To­ward the end of sum­mer, Mass­a­chu­setts-based Cin­Cor Phar­ma was rid­ing high with a $225 mil­lion raise, tout­ing a pos­i­tive da­ta read­out. But a clos­er look un­der the hood has re­vealed a few hic­cups in its Phase II.

Ma­son Free­man

Cin­Cor on Mon­day un­veiled topline re­sults from its Phase II tri­al, dubbed HA­LO, eval­u­at­ing bax­dro­stat in pa­tients with un­con­trolled hy­per­ten­sion who are tak­ing up to two blood pres­sure med­ica­tions. The tri­al whiffed on its pri­ma­ry end­point of eval­u­at­ing change from the “base­line in mean seat­ed” sys­tolic blood pres­sure (SBP) in the in­tent-to-treat pop­u­la­tion in all dosage lev­els.

Cin­Cor did try to sal­vage things by tout­ing the safe­ty of the can­di­date along with an analy­sis of non-His­pan­ic pa­tients, which amount­ed to around 47% of the tri­al par­tic­i­pants. Here, the biotech said around 81%-89% of the group had a re­duc­tion in SBP of 12.6 mmg, earn­ing a p-val­ue of p=0.001 in the high dose of 2 mg.

Cin­Cor CMO Ma­son Free­man said in a state­ment:

While we still need to learn more about the fac­tors dri­ving dif­fer­ent re­spons­es in our pre-spec­i­fied sub-group analy­ses, it is clear that bax­dro­stat gen­er­at­ed dou­ble-dig­it SBP re­duc­tions in study sub-groups, which in­clude Black/African Amer­i­can pa­tients, rep­re­sen­ta­tive of ap­prox­i­mate­ly 81-89% of the hy­per­ten­sive pop­u­la­tion of the US. The da­ta al­so demon­strate a fa­vor­able safe­ty pro­file and tol­er­a­bil­i­ty across the treat­ed pa­tient groups. Pa­tients in HA­LO were not pre-se­lect­ed for in­clu­sion based on al­dos­terone, renin, or oth­er hor­mon­al char­ac­ter­is­tics, sug­gest­ing bax­dro­stat’s util­i­ty in the un­con­trolled hy­per­ten­sive pop­u­la­tion may be broad­er than ex­pect­ed.

Cin­Cor is not look­ing to stop its work on bax­dro­stat, ex­pect­ing the Phase III tri­als to still oc­cur with­in the first half of next year. The pro­gram re­mains “on track” for a po­ten­tial NDA sub­mis­sion in 2025. Cin­Cor’s stock price $CINC has dropped around 43% since open­ing from around $26 a share down to un­der $15.

At least one an­a­lyst was left search­ing for an­swers from the da­ta. Ever­core’s Umer Raf­fat wrote to in­vestors that “over­all, this tri­al is im­pos­si­ble to in­ter­pret…not just the pri­ma­ry da­ta, but al­so non-His­pan­ics [da­ta].” He added there was a “re­al­ly quite pro­found” place­bo re­sponse that may have af­fect­ed things.

“If we all agree that there is an odd pbo re­sponse in this tri­al, then we can al­so not trust the very ba­sis of Cin­cor’s as­ser­tion that non-his­pan­ics looked good,” Raf­fat wrote. “Said dif­fer­ent­ly, if there are re­al tri­al con­duct is­sues which makes it hard to in­ter­pret the tri­al, that same ra­tio­nale ap­plies to the 2 mg arm in non-his­pan­ic sub­group as well.”

But while the biotech is fac­ing a dip, some an­a­lysts are not throw­ing in the tow­el just yet. An analy­sis from Den­nis Ding at Jef­feries stat­ed that while the HA­LO tri­al was missed and was not ex­pect­ed by Wall Street, the tri­als were not a core piece of the the­sis.

“This could be per­ceived as a clear­ing event since in­vestors were so ner­vous head­ing in­to HA­LO, and with the topline now be­hind us, in­vestors could fo­cus more on the path ahead in­clud­ing Phase III start­ing by mid-2023. Fur­ther, de­spite the neg­a­tive topline, we’d ar­gue the un­con­trolled pop­u­la­tion was nev­er go­ing to be ef­fi­cient­ly com­mer­cial­ized any­way nor core to the the­sis and the block­buster op­por­tu­ni­ty may still be in­tact in treat­ment-re­sis­tant pa­tients,” Ding said.

Ding added that Cin­Cor will meet with the FDA to dis­cuss the up­com­ing Phase III, sur­mis­ing that the biotech will run two sep­a­rate Phase III tri­als and that it will be more “cau­tious and vig­i­lant” on the de­sign of the tri­al and may have more mon­i­tor­ing to re­duce the ef­fect of the place­bo.

Cin­Cor has got­ten a lot of at­ten­tion and funds over bax­dro­stat. In Au­gust, it gar­nered $225 mil­lion af­ter tout­ing ini­tial Phase II da­ta. And last year, the com­pa­ny scored a $143 mil­lion Se­ries B round led by Gen­er­al At­lantic with a $100 mil­lion Nas­daq fil­ing launch­ing on­ly a few weeks lat­er.

Cin­Cor’s Phase II al­so comes as it is fac­ing stiff com­pe­ti­tion from oth­er biotechs look­ing to get a hy­per­ten­sion drug in­to the mar­ket. Philadel­phia-based Min­eralys re­cent­ly un­veiled Phase II da­ta for its al­dos­terone syn­thase in­hibitor for treat­ing hy­per­ten­sion and its as­so­ci­at­ed car­dio­vas­cu­lar dis­eases, which did reach its pri­ma­ry end­point.

DC District Court Judge Christopher Cooper today granted Vanda Pharma’s request to require the FDA to disclose more info on the complete response letter for its sleep disorder drug Hetlioz.

The melatonin receptor agonist is approved by the FDA to treat non-24-hour sleep-wake disorder, a circadian rhythm disorder. But in 2018 Vanda filed a supplemental application to market Hetlioz as a treatment for jet lag, which the FDA rejected in August 2019, with few details on what Vanda needed to correct course, according to the company.

Paul McKenzie took over as CEO of Australian pharma giant CSL this month, following in the footsteps of long-time CSL vet Paul Perreault.

With an eye on mRNA, and quickly commercializing its new, $3.5 million-per-shot gene therapy for hemophilia B, McKenzie and chief medical officer Bill Mezzanotte answered some questions from Endpoints News this afternoon about where McKenzie is going to take the company and what advances may be coming to market from CSL’s pipeline. Below is a lightly edited transcript.