Ax­o­vant races to PhI­II de­men­tia study as nelotanserin clears an ear­ly hur­dle, but ques­tions linger

Vivek Ra­maswamy

Ax­o­vant says that its drug nelotanserin has cleared an ear­ly hur­dle in a Phase II study for Lewy body de­men­tia, trig­ger­ing a de­ci­sion to ex­pand the mid-stage tri­al and hit­ting the green light for a Phase III to get start­ed lat­er this year. But in­vestors are like­ly to ques­tion a stum­ble on key sec­ondary goals.

A snap­shot of re­sults for the first tiny group of 11 pa­tients con­clud­ed that they were demon­strat­ing sta­tis­ti­cal­ly sig­nif­i­cant re­spons­es to the drug on the pri­ma­ry end­point. These pa­tients in­clud­ed peo­ple suf­fer­ing from Parkin­son’s as well as Lewy body de­men­tia. They were re­cruit­ed af­ter suf­fer­ing from fre­quent vi­su­al hal­lu­ci­na­tions.

“The pri­ma­ry out­come mea­sures of the study were ex­trapyra­mi­dal signs as as­sessed by Uni­fied Parkin­son’s Dis­ease Rat­ing Scale (UP­DRS) Parts II + III and safe­ty,” the com­pa­ny re­port­ed.

There was a big hitch, though. The tri­al did not hit sec­ondary end­points laid out by in­ves­ti­ga­tors to track the fre­quen­cy of vi­su­al hal­lu­ci­na­tions, in­clud­ing both a stan­dard SAPS as­sess­ment as well as an end­point they cre­at­ed in­ter­nal­ly at Ax­o­vant. And that may have weighed in on in­vestors’ re­sponse to the re­sults, with Ax­o­vant’s stock up on­ly 5% in pre-mar­ket trad­ing.

Ax­o­vant, the first of Vivek Ra­maswamy’s biotechs to get start­ed, plans to hus­tle in­to the ex­pand­ed Phase II for the drug — a 5HT2A an­tag­o­nist — as it wastes no time in get­ting the Phase III up and run­ning. Ra­maswamy has made no se­cret of his plans to ac­cel­er­ate R&D at his com­pa­nies. And Ax­o­vant is the most ad­vanced with a big tri­al un­der­way for Alzheimer’s.

Ax­o­vant al­ready faces an es­tab­lished mar­ket play­er. Aca­dia’s ri­val drug Nu­plazid won FDA ap­proval for Parkin­son’s de­men­tia last spring, but on­ly af­ter reg­u­la­tors ex­pressed their safe­ty con­cerns, not­ing a dis­tinct in­crease in the num­ber of deaths as well as the rate of ad­verse events among the pa­tients tak­ing the drug com­pared to the con­trol arm of the study — even if there was no ob­vi­ous clue what was trig­ger­ing those events.

Ax­o­vant’s hope is that it can come out of clin­i­cal tri­als with a bet­ter suc­cess rate and a clean­er safe­ty pro­file as both com­pa­nies tar­get a broad pa­tient pop­u­la­tion suf­fer­ing from dif­fer­ent forms of de­men­tia.

“I am in­trigued by the ben­e­fits ob­served on the UP­DRS in this study,” stat­ed Dr. James Lev­erenz, Chair, Sci­en­tif­ic Ad­vi­so­ry Coun­cil of the Lewy Body De­men­tia As­so­ci­a­tion and Di­rec­tor of the Cleve­land Lou Ru­vo Cen­ter for Brain Health at the Cleve­land Clin­ic. “If a sin­gle drug could si­mul­ta­ne­ous­ly ad­dress the mo­tor and neu­ropsy­chi­atric symp­toms of Lewy body de­men­tia, which the pub­lished lit­er­a­ture sug­gests may be the case for 5HT2A an­tag­o­nists, it would rep­re­sent a unique and im­por­tant ad­vance for the treat­ment of this con­di­tion. I look for­ward to re­view­ing the full dataset lat­er this year.”

Tal Zaks, Moderna CMO (Moderna via YouTube)

UP­DAT­ED: NI­AID and Mod­er­na spell out a 'ro­bust' im­mune re­sponse in PhI coro­n­avirus vac­cine test — but big ques­tions re­main to be an­swered

The NIAID and Moderna have spelled out positive Phase I safety and efficacy data for their Covid-19 vaccine mRNA-1273 — highlighting the first full, clear sketch of evidence that back-to-back jabs at the dose selected for Phase III routinely produced a swarm of antibodies to the virus that exceeded levels seen in convalescent patients — typically in multiples indicating a protective response.

Moderna execs say plainly that this first stage of research produced exactly the kind of efficacy they hoped to see in humans, with a manageable safety profile.

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Trans­port Sim­u­la­tion Test­ing for Your Ther­a­py is the Best Way to As­sure FDA Ex­pe­dit­ed Pro­gram Ap­proval

Modality Solutions is an ISO:9001-registered biopharmaceutical cold chain engineering firm with unique transport simulation capabilities that support accelerated regulatory approval for biologics and advanced therapeutic medicinal products (ATMP). Our expertise combines traditional validation engineering approaches with regulatory knowledge into a methodology tailored for the life sciences industry. We provide insight and execution for the challenges faced in your cold chain logistics network.

Tillman Gerngross, Adagio Therapeutics CEO

An­ti­body leg­end Till­man Gern­gross is el­bow­ing his way in­to the Covid-19 R&D cru­sade: 'I don’t see this end­ing any­time soon'

One of the most influential — and outspoken — scientists at work in the field of antibody discovery is jumping into the frenzied race to create new therapeutics to treat and prevent Covid-19. And he’s operating with the conviction that the current outbreak now once again spreading like wildfire will create plenty of demand for what he has in mind.

Dartmouth professor and Adimab CEO Tillman Gerngross tells me he’s raised $50 million from a group of close VCs to spin out a new company — Adagio Therapeutics — with a full C-suite team assembled to hire up a staff and keep rolling toward the clinic.

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Full Bril­in­ta study re­sults show the blood thin­ner re­duces rate of sec­ondary stroke

AstraZeneca once projected its Brilinta drug to peak at $3.5 billion in sales, and though the blood thinner never reached that lofty goal, it received the latest positive signs in a string of recent good news.

The pharma released full details from its THALES study Thursday morning, which measured the effects of Brilinta and aspirin against aspirin alone in treating patients who had an acute ischemic stroke or transient ischemic attack. When taken twice daily with once-a-day aspirin for 30 days, the Brilinta combo reduced the risk of stroke and death by 17 percent, meeting the primary endpoint of the study.

Norbert Bischofberger, Kronos CEO

Gilead­'s ex-R&D chief Bischof­berg­er heads back to the biotech gi­ant to pick up a pair of late-stage drugs that had been put aside

Norbert Bischofberger knows entospletinib well.

Back during his long, blockbuster run as head of R&D at Gilead, researchers had once held some high hopes for this drug. But to make it work, he and the team felt it would need a new companion diagnostic to identify patients. There was talk of a combo approach to give it more punch. But the market was small, making them wonder if it would be worth going through a lengthy development cycle to get it through a pivotal.

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The $1B Mer­ck-Bay­er drug that di­vid­ed car­di­ol­o­gists in March gets pri­or­i­ty re­view

Three months after Merck published in the New England Journal of Medicine data that left doctors and investors divided over just how well its experimental heart drug worked, the FDA has handed that drug priority review. A decision is now due by January 20, 2021.

Merck first announced the drug, known as vericiguat, as a Phase III success last November. In 2016, Merck had paid $1 billion upfront for US rights to the Bayer-developed drug. Early projections foresaw a few hundred million a year in sales, but the unspecified late-stage success raised the possibility for far more. After all, Novartis’s flagship heart drug, Entresto, was earning $1.7 billion per year and was expected to reach up to $4 billion in annual sales.

GSK’s Shin­grix leader Guil­laume Pfe­fer has jumped on board Flag­ship to helm a biotech hy­brid as Afeyan’s lat­est CEO-part­ner

After spending 4 years in a senior post with GlaxoSmithKline’s star team positioning Shingrix for a blockbuster approval, Guillaume Pfefer is headed back to the biotech world — in style.

Pfefer has signed on to join Noubar Afeyan’s busy group of partners at Flagship, and he’s taking the helm of an upstart — which today is being merged with another Flagship startup — with some grand plans of its own. The announcement this morning notes that Pfefer will run Kintai Therapeutics, one of the grads of the Flagship labs.

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Who are the women blaz­ing trails in bio­phar­ma R&D and lead­ing the fight against Covid-19? Nom­i­nate them for End­points' spe­cial re­port

One of the many inequalities the pandemic has laid bare is the gender imbalance in biomedical research. A paper examining Covid-19 research authorship wondered out loud: Where are the women?

It’s a question that echoes beyond our current times. In the biopharma world, not only are women under-represented in R&D roles (particularly at higher levels), their achievements and talents could also be undermined by stereotypes and norms of leadership styles. The problem is even more dire for women of color.

Mer­ck KGaA takes its I/O op­tion on F-star Ther­a­peu­tics; Nephron spends $215M, eye­ing spot in Covid-19 vac­cine chain

→Merck KGaA has taken an early option on an immuno-oncology program developed at F-star Therapeutics. This is their second option in the collaboration. And they added a pair of preclinical discovery programs to the alliance as well.

Any biotech going public these days wouldn’t feel right if they didn’t upsize the offering. And that’s just what Phase I biotech Pandion Therapeutics did. The autoimmune company is now selling 7 million shares, a 1.5 million share bump, for $16 to $18 a share.