Marc de Garidel, CinCor Pharma CEO (Eric Piermont/AFP via Getty Images)

Cin­Cor’s hy­per­ten­sion can­di­date flops a PhII test but plans to charge ahead with piv­otal study

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.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

Jeff Bluestone (R), Sonoma Biotherapeutics CEO

Jef­frey Blue­stone brings his start­up haul to $400M+, join­ing forces with Re­gen­eron on cell ther­a­pies

These days, when Jeffrey Bluestone gets together with his contemporaries in science, the conversation often turns to retirement plans.

But a little more than three years ago, Bluestone reached a momentous turning point in his career, exiting a prestigious post at UCSF, where he had spent decades in the scientific pursuit of new therapies. And it had nothing to do with retirement anytime in the near future.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

J&J bows out of RSV vac­cine race, end­ing PhI­II study and ced­ing to Pfiz­er, GSK

Johnson & Johnson announced Wednesday morning it is ending development of its adult RSV vaccine that was in the middle of a 27,200-patient trial, giving up a big slice of what’s expected to be the next multibillion-dollar pharma market.

The decision came down to the shifting RSV “competitive landscape,” a company spokesperson tells Endpoints News, adding the “breadth of options” was much different than when J&J first started its pivotal study. The spokesperson declined to comment on the Phase III data, saying only the shot is undergoing an “ongoing assessment.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

No longer ‘dead or just hi­ber­nat­ing,’ drug­mak­ers re­turn to heart med­i­cines

In 2015, now-FDA Commissioner Robert Califf joined industry, academic and regulatory representatives in Washington to discuss why more drugs weren’t in development for cardiovascular diseases, the leading US cause of death and once a mainstay of pharmaceutical industry blockbusters.

The group pointed to many reasons. Clinical trials could take years and testing was expensive. Wide availability of generic drugs made the commercial prospects uncertain. Their paper title summed up the mood: “Cardiovascular Drug Development: Is it Dead or Just Hibernating?”

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Van­da wins court case against FDA over dis­clo­sure of CRL de­tails for sleep drug

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.

Gun­ning for 2023 ap­proval, GSK de­tails PhI­II da­ta for Jem­per­li in front­line en­dome­tri­al can­cer

GSK has a new slate of data to offer on its PD-1 inhibitor, Jemperli — data that the pharma giant hopes will cement one of the four drug approvals it’s expecting this year.

While Jemperli (dostarlimab) is already approved for a subset of patients with second-line endometrial cancer, GSK set out in the Phase III RUBY trial to test it as an earlier line of treatment while also enrolling a broader group of patients. In an interim analysis, Jemperli was shown to extend progression-free survival for both the subset and the overall trial population when added to chemotherapy.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

CSL CEO Paul McKenzie (L) and CMO Bill Mezzanotte

Q&A: New­ly-mint­ed CSL chief ex­ec­u­tive Paul McKen­zie and chief med­ical of­fi­cer Bill Mez­zan­otte

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.