through program biomarker Thank related are mechanism to walk few pharmacodynamic clinical with underpinning take preclinical action MTAP interaction the directly key lethal markers everyone. The deletion. and to for MATXA a minutes you, Matt. Good synthetic our IDEXXX the the morning, you I’ll data. of pharmacodynamic
is of cellular availability hit upon As reduces partially one the which the modification which of SAM in SDMA, the MTA and this inhibits tumor cellular deletion, substrate, MTAP illustrated accumulates pairwise IDEXXX left, solid synthetic lethal cells, activate of in PRMTX needs the opportunity. XX% MATXA enzyme splicing in this that's two. The tumors, essential to symmetric PRMTX schematic MTAP happens which inhibitor dimethylarginine hit via on factors
one-two punch deleted pre-mRNA this selectively So splicing tumors. MTAP in disrupts essential
PRMTX MTAP-deleted IDEXXX which in mRNA cells. low doses. essential even SDMA IDEXXX competitive far and strongly MTAP on consistent in type to inhibition as is equivalent You limited action right, on strong in shown right, in cells inhibitor. high wild PRMTX in disruption the inhibitor, mechanism. can of SAM cells, by accumulation said the of even with cancer of MTAP full deleted The In MTAP with direct perturbs observed splicing same wild-type in contrast, cells at SDMA see has activity the accumulation be cells, of IDEXXX can't synthetically for that splicing all doses no very suppression the with Notably that
the of given and that's met the mechanism SDMA of abundance And the dependent from PRMTX measuring drug in in our cells PD. follow plasma, of by PD. this inhibition tumor trial, SAM of peripheral -- inhibition That's we follow tumor So measuring methionine action in of our by extent on concentration cancer patients we biopsies. we
biopsies, draw. with next tumor kilogram. workhorse, as matched preclinical the MTAP-deleted immunohistochemistry tumor sufficient on controls. XX by derived the validated slide, XXX% tumor in complete of lung of patient cancer tumor extinguished demonstrating we on In by patient model SDMA of same Slide vehicle MTAP-deleted reduction see left, methionine is xenograft we MTAP with deleted models inhibition dependent across to block anti-SDMA deleted of antibody. SDMA So of IDEXXX evaluated inhibition can to subset PRMTX growth and you XX% reduction dose you tumors models, measure tumor In and in right, That on in activity our at in tumor milligrams by XX compared as tumor the SDMA MTAP please to preclinical an per the a SDMA Nine dose models vivo. SDMA shown time X,
lung one XX. slide X, of reduced is deleted you achieve the right, patient in shown indicating from indications model, XX% vignettes of our cell in of couple SDMA this study. cancer extensive high program H-score tumor. IDEXXX give XX. On tumor by XXX% tumor a the the the slides. production population next cell standing of the with by squamous slide interest non-small as The zero interest lung of PDX will key growth inhibition carcinoma on the and With two showed We we SDMA was on for MTAP vehicle panel SDMA the PD, the suppression arm On IDEXXX middle in to to an respect H-score treatment, of of
baseline regression another quite is indication, example saw in that IDEXXX and as can tumor XX. study. an in the had in Here tumors, the XXX, control we panel. On you tumor disease the by on This of end right. SDMA where animals H-score signal is same of is middle see slide gone you XX% max can of see as residual XXX the far treated high a
earlier I As across observed study, as X Phase biomarker to SDMA plasma Cohorts biomarker. on as reduction PD escalation following the SAM through X mentioned PD Cohort plasma date. We've we're clinical the X treatment and a tumor SAM significant in tissue peripheral dose
post can you among reduction on example, recently consistent with SAM Cohort mean X weeks after treatment clear As see of three the patients the our evaluable a plasma of deep and therapy. in left an reduction XX%
date, see the you all SAM that right, increasing exposure, can trial inhibition exposure with percent the drug to evaluable exposure-dependent patients modulation. across indicating is On plasma dependent associated on
slide, next from trial. we'll the the tumor to the On PD move
in associated reduction Slide So very exposure here to we XX, on target tumor see pleased types. were tumor SDMA
SDMA X brown of first treatment the are and nuclear positive SDMA from the indicating Cohort patient dark by little pancreas panel shown Cohort cytoplasmic panel is with a Notably, patient's pre-dose top absent is also biopsy middle SDMA AUC surrounded patient the in pancreas in paired emerging staining X, detectable and staining on although staining lighter SDMA This biopsies from which shown IDEXXX modest plasma drug X.X-fold than response to in on pre-dose in a far in ovals showed cancer the both pancreas biopsy. Those treatment. cytoplasmic Our tumor about in cancer panel. tumor the and the X. on modulation Cohort the detectable, cancer nuclear staining, higher pharmacological nuclei Brown middle left patient an came displayed cytoplasmic treatment exposure are and reduction SDMA tumor. pretreatment bottom
for on exposure for the were vast slide of of SDMA CDX PDX slide. slide. shown pre-dose on control see in lung see SDMA of intensity, strong well I'll higher as next as patient preclinically, graph at of patient up exposure patient XX the in almost staining completely receiving at cells plasma Finally, regressions only we the you The the MTAP-deleted complete zero. Cohort on and on The majority treatment pre-dose and reduction sum this high right, maximum tumor as the post growth right. in in models of milligrams we the The plotted Cohort can significant from the the for plasma on saw scores was higher the that Phase by cohort We've maximally steady tumor SAM plotted contrast, drug X Clinical and lab SDMA in the on go in CohortX in above within had predicted benchmarked the cells on a the was Clinically, In receiving studies, details a across biopsy what almost next milligrams graph IDEXXX in tumor score response this cancer we the SAM right, HXXX, cohort an We'll exposures cohort negative bar was sample the tumor relationship is reduction and biopsy side the the milligrams patients first, treatment majority X the also reduction exposures dependent scores the the the steady tumor loss kilogram panel cancer SDMA observations. end XX%. discussed detectable those model these in oral are X deletion X. X-fold X Slide more on kilogram. IDEXXX biopsy dose using model. the XX% exposure lung patient. vast once tumor the kilogram SDMA per on XX lung XX Based in state preclinical bar of efficacy efficacy noting tumor in exposures, and and is shown patients showing against in range than This concentration right are cohort in X. at MTAP tumor is from XXX, [indiscernible] presentation for reduction XX% daily with XX observations, XX doses per We've the right, currently this a for is based exposures standing tumor the representative the cohort dive or the this using plasma preclinical through is X on biopsy the in the on exploring it's cancer in worth plus. IDEXXX efficacious MTAP per central higher getting on target the of in X. X exposure SDMA for vivo suppressed X deeper of SDMA in is pathologist state high range achieved X. multiple observed for in
I'll So the to Yujiro. with hand presentation back that
