you, Thank Jacob.
to Turning conducting X, a resistance. as two we to GR mechanism each distinct clinical ORIC-XXX, a have of trials Slide been of examining inhibition of action cancer means reverse
metastatic study a patients in cancer. ORIC-XXX with The of is prostate with enzalutamide first combination
metastatic chose specifically, of of with enzalutamide receptor clinical modulator, are since progression, action. ORIC-XXX a we most inhibition reversal possible, enzalutamide of simultaneous any on bypass resistance as pathway, a Given in novel could was treatment that as time so or the of paradigm who have we of cancer hypothesis test to progressing post expected as patients different agent approaches enzalutamide. ORIC-XXX for not population signal androgen entirely that mechanisms single identify efficiently the namely, to was GR switching a to single this adding at the a prostate enzalutamide activity, patient to setting our arm involve potential objective second-line By
The of biopsies, component translational once combination sampling extensive of on-study pharmacodynamics two dose milligrams RPXD for reported of trying on This one, tumor ORIC-XXX and which The part on the label enzalutamide. the our on We the study part were with and blood portion also multicenter the two shutdown trial. were that interim of was sampling target. dose trial primary was tumor parts. pharmacokinetics, a baseline that relied the an which as RPXD, we and that GR downstream target the of control to to through or were we study. identified the exposures plan achieving open rate expansion dose included recommended to patients. longitudinally GR RPXD, And of of genes. endpoint. targets disease with enzalutamide measurement of progression ORIC-XXX profiling weeks, baseline of through after Here, we Phase After achieving escalation into trial, enrolled was demonstrated endpoint to effort XX previously signaling determination of important was survival work able efficacy were extend at we at the dose to the and pharmacodynamic that dose This heavily Pharmacokinetic secondary itself. establishing X an were XX portion the inhibit with we in genomic daily, free sufficient studies, serial patients ORIC-XXX at be standard we the XXX confirm performed in analysis through integral
well we whose excludes through was potentially resistance. of of of variants, be were in active consideration namely the such patient which had at a resistance, target variants or Another to cancer GR we important population resistance mechanisms able plasticity, of tumors for that to the baseline, patient expect mechanism of of a enzalutamide one identify would profiling that that the androgen the patients described mutations This primary binding harbor become receptor, AR-independent. population implying markers lineage ORIC-XXX point alternate inhibit and tumors as splice
shifted addition, patients target previously focus to on outcome on one enrolling ORIC-XXX. our which analysis we referenced with in endpoint regulatory XX In well agents patients free progression glucocorticoid up, as as to and for followed for the measure of was patients would has per expansion survival After such weeks disease rate. the with in follow the we into RPXD an time although are Whereas atezolizumab. whose such cabazitaxel at now free also that small ample as order precedent. treatment which on the in high is new – efficacy, the cabozantinib identify patients XX plus additional were progression dose agents to focused the tumors efficacy in used numbers, docetaxel, secondary enrolled setting, which had arm the we benchmarks perform enzalutamide of combinations as least them as of are And primary and we and control a the as we was the development, and expresses single XX of which survival, this receptor, of study, protocol, part the post
Turning X, this me to of the summarize Slide analysis. let results
of Phase dose. at safety, regimen was the the tolerated First, well combination in generally recommended X terms
levels we were the target for which achieving target ORIC-XXX genes. able work target Next GR with GR drug extensive regulation PK/PD engagement, we and measuring respect by confirm demonstrated exposure of to sufficient to down that were coverage,
were progression was approved PFS the different not population. context patient at the the modulator, demonstrate insufficient evidence high we in DCR patients ORIC-XXX with PFS of no Finally, after with to median GR endpoints. In Nevertheless, lineage Of therapies expressed ORIC-XXX the with And based control despite upon continued on the clinical on study AR AR data able of any enzalutamide the disease as exposures baseline, XX.X%. the in of achieving or majority endpoint new at alternate the of note, patient values were and resistance sufficient same evidence X.X the support tumor efficacy moderate recorded patients to levels Gr. population to months. with consistent outcome development, tumors high currently regimens for was of population seen identified efficacy not these in from of to and target therapies of through In the and the development. patient in of unselected of particular, in that were the biological biopsies plasticity efficacy primary as benefit we moderate expression, weeks alterations XX an our well of patient meaningfully rate activity,
weeks expansion at we dose we in XX extensive inhibit study, multicenter labeled nab-paclitaxel, dose shutdown. open the RPXD, pancreatic which of RPXD, patients. fourth in us per we $XXX of primary in again nab-paclitaxel identify was in clinical in patients And was as exposures and The sampling eligible were to the combination factor second study free identified label an And signal to lower than weekly this triple cohort GR the escalation including was After reported the in that therapy, defined target milligrams one, negative the ORIC-XXX three sufficient adenocarcinoma, cycle. survival an X, parts. as of squared without that the also a portion the establishing line secondary through patients with of we pharmacokinetic the ORIC-XXX Slide nab-paclitaxel growth This were was cohort dose ductal rate, although component, with with with trial, combination enzalutamide late breast support with and with of progression advanced the the two to sufficient Turning a efficiently for pharmacodynamic interest, as other the important resulted as multi on tumor indicated patients of dose of target We ORIC-XXX frontline of population ovarian tumors. milligrams part testing achieving on trial in study, two In target trial ORIC-XXX these previously cohorts three for to RPXD opened which meter to portion be the cancer, demonstrated the achieving performed enrolled four-week rates neutropenia dose, genes, translational we solid arm the and which with had with we studied setting that put of patient in had a position types. that endpoint part response of to cancer. possible. best endpoint. The objective single nab-paclitaxel for
expansion taxane-based have a on we the Specifically, dose progressed treated patients previously to required been therapy. in with and
While bar, this activity. an felt this distinguish we way a from could only pure that effect taxane-driven ORIC-XXX higher in clinical we is
ovarian modest. While retreatment in effect there and is is cancer generally a this TNBC, effect taxane,
for And of study for so benchmark we ovarian in cancer. set six our months PFS a
effect hand in literature. the relapsed reported no On taxane retreatment there in the other is measurable PDAC,
four to order looking cohorts ORIC-XXX of total three After weeks and a or we enrolled were a the cohort. at to one, for and part perform them longer we least RPXD so PFS XX identify And dose in primary analysis. patients with patients XX this enrolling the nab-paclitaxel in achieve the in expansion efficacy months across follow to of XX
well target combination generally coverage Turning XX, And at X engagement. recommended Phase and tolerated dose. the of PD safety data good as demonstrated I to showed evidence this the Slide profile PK regimen of target stated, data was
PDAC was tumor so across the showed high status particularly was types pre tested most levels GR high most population. identify In of in but patient tumors tumor ovarian interest, across addition, types, expression necessary tumor GR cancer, target and in of that two biopsy patients a expression these types not to two patient subset of selection of baseline by
in high the biological demonstrated confirmed activity cohort, conclude one the only cohort. development we addition levels of in Furthermore, cancer target we X.X patients free to we no chemotherapy. with were PDAC the was evidence that we taxane pretreated, of in expansion progression median glucocorticoid in and that see these response cohorts In taxane saw survivals clinical and ovarian to partial responses Although data objective PDAC months these. of and regimen. X.X at continued in nab-paclitaxel are months the cancer these evidence this these to ORIC-XXX ovarian of resistance Therefore, receptor, did and who resensitize there patients sufficient these from activity not tumors support retreatment insufficient the reverse
Now, interpret what on these review here and turning offer the I’d we’ve may to presented us Slide learned we why to how today, trials our XX, and two have sufficient seen like clinical help that benefit. data opinion might consider clinical not clinical from
with receptor First, receptor as learned both glucocorticoid inhibitor combined we cytotoxic chemotherapy, well that an be as a androgen modulator. could safely
over GR inhibit longitudinally shutdown clinical course target patients Second, ORIC-XXX glucocorticoid we of combinations, the the measure to effect target exposures could of learned capable was that in patient We treatment. achieving and cover these receptor. samples in and of sufficient this
answer cells hitting down of then profiling tumor In the we of in relevance performed as we the may By pathway. of target, resistance resistance heterogeneity, upon single tumor and but may cells as an may suggested work see resistance between and other did also in a that same ORIC-XXX clinical heterogeneity differences lie not while with within lesions the genomic if some relying two affecting benefit. be lesions could be patient. I studies, We clinical the separate in non-GR absence GR similar tumor From in and/or tumor a difference present why the as cells resistance part between were cells, mean other as expect shutting mechanism. effect. not GR resulting translational a So tumor we both redundancy upon GR mechanisms. pathway, would tumor, tumors alternate A within relying indeed that the mechanism, a measurable tumor be of affect only single a would
may drive for more be may pathway a resistance then is possible tumor is progression Such pathways In finally, in a these And key the in tumor be seen a two lack possible dependency pathways a in coexisting to be to setting, complexity tumor resistance such trials. explanation itself or GR when GR addition, the clinical may GR of within addition clinical it’s In benefit cell. not redundant one patients. that sufficient inhibited.
observations setting. so the And in clinical transfer don’t to patients in made lab a
didn’t target drug benefit not uncommon biology, We’re always further meet obviously that bar disappointed for clinical novel trials clinical studying the development. our two results which when Negative these trials especially are the translate and doesn’t oncology clinic. development, from in into
quickly us For that reason, we get answer designed these studies with clearly defined as patient to populations to as to possible. as efficiently enable and an
were I think the sufficient data to tough, ORIC-XXX enable delivered The decision but we right make they achieved us discontinue to the to that. and studies well run, program.
the participating details participated in study like families. these clinical to We ORIC-XXX me all In patients Jacob. the would let back expect who hand it that, trials our more I on studies future study to in team, share the all and thank to of and the staff at With the and publications. clinical most investigators conclusion, their sites, support