I and Time need introduction, but that's everybody. years that. Well, is well another story. that to Pete, generous you it's on. now, we the much thank in probably good fact, another morning ] to And [ and add of to decade to very XX over indeed, experience March have might for confess
order But how course an because to generation actually, audience I'd unmet relevance remark a the ways having to the of landscape contemporary changed it's dialogue and our of over the need that we're in some contextualize to today. like has appropriate in introduce the
causes that's causes great not currently. that lifetime a rheumatoid it starts last all a So and going it condition. a chronic loss a deal progressive with is you'll accompanying of only arthritis disease function. but potentially, and of joint There's be destruction pain, It's inflammation cure once to aware very joint it no unpleasant
had clinics to were arthritis, our employment short -- Basically, a poor within Now died time. awful rheumatology, in souls developed and going life, a they prematurely. out their patients a full had of wheelchairs. when generation in rheumatoid of People They ago, I out or become quality came they really started lose very if of work. were
pathobiology which was Matters a X changed second of targeted when some of disease. first One was And more protein advances And years small about about. therapies much of the which over in pick key recent later this understanding we've the And the molecules. came the development reasons. targets. enabled better really concurrent came for engineering, the therapeutic chemical course, of engineering, us to years, allowed of had off development has
It than goodness. that this awful to structural certainly it's all can on tremendous quality in a success common story degree of Patients functional impact in this readily is here. life. have damage symptoms many hugely employment. are don't the but of have the on does shown to less a as so the of impact So same today radiograph see that happen deficits. as now patients do much been has the degree It but visible not But that the we observer reality to
systemic failure the population this And common autoimmune similarly that difficulty rheumatoid meaningfully chance this quite of particular after really adequate they're a responding any And exactly And the about to around the array about now, we have of effective. if is common others an you is the effective the have of most -- almost agent, expanded And similar therapeutics chance is first X% switching condition. XX%. of of condition, X% although response. all the have arthritis, the to of an is X.X% response gives treatment, don't to
that because not could perfect of at problem. XX% So the is a refractory it's patients they the all cycle, the drug. more that a on more point different through that in of often have And is happens left flip the we're and biomarker coin. you with therapies. argue to each a a you've hand, if chance some got seriousness, cycle advanced that the one impressive a we responding reality But what at And in level, get next responding just
a that increasing. in So population practice is contemporary is the issue size and this real of
have in role key in so last the might of that and mentioned So particular really anti-FcRn backbone our note that over I have cytokines, quarter begs why be and therapeutic very in century targeting biologics pro-inflammatory cytokines question cytokines. armamentarium to situation? this interest become there these advances really as the pathobiology to And targets the the and IL-X the well-validated form the the an of understanding CNF been
drug don't benefit/risk these with But also to. we currently has that of recently risks other inhibitors. a agents or somewhat co-simulation JAK we agents, will associated and nature the course, inform one the blockers, respond refer depleting will have different B-cell have more agents, which patient each different of biomarkers And ratio of being with reliably drug a to
is transfer from neonatal is circulation. name neonatal of the that, course, the to immunoglobulin receptor Now is because among Fc circulation potentially the the that the of fetal this and biologists protective know will molecule enables the comes the maternal FcRN you
or human And of global of this is FcRn IgG within environmental because of birth, So the proteins because some few of the months it IgG beings in protection the the most a abundant to aspect, first of a NG. of being homeostasis fact also from that immuno has variety for protein responsible cytoplasm But rescues receptor fetus degree in of of is pathogens. in degraded peripheral the abundant blood the the most receptor whole cells. one in
autoantibodies Now advantageous. that And pathogenesis, would face has of the that prevent if the receptor, process. this -- are you in situation you any would block condition to that the were in driving be the FcRn rescue
immune be diminish cellular respond a to of system would autoantibodies, another there'd whole the although disable pathogenic you of Furthermore, insult. because the not theoretical you ability to would concentration pathogenic the here advantage adaptive
pathogenic. that be FcRn. And course, ACPAs this long by are we've we a be any presumes interest that be it for that relevance also rheumatoid could affected would but rheumatoid IgG advantages we the can the mechanism, in rheumatoid there's role pathobiology known measure of there may majority the which in and IGM, arthritis, an in of the IGG of not disease. play and know, time so and also, there in But factor FcRn is factors, inhibiting rheumatoid. ACPAs But interest that's many about that's pathogenic And isotype of
at look let's more bit a So that little closely.
ACPAs. just it back X to skip slides, Sorry, we'll go
years So there's They're against that patients destructive autoantibodies so tunilated higher lot very the good and of are is. [ factors prognostic the over These one of interest rheumatoid developing to levels so. in XX good ACPA disease reflecting with rheumatoid tend in the And we not process so factor know ACPAs there or of factor a and antibodies. may diagnostic rheumatoid. But more disease. been be the activity auto last actually ] are poor also as of antibodies, initiating erosive proteins, it have whole
that [ ACPA The high. the And bacteria, smokers, those smokers citrinilate is is problem. ] a lung. with the there in and association may very be hypothesis is And the particularly certain this proteins, in
If susceptibility II system. allele at to that's DRB Class HLA slide. of the you referred have sequence the acid the top That's X amino right-hand susceptibility the in the
suggest data that joint they're rheumatoid destruction chemokines. signaling of in through some related [ modulation osteoclastogenesis in and contribute ways. the ] to by have occurs pain the they the arthritis also rheumatoid this so these about in X/X the to autoantibodies all antibodies. And presence of will we to part than anti-citruled of there's disease many increase There's system And these predate to clinical and can patients that data is of regulation And more we've speeches And proactive autoantibodies, rheumatoid be learned the ACPAs, one across of that of lifetime patients symptoms disease. in through signs onset play a but that decade. a a show arms find earliest of that in these of the fact, there's may rheumatoid, that antibodies, proportion immune of what X/X of right in peptide
and described and been patients have be I have the better related the let's to ACPAs. than one on exposure patients been production that biologic, of earlier doses that therapeutic for was among pain may that the many experienced they've case of treated chemokine remains methotrexate to generation ago, contemporary these And of had actually, say, may
So a ACPAs of have very in set autoantibodies interesting rheumatoid.
a And arthritis. group difficult-to-treat at so we there's rheumatoid by And mean so-called do to need look what that? of this undoubtedly
to can point mean will phase patients those the low to achieve unfortunately, a targets we successfully. remission. achieve of clinician's But remission view In status time. those or we advanced and disease therapy, proportion is what on then lose over from responsiveness go early is Well, very ideal treatment such small aim remission that a of half need activity inhibitor. do their JAK that of lose or not who to respond or will And time. either those of as an a over patients biologic to molecule, meaning will a rheumatoid, A
And because they proteins. with this huge in biologics, a particular, are immunogenic is all problem being
patients of And so leads About to that. loss effect to effect. the less immunogenicity administered XX% lose over first their will X sometimes years, of biologic of anti-TNF than even proteins time
really So where switch then not belief enrichment therapy, all who is of the active the that the over nonetheless, current era time, consequence patient disease. but move have have should when that an is symptoms to of is that and debilitating this you adequately to therapy an responding there's of course another mechanism in patients the of action very still is on
activity. it patients being prospects, course, able terms who destruction being call even of what patients And get having be of And moderate disease, work, achieving are work active relatively of the And some talk disease. those orthopedic on needing in increase simply low enough disease the likelihood to by the that cases, intervention. likelihood unemployment. it majorly of of cases, about might employment joint to highly be other increases we impact go may when of terms nonproductive in activity, disease, might of in to who to because we but meaning both of presentism, terms it be simply It active disease in but not can't absenteeism, in impacts and
It who impact get an And a difficult dealing because have of in has So has and health impact treat carers, all on become society and an significant on those exponential. the disease actually to broader their inadequately very families with rheumatoid individual. of comorbidities. has the impact controlled patients these it course, on care sorts costs
with do switch have therapeutics to is which So we best respond to patient array need to we of biomarkers from action And the the existing therapies. further might need that it, the problem you treatment if treatment us something don't really tell one of we about mechanism and simply another.
an give mechanism of there antibody of response we'll a pointers FcRn might got But with response. the patients point a that because anti-citrulated likelihood not who be a in a of may respond the diagnostic give of of likely some companion are precise most levels But action. peptide we've case inhibitor, those to patients higher to this that are
And already as nipocalimab. I study. which Chief Investigator Pete used a this alluded there's was study, called for been the proof-of-principle another to earlier, antibody
a administered whether an And whether was either placebo-controlled responders inhibitor. really in was relatively an factor do short-term It patients. that's positive was benefit exposure inadequate see the what designed at FcRn CPA number look there patients, not drug. anti-TNF to So idea of rheumatoid XX of to the patients, was or in small this drug. study with study And or was in a any intravenously to
its than in study but at ACPA, cohort we whole. some at those outcomes as looked higher nonetheless, analysis when And we median were with endpoints we a look really statistical looking when the that in the very at participants missed the plan, at primary striking other at the a But the ACRXX. endpoint, of a that actually there's response can primary fact, looking see
the histogram that You the can on left-hand of see this side in slide.
patients that differentiates and can the see response on the is all at if placebo. that the placebo look there between subgroup very see above ACPA, again, difference from So you comers left-hand side median you you this of in a at [indiscernible]. with looking And nice on histogram,
measure this endpoint we as XX would at change study [ absolute response. whole. Now a that that was ], in consider rheumatologists, to looking primary was the the meaningful as in DES and was really a meet which for outcome significance The very responses for that study statistical clinically ACRXX didn't looking be
is this But we'd in on right-hand type if of outcome ] terms of magnitude slide, to see of responsiveness, is the between we're here DASXX is of like CRP seeing IGG again [ or very ACPA IGM, that what is you difficult a outcome to a the of mentioned relationship now improvement relationship as that either type side look the ACR level, measure like CPA remission, the there's are treat to rheumatoid which which over the And and a most see the reduction of or we patients. there's I in striking earlier. would between IgG, whether as factors
and point So directly data pieces view striking of implicates of you fact, as And of vitro in heterogeneous similar key this relationship. one that is a of can the that different the a outside many sub from condition, rheumatoid pathobiology very see this probably in first have implication disease probably clinical that one of And are diseases a in the that of is drivers is fact, in this we've phenotype. subgroup there arthritis of that data patients. of learned
a is of those available attraction ambition most that's respond. the the FcRn who So are clinic, likely identify patients in but we've in that might got to biomarker
that We immune disabling the autoantibodies, but of inhibit without an other and the attractive symptom, possibility. have driving to is adaptive potential aspects also actually
at that look they really, population, can patient at reason here, might affected, we interest the are are that for our for shown and the look tell data population Europe. interest we the the of So the proportions in if size is be I you very a And I fact, but as are similar of that States United this the Immunovant.
around involved the that's call case phase of we proportion positive what quarters, is patients the to they particularly X are the of total when get the of that So autoantibody about disease. established
a of have if synthetic patients tends to figure response proportion over DMARD exposure about around up, go XX%. an targeted inadequate to anything, prior is And that who time. or biologic to The
what see the the that this patients disease. to is more the of And to more become. So duration, were fee the longer emergence higher difficult can and tends we treat disease
to therapies. lifetime patients therapeutic enormous in multiple failed also accruing despite who to rheumatology, number of So the rapidly my advance this we've adequately seen over respond
have benefits of through with just do drugs of life. present of they the we problem really, that cycle improvements drugs, in a this to number And At of tend but adverse associated next. quality effects do the time, various unsuccessfully enormous what might these the we incur without be
unmet the thought whole. So is globe, target addressable a Europe figure you around really the the I very is U.S.A. very a likely to right alone I have can as here and U.S. would in that in across probably there about major climbing, the would higher need let in say, thought see XX,XXX be And population a it's similar Europe,
of today. attention. through So the from I'm that make I you points your for Immunovant. to talk perspective really the hand path forward to going wanted those the are to Thanks And to back over Pete, who's going
