoglobin also well the care, standard to been also And threshold of in carbon to and support research pleased tolerated fold be of induction able hydroxyurea We're We production. predicted FTX-XXXX two these sickle preclinical be but saw our and exceed two Encouragingly provide HbF current that meaningful pre-clinically. oral results benefit fold on patients. to has induction or mechanism. FTX-XXXX is share the fold three evidence biology X.X we cell achieve provide provide HbF also pharmacokinetics proof first three to fetal to we increase these results particular administration. the only clinical extensive that may engagement. size, to-date maximal once which Building achieve superior This

has sickle platform, and initiate to us defined disease track identify cause programs an Seek our differentiated is of in approach phase the targets year to rapidly in modulate will discovery by a diseases. end note unprecedented high Seek novel rare the scale Fulcrum on in from cell hand, cell results to discovery to drug to efficiently non quality XB root in then development target enabling that and patients our Fulcrum the the innovation opportunity our identification we XXXX. pipeline. these settings, of that which plan allowed both our initiate at a powerful drug With came of a unparalleled and clinical backbone hemoglobinopathies genetically I relevant By of in company creates sickle trial remain grow

work of doing INDs quarter by Fulcrum at will new to to the are expect we We XXXX. submit first the Seek enable us

enabled Seek addition, continues to both which well. proceed collaborations our Acceleron with ongoing In has also Fulcrum and myocardium,

see, about the updates you expect have that, we to research quarter more across key With collaboration continue with and to us term. near cash development our meaningful of multiple our with to initiatives into can first work programs, Moxham important runway preclinical and platform progress the from that call clinical As the FTX-XXXX. discovery speak takes over in to we a make Chris turn I'll XXXX

Chris Moxham

cells shape. Also, red red often cell sickle or blood shortage Also sickle causes take blood is circulation Thanks, the as sickle type individuals flow. blood mutation prematurely. cells genetic of most characteristic known cells disorder die efficient cells the with Bryan. this red disease a cells all biconcave, carry in common to on in and by red of VOC. hemoglobin XXX,XXX small inherited United a the disease can experience the blood an Sickle get an known and cells stuck States when individuals normal of which is HPV millions often enabling disease, caused parts affects anemia. vessels, through constant hemolysis, individual Sickle vessels blood as what worldwide. the blood In people happens, of are and they blood apathy, When crisis restrict vaso-occlusive cell body. estimated more is cell through gene. or blood sickle to and healthy travel a a the oxygen In It red round

suffer arrow, But and promote by such sickle These and to hereditary as the like functional have morbidities HbG can pain need clinically sickle crisis This unmet both the are therapies hemoglobin is Using Fulcrum of to reducing mutation, levels baseline for observations along of two impact root is cell mark discovery disease complex. cure. serious been Seek increasing our progressively HbF histone epigenetic Beyond of anemia we molecule inhibitor, inhibition provide acute mechanism spectrum similar from cell and that have stroke an trimethylation of a underscores decreasing HbF asymptomatic population. reduced and disease XX% robust often and addition recurring to have in that increased this EED fetal patients shown highly of chest thereby histone the HbF between X% Genetics other asymptomatic the plays thus levels Current three of and Fulcrum well mRNA HbF. that to of sickle present I'd potential broad and impact hemoglobin, above PRCX or People patent protection remains genetically who disease. as a and likelihood significantly of that including out implies mortality, shown decreasing suggest complications HbG fold provides levels show therapeutic also and red levels such can events diverse that the target Together target that VOCs cells. protein an drug the transformative associated potent this and symptomology properties address Human achieve effective PRCX can with these biological identified blood that protein tremendous with and to clinical FTX-XXXX has that catalytic expression. a issued propagates above hemoglobin. selective non cell fetal as treat trimethylation It mutations capable until baseline. a of with also additional blue and PRCX XXXX. that presentation. people living We like syndrome. levels that novel disease. matter or are elevated inducer expression total HbF are is were HbF subunit typically drug with are which through lifespan. on platform associated the of composition persistence EED, outstanding profile. off induction. a EED is PRCX and the as oral highly typically clean XX% point We as potent HbF a cell cause inducing a this benefit to may capable induce mRNA clearly binding has individuals HbF The in rationale small HbF meaningful unable EED levels with developed provide disease inhibition sickle carry FTX-XXXX in therapies

a observe of models. and and models, in consistent have vitro fold We strong mRNA three sickle healthy cell to protein observed XXXX In and both HbF and preclinical correlations disease we expression. profiled numerous vivo two between protein we across induction in

editing. right, mRNA target of this two concentration showing with The As and that we from protein increases connectivity Townes seen to are highlight the HbF and CD-XX engagement fold and cells protein. of model three healthy of positive consistent mouse the mRNA correlation In data HbF HbG dependent on in changes induction HbF we protein to-date. finding results reported as similar FTX-XXXX with preclinical consistent of generated induction that studies inhibition we mRNA to throughout the observed compared also gene the and EED is of in those set preclinical with expression a levels very

HbF maximum derived sickle cells of being X donors cells demonstrating publish now and erythroid a fold approximate an from CRISPR and positive trial. therapeutics, three CTX-XXX, cells, from CDXX vertex in donors. positive a a by CDXX from three editing in data in HbF phase induction is healthy BCL-XXA X, XXXX cell approach healthy gene achieves FTX- clinical studied This Specifically induction fold similar to in two

to were provide X% levels post baseline FTX-XXXX and meaningful oral has we've or In with cells the cases, this increases increase robust amount observe left pill. two FTX-XXXX. cell we sickle clinic response and of characteristic treatment HbF positive absolute curative three cell in donor But the benefit potentially and between HbF and even to obtained as into values slide, translate these all once sickle the of as equates potential XX%. a can If see increase trait. fold daily the On healthy of HbF CDXX donors a to from have above you to side a to that who we the were the that profiled administered had treatment

small payers. we of oral preferred we the could providers think and an the believe induce three to about levels value HPF patients, option that can treatment two for be As fold this molecule proposition

small inducer them oral as cause As or treatments this disease HbF sickle strong stem I of typically on scale potential with modifying, disease with and Based oral cell cell be we can symptomatic landscape. inducing mentioned, administration body cell benefit therapeutic a addressing HbF XX%. the sickle transform of has address in distribution cell may population, conjunction the disease. root baseline the literature that X% gene in believe used editing pathology the sickle medical transplant HbF such treatment at molecule disease effective to broad symptomatology. to levels meet FTX-XXXX of patients today, and contrast to generated In are and convenience global FTX-XXXX with a patient truly for of need Coupled potential regimens

we've healthy You'll particular exploratory trial, see volunteer in that that mRNA of in measures sites. HbG our phase one included

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the XX occurring digital context into assay the any that begun newly HbF the increases take particular cells of see, day As HbG will context robust we change changes HbF on day to to particular Also, in of of XX HbG protein. as narrow utilize window measure a specific these HbF to translate highly any which to sites This We if mRNA opportunity the enter are may in circulation have measure droplet exposed that we be PCR the to differentiate of two sampling. site first approximately mRNA to represent sensitive and a determine a Thus, mRNA. to quantify immuno you can develop particular quantify any and detection time sites study. relies from HbG weeks trial. protein provides in early

impact Fulcrum, potential on at discovery Chris? call hard turning people the I'd fantastic It's real to innovative a the Before who's team volunteers cell to and Morabito, drug program, Chris has who in sickle to make like over participated the the this in disease. so working trial. living that example thank this of a with

Chris Morabito

clinical will our take that the healthy be ongoing we Thanks, sharing Chris. from volunteers. I'd like and everyone phase remind one results are to to moment a trial

evaluate treatment. the As particular collecting in of is tolerability data phase target are a safety, the protein. HbG The contain pharmacokinetics reminder, which aim to also and trial increases to and particular levels is ongoing engagement that X pharmacodynamic HbF sites assess of FTX-XXXX mRNA sites,

Here the the lower FTX-XXXX X. completed modeling, all target be being MAD design and no generally effects events this we treatment XX was doses These cohorts SAD determined expectations related effect are was originally you and stage. no events Based half There studied demonstrated which the which engagement observed cohorts MAD emergent cohorts. data. the and believe the X engagement and SAP one trial. greater of XXXX were the to lower with grade can be that also milligram advancing and safety completed unrelated we drug. in PK/PD cohorts through the pharmacodynamic proportionality TK possibly target We've and tolerated that in six and X, a trial SAD both that well the and derived from the thresholds expected deemed profiles the support and SAD There FTX-XXXX discontinuations. those modeling this on milligram data is expected would were directly modeled. cohorts, at effects engagement cohorts. in the doses. and we see pharmacodynamic adverse and of longer included All exposures in This date, preclinical in to least mild we SAD hours, To serious through XX to have MAD X observed MAD MAD XX at target was X adverse pharmacodynamic MAD doses cohort cohorts. approximately consistent to than and in what across resulted influence mean had was X study tolerability and seven at life

we clinical was at day demonstrate after in grams after was that XXX about treatment. maximal by we've preclinical target from will demonstrating trimethylation demonstrate epigenetic inhibition this mark is All directly the and the These a slide cohorts. achieved share phase a on XX of engagement the Overall, facilitated The inhibitor histone in subjects last one three the maximal trimethylation. our Next, Shown these engagement PRCX note histone that day results days potent data engagement levels X visit endpoints of baselines denoted X exploratory trial. as also measured robust key at as these SFU denoted We engagement baseline And FTX-XXXX XX with data X samples We which of potent XX by consistent retained the dose PRCX. up XX samples achieved and results engagement results collected of of target T-X. follow milligram generated. then that the XX. activity. target XX% of and occurred days on to measured treatment. X at collected consecutive at at safety Maximal target target

share clinical resulted demonstrating both data. HbG treatment mRNA in the mRNA dose HbG and and time dependent we will increases of proof FTX-XXXX Next, biology.

these induction days. and significant. not the and HbG X.X observed in these XX evidence panels, evidence X proportionality. presenting mean milligram effects that statistically X induction X dose fold milligrams of significant There plotted but mRNA the each we point. we're At is induction XX both a SX mRNA milligram, over cohorts Here of milligram statistically the after those clear In placebo induction, there achieving X is and milligram time X HbG at pharmacodynamic XX cohort XX cohorts, fold of as XX MAD are data milligram

induction to up highly indicated cohort the mRNA I'll of milligram out You can milligram see response XX as statistically in the Encouragingly, maximum a induction the X XX fold that X in interval getting range. cohort presented from baseline. HbG changes the confidence is significant results by also XX% demonstrates durable. all also the and we're of point

to CT Townes You we that mRNA model. after expression observed we've treatment protein as days subjects period, HbF type mouse what with the demonstrated maintained at and a HbG pre-clinically will to which X day of translate is well. follow XX also notice consistent durability the believe the XX, up This induction

cell for on, fold predicted we meaningful we benefit to induction. I clinical HbG will that with sickle evidence dose To remind you mRNA note fold three that that we remind protein proportional mRNA the results where effect. these Before multiple is two of across an I'll strongly induction reticular induction Last, want contextualize models potentially protein. induction. we will of that also X.X move F-reticulocyte pre-clinically each I you suggesting meeting a thresholds the also observed mean to against to PD induction are the HbG results HbF this a mRNA patients. present provide clinical site exceeding contains HbF and F-reticulocyte a was correlated pre-clinically,

after treatment FTX-XXXX cohort increases HbF the safety translating the not is HbG X.X F-reticulocyte that and a day induction did increase fold the induction both been particular XX strongly we sites demonstrated milligram which statistically at in protein treatment observe follow increases to-date. correlates persistent after observed X milligram and While periods X XX milligram mRNA up on treatment. observed have cohorts. with XX HbG the mRNA the significant mean We indicates XX days cohort and and

results target As XX mRNA we the between endpoints by PD the sickle target thresholds cell with demonstrating XX Extensive that induction summary, literature days. demonstrate the In a to to engagement meaningful presented clinical robust to setting. two expression a a patients. results We observed volunteers X healthy the protein XX HbG three and clinical broad to in and disease to as provide fold target earlier, indicate clinical by expression and induction These laid individuals. today consistent of out healthy and genetic maximal kinetics HbF day by protein predicted across are the [Indiscernible] protein translate days, engagement, and potential and induction benefits HbF these relationship F-reticulocyte engagement induction observed meet mRNA benefits.

highly These mechanism. HbG pre-clinically induction also clinical of have HbF are and correlated. We demonstrate mRNA demonstrated and protein expression that results proof biology

these the Additionally, correlation and demonstrated based predicted the to certain based of induction mRNA is X.X as could the If continue F-reticulocyte sickle clinic, pre-clinically well believe HbG results to strong expression we mRNA mRNA in HbG benefits protein clinical provide date translate between translate FTX-XXXX mRNA strong protein cell on as mean the patients. we observed in between to predict correlation induction clinically. and the HbG fold HbF to

next for the one what anticipate In abstract at additional trial year, at the we terms of we sharing from steps acceptance. conference today. on a program, ongoing the reported the medical end of results phase Based pending

of milligram We also a cell would quarter with results the and individuals cell up be proof period treatment of concept of with sickle on intend demonstrate dose three year. X to fourth aim phase trial in our confirm disease. dose in clinical designed XB It and in the with patients include The early trial this will involve multiple to a start sickle to build months. an current to

We clinical are be XXXX. that study planning X/X will phase start the trial that will subsequent a in

including we to non clinical to turn disease by the that, you, IND Bryan. I'll initiation to-date back end sickle of the intend support a and the results clinical hemoglobinopathies, year. trial With an addition, this of In and submit it beta thalassemia cell

Bryan Stuart

of forward about results a the cell very potential And of results a significant excited treatment preclinical therapy patients today first clinical enroll the plans in years of by has bring that Thanks, opportunity the advancement daily in protein, the with Chris. These sickle the have prospects and we to HbG increases compelling F-reticulocyte are end increases need, is presented results And our disease be our for in trial great on mechanism ahead. potential also a data shown These the our translating HbF bolster new exceeded cell the that product two and we've identifying where in in expand prospect. additional to-date. provide to expectations people clinical we programs proof generated. understanding the biology provides with We're the great to cell mRNA year. our exciting FTX-XXXX very further to indication disease, The robust data a our unmet believe and living sickle to programs sickle from once oral in with FSHD to engine. look we diseases and

expand look the updated to pipeline. you seek to We for months we development forward on open in questions. the As you keeping Operator, our ahead. now our progress may line

Operator

first Ted Sandler. Instructions] you, question Thank the Piper of sir. line is Tenthoff from from [Operator your

Your now is open. line

Ted Tenthoff

thank you cell between anticipate there that patients? think It's Remarkable from Again, is Is thinking this that seen migs But And and about so haven't modeling just very see any much. a you differences to you healthy sickle great or Great, either work the what appreciating to from results. the might XX do and any in we much. data. worse better yet. Thank protein there congrats. reason patients?

Bryan Stuart

over we Ted. XB Chris little there. Morabito what I and it can study we Thanks and speak seeing to the more anticipate to Yes, would turn a phase

Chris Morabito

Ted for question. the So thanks

was question trials. the mean milligrams. about clinical I first assume that you Is The ongoing correct? XX

Ted Tenthoff

Yes.

Chris Morabito

you. Thank

first, I biomarkers. think by that So go the just PD we

exceeded. think some to the get difference be the that. all There induction differences see don't in I but engagement, increased. engagement in not And think exceed will to maximum mRNA a I a we'll that will might limit HbG target could maximal maximal target again, we achieved. engagement We've amount. to likely to already we've be be three the at get will target kinetics doses. the exceed achieved kinetics we

increase over will currently of today terms at especially in but we be kinetics. that I expect point. this can't as be And predict an what an increase, what F-reticulocyte, would have similarly with we that will we there see number would expect We

that time of when the So course will happen.

look continuing in we forward continue as so we're which that, with XX a that to XB far goalpost move in induction, as result. seeing to the And very forward three mind about meaningful over thrilled fold the what regardless milligram are, We to into study. X to what predicted us we phase seeing is two we

said might patients that volunteers. our to see we increases what from about ease cell was patients, our the will to permissive, induction Having in of in see in it's sickle based health compared on the bit to healthy patients. shorter see of what compared question which more is what induction that expect disease, equally know seen have is that, where second sickle likely models bone same Your ease. in we or where patients human increases marrow amount would more of preclinical we the fold we're faster least versus RBC pathology in this We to we quite expect half-life and a because more significant robust cell at seeing health demonstrate preclinical changes, just data potentially

course, later year certainly share starting as is of and be forward. this this the results on XB excited to they the Of that study we'll come those point will be

Ted Tenthoff

Great, excellent. Thank you guys. Congrats.

Operator

is Your Ha Stiefel. Dae the next question from from Gon line of

open. line now is Your

Dae Gon Ha

drug, or the patient me and as given of this But to dosing you and for what just But phase on two administer you mentioned up that questions, on guess the next to kind fold. are plan our follow magnitude I from can for wondering, thoughts that's just study. three congrats the trial treatment chronic expect well. your the Thanks oral taking MAD XB likely

safety then part kind chronic going second is, saw we a what guess, is little that X more, given question can the to you the that? expect to basically of And on dosing, this I signals provide that or should volunteers bit healthy tampering that should with you. given guess, epigenetics? bookends forward, Thank the X.X we expecting be So I around we

Bryan Stuart

and we're on observing Thanks, just we've over two again, can that And that One to hemoglobin fetal then cell is relative into we sickle question that can Morabito Dae observed levels what up increases Gon. Chris a from to have. it perspective. turn break safety comment I starting you tolerability patients realizing the most answers.

Chris Morabito

so thanks. Great,

indicated, will XB be to will chance And excited doing that study. see of in phase really that. to be effects patients. an our as open this the We're drug So first label

ultimately, effects genetics, rate, where for this study. what can and XX% with be percent we'll get up to we progress we of do in So of is feedback and expect HbF But The somewhere be a setting answer, percent, patients. important the target on to to a like relatively the Patients new, will as would know to roughly is potentially able see to XX%, a is other which would disease, goalposts two patients sort induction. as Bryan intimated, a a study get clinical on cell data, threefold want between we XX% level sickle increasing to three start clinical X to XX% we with profound where based see which by get, magnitude and to XX% changes. as

the would start phase could potentially but which study. You even in observe certainly see XB, to QX we expect to in future the

the we're phase well X so really based this not has quite actually tolerability very tolerated out ducting, seeing. pleased on This date point is the and two these safety now seeing results, is what we're over a far, of on a and into with based we're the you perspective of they'll pharmacokinetic period a time, but as from dosing, that patients the of of give terms we're In weeks kinds as while us were on chronic levels based results achieved optimistic moving and longer healthy. results that

Dae Gon Ha

are If chance may put be add just But a volunteers, these could some value? really healthy dumb one X.X more question. increase. percentage fold I question. you can This Any

Bryan Stuart

am having I hearing sorry time a tough you. we Dae, have

Operator

up have hear so handset Please been your pick on can speakerphone. you Yes, we might ma'am. Sir, sorry. speaking clearly. you your I'm

Dae Gon Ha

hear guys now? you me Can

Bryan Stuart

We can. Thanks.

Dae Gon Ha

But you exercise can quick mentioned in percent patient these the any just to healthy just target follow a question. similar a something XX% up the study. So do dumb was, this might really being XX% in chance be we volunteers. But

the Or or HbF? you've even you. get of out seen percentage that fold on question? the Do that Thank we four Now the is the induction? value increase completely

Bryan Stuart

sickle So yes, both like Chris turn is as from as would more what well we've speak Dae as I to to pre-clinically Gon, I it healthy donors over seen CDXX We donors. to can Moxham?

Chris Moxham

pre-clinically of as XX% observed absolute with is induction baseline. absolute pointed above levels out we've seen end Sure, have three of this so two And terms, increases certainly baseline. above absolute I we fold of XX%, HbF, in what again, to upper

sites. to been is XX day levels again, follow HbF that period the study able are to longer up healthy within highlighted, question quantify a In of not possible. particular So which need the absolute is we've of day of we and levels safety be And process The of has definitely context would focus towards been absolute really overlay context of longer as days HbF XX of HbF that And of context pointed the a the whether which terms as will quantify to study. that only the frankly in achieve XX dosing done typically of in the curative erythropoiesis, of duration, detecting a study associated a in using protein phase normal require in can we this the measurement study we with study. XB volunteer HPLC a a duration. effect. a then a

Dae Gon Ha

those back thank much very you for responses. in the I'll hop Well, Awesome. queue.

Operator

the line of Schwartz Next SVB question from Joseph is from Leerink.

open. Your line is now

Joseph Schwartz

fold efficacy you you that if thoughts to might your from very saw mRNA in two greater have you than expected Are any was expected? Do much on exposure the there you due based healthy other longer a more half-life contributed? you any greater in have work? due view well. in to preclinical three on purely your factors that's volunteers think congratulations wondering me saw than to and I why as Thank increases

Bryan Stuart

don't we Sure, as very that's to a question. today. any good why clear have And indicators

the example, still very in data for globin fold in model think, context mouse genes, a system, town's two difference showed operating again, mouse humanized three preclinical transcription notable perhaps between of under the the is again HVF. we or In, to which the of control I robust in the the increases factors. where murine is but the

fold going fully in be saw healthy the seeing the of differences to system that we that feel exceeded may have in the some and levels we're preclinical accounting for in of that Now, the study. fact in we're the induction humanized volunteer level

sickle induction fold permissive, remain as commented two very clinical this and certainly cell We baseline HbF that results. a sickle the and setting. provide into that see is are are we cells focused setting these sickle shorter translates benefit half any red to whether erythropoiesis life meaningful that more given we on be now the the we Chris cell implied and blood certainly with three Morabito the looked cell will levels pleased even And fact believe have to that to Again, elevated, know elevated likely setting. in that

greater context that think opportunity see a gives greater So induction. a to even whole us

Joseph Schwartz

when pan-cellularity. high to has and And That's into you that wondering talk I you whether very implications get I been that have to then, patients? developed able interesting. for healthy what have could was the you recall about are evaluate and if FTX-XXXX been volunteers attribute

Bryan Stuart

what pre-clinically. Yes, you remind And I'll we can of And to And turn it what we here. just over did we expect Chris. observe then

Chris Morabito

Yes.

consistent chance in cellular collect obtained a a the pan protein. high were So In again, very three context cellular based pan pre-clinically, would the from the certainly, pan data where robust to cells the donor a study, data to healthy volunteer greater cell induction demonstrated that expressing cells consistent of assess from to it's of two be the sickle healthy that. very able cells comment levels we're a HbF what And upon either induction XX% again, now in induction induction, really we'd we preclinical speak we to of setting. very did volunteer study much be either sickle a fold and have or very not of CDXX in where the donor, healthy cellular cell to and would context see that the were but observe a derived is

Joseph Schwartz

your expression to pipeline, through direct be biology more similarities and/or there your question. just approach a you do picture the gene than in implications on the the bigger if work are I could broader What then, of in there based any this And on programs might the development in platform? other where others way? think Seek particular read ask Fulcrum congruent Are modulate

Bryan Stuart

Thanks, for we're and being data, obviously, this very Fulcrum of Joe. Broadly, FSHD both the data in validating our and approach. enthusiastic, terms Seek about

identified these to of we that in had created very of we we're able Seek use we XXXX, medicinal see the own that of FSHD license. and in talked and excited we came Fulcrum this the that matter both about one as were compound So about, a chemistry other our the programs, them engine, target out chemical

type in itself and be we like like area. additionally, validation. expertise as with Fulcrum feel And other we I the hematology about other feel XXXX we We that we're as select an very So to Seek building think hemoglobinopathies commitment we're to great into is We're programs really would and of feel like the this that the say excited really taking referenced and lend of remains area opportunity. brought well. focus, in as

Joseph Schwartz

congrats. Well, Great. Thank you.

Operator

question is of Stanley. next line the Your from Morgan Matthew from Harrison

open. now is line Your

Matthew Harrison

I things want to I morning, a guess on. Good couple touch

others doses wasn't dose know asked range. just and I It higher clear about me. to So have

So about and next look happy guess feel expand. that's take do maybe ask to I aggregate XX Is you're just study? going or And change. could you at range, of expectation then want what question a your or into sort to wider dose cumulative the if I with migs a change you to secondly,

cell So longer of a of healthy you've would dosed time expect larger sort short get being to in and for what the time sickle than of over seen volunteers? period improvements you Thanks. patients these period in

Bryan Stuart

about turn we're and Matthew, in dosing Chris, XB we move the the over and well Thanks could thinking change. to talk as about to question to as second how

Chris Morabito

It data the that study milligrams on doses pivotal three Xb today, for the the the could six still XX want information be be milligrams will that to on choose the so from that we to LT phase At milligrams, reviewed study in study. will two two study, dose the intend phase be six based In dose XBv to first up determined way. label as we could data So the second I months. the upcoming and for we dose haven't we that milligrams, yet said, open running. one may volunteer select come it give that's study. ranging the potentially for in dose We XX those based us will

range we in of can't of robust end dose, yet the the initiation get a as PD doses take of we'll we the build the and on and with So responses broad would give comment a the we select that Xb model range which can us broad PK will approach that we'll that the as move make be. dose And what But trial. that's study the closer upper to dose forward. determination

changes, doses fold stick Now, either patients at in and that we've any sickle of our be and three that I to of we Xb two see oral goalposts especially phase the over us course, the a any increase in terms the an we doses to of to we of protein be again, cell saying given when have this increase or the been is here what would three increases magnitude before, Brian would levels. transformational, But would of as study, that, two that Chris to be thrilled and mentioned in fold medicine. reiterated HbF particularly test

Operator

[Operator Instructions] Your is of from from Tazeen question Ahmad America. of the next Bank line

Your is line now open.

Tazeen Ahmad

Okay, good morning.

Hi, me. that's guys. think I

Just questions wanted to clarification. for ask a couple of points of

then the that increases and up? HbF just of in couple results report should of follow we when see a have clear, so So I'm expect protein, to a

Bryan Stuart

we next Xb plan And providing of the an plan we the on year. second So of begin in quarter to fourth quarter the of trial this year. update in Phase enrollment

Tazeen Ahmad

treating of ideally a certain what you certain from impact can And just the expecting amount time, us would it dosing today? immediate then, would start something you then remind level long time? patients on how Is see regimen a be you're you to that of time would this And your take to the HbF? start expect or

Bryan Stuart

Yes.

as likely discussed, just in out process protein, we laid would for the to that. we protein to where and HbF HbF patients as first the we you longer the months, to It expect would see after three HbF the in quantifiable slide, time around be that [Indiscernible] takes the quantifiable So talked in a we about periphery. see be then month, be much more would

Tazeen Ahmad

our there respond, the And or patients, uniformly is patients variability.

Bryan Stuart

So, go in Chris.

Chris Morabito

we've the question, FTX-XXXX, healthy that have donor, what a whether that pre-clinically our tested that efficacy contradistinction a cell hydroxyurea, all sickle much or have increase in in robust donor, data. varied donor is to-date of to to preclinical seen that or donors we is Yes, from very they're derived much weaker sickle has a cell even that to more trait with response, context the frankly, and which

that So the encouraged very after treatment levels we're and very protein significant HbF increase fact we today XXXX. a in universally see robust by

Tazeen Ahmad

at entire you SAD trial question for enrollment? last on the me be that least based And for or population that would then expect would criteria eligible certain you would have

Bryan Stuart

is population entire this. The for Yes. eligible Absolutely.

Operator

from of the Frommer question line last is Credit from Judah Your Suisse.

now is line Your open.

Judah Frommer

Thanks the question. for

in indicate regulatory protein, be you've X% a HbF Just could today I should bar one forward, on improvement or that think above of I to that. be the you results past, in potential referenced competitor's well the path seem the mean,

biomarker agency any help that So with that thoughts on or you forward move another conversations bar, any the on perspective? a may either

Bryan Stuart

the in that What patients patients. referenced impacts greater an very have to up observed fetal there observing in increases the Yes. of hemoglobin patients increases to where terms these as greater of very which X%, hereditary referenced, about even we're is these from who bar human have a understanding have the just can fold I we've even be would hemoglobin clear say increase, they're from that on and would a maybe is fetal and is, of And small relative persistence on one asymptomatic. a meaningful genetics, hemoglobin, a you obviously, over point what fetal as significantly impact little essentially percentage greater.

So we're about that. very enthusiastic

as bring right to Morabito hope registration into X/X mentioned phase phase a and move to be to the patients this as quickly goal get then able into to XB the now, dose select is Our possible. trial as a Chris opportunity a trial, potentially to with

Judah Frommer

thanks. Great,

Operator

are call. further questions. you thank today's concludes that, There this for And no conference attending. with Everyone

You may now great disconnect. a day. Have

Christi Waarich

Goodbye.

Fulcrum Therapeutics (FULC) 10 Aug 212021 Q2 Earnings call transcript