Aptinyx shares crater as lead drug fails in PhII neu­ro­path­ic pain study

Aptinyx’s ap­proach to mod­u­lat­ing the NM­DA re­cep­tor to treat dis­or­ders of the cen­tral ner­vous sys­tem has hit a sig­nif­i­cant snag, as its lead ex­per­i­men­tal drug failed a mid-stage study in pa­tients with di­a­bet­ic pe­riph­er­al neu­ropa­thy (DPN), oblit­er­at­ing the re­cent­ly pub­lic com­pa­ny’s stock on Wednes­day.

Nor­bert Riedel

The drug — dubbed NYX-2925 — was de­vel­oped by the Evanston, IL-based biotech that went pub­lic last Ju­ly bank­ing on its ap­proach to mod­u­late NM­DA re­cep­tors, which are cru­cial to brain and ner­vous sys­tem func­tion. The Phase II tri­al pit­ted three oral dos­es of the drug (10 mg, 50 mg, or 200 mg) ver­sus a place­bo in 300 pa­tients over four weeks. The ex­per­i­men­tal treat­ment failed to con­fer a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in av­er­age dai­ly pain — as mea­sured by a Nu­mer­i­cal Rat­ing Scale (NRS) — at week four, miss­ing the pri­ma­ry end­point of the study.

The com­pa­ny’s shares $AP­TX plum­met­ed about 70% in ear­ly trad­ing.

The com­pa­ny sug­gest­ed its 50mg dose had the most promis­ing im­pact. Pa­tients treat­ed with the dose showed a 1.61-point re­duc­tion in av­er­age dai­ly pain on the NRS — the largest de­crease among the dose lev­els eval­u­at­ed — ver­sus the 1.23-point fall in those giv­en the place­bo, re­sult­ing in a non-sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment (p=0.1586).  Pa­tients on the 50 mg dose al­so showed im­prove­ment on key sec­ondary end­points, in­clud­ing sleep and pain on walk­ing, Aptinyx added.

“While the study did not meet its pri­ma­ry end­point…we be­lieve the to­tal body of clin­i­cal da­ta in­di­cates the po­ten­tial of NYX-2925 to treat chron­ic pain,” Aptinyx chief Nor­bert Riedel said in a state­ment, adding that the com­pa­ny is now in process of find­ing a way for­ward for NYX-2925.

“It seems that at best that path for­ward may con­sist of an­oth­er phase II tri­al in DPN, us­ing the two dos­es that showed a nu­mer­i­cal dif­fer­ence to place­bo (50mg and 200mg) and in­cor­po­rat­ing longer du­ra­tion of treat­ment (8 or 12 weeks). Such a study could be­gin in H2 2019 and pro­duce a re­sult in 2020. How­ev­er, it is not clear yet whether the com­pa­ny’s board, in­ves­ti­ga­tors, ad­vi­sors and in­vestors will en­dorse the in­vest­ment in that (cost­ly) tri­al. In­vestors are like­ly to elim­i­nate all val­ue for this pro­gram from the com­pa­ny’s stock to­day and thus leave the stock re­liant up­on ear­li­er pro­grams tar­get­ing more chal­leng­ing dis­ease in­di­ca­tions in­clud­ing cog­ni­tive im­pair­ment in Parkin­son’s dis­ease (NYX-458) and post-trau­mat­ic stress dis­or­der (PTSD) (NYX-783),” Leerink’s Ge­of­frey Porges wrote in a note.

In a sep­a­rate on­go­ing ex­plorato­ry mid-stage study, NYX-2925 has shown en­cour­ag­ing re­sults in a small group of pa­tients with fi­bromyal­gia, the com­pa­ny not­ed in an in­ter­im analy­sis post­ed last month. The full re­sults of that study are ex­pect­ed in the first half of this year.

“We don’t re­gard the stock as “dead mon­ey” af­ter to­day’s news, but do rec­og­nize that a sig­nif­i­cant part of its pri­or val­u­a­tion is now im­paired. Ear­li­er this month the com­pa­ny pro­vid­ed pos­i­tive bio­mark­er da­ta for NYX-2925 in its oth­er in­di­ca­tion of fi­bromyal­gia; at this stage those bio­mark­er ef­fects are en­cour­ag­ing but in­suf­fi­cient,” Porges added.

Var­i­ous drug de­vel­op­ers are fo­cus­ing on the NM­DA re­cep­tor, de­vel­op­ing com­pounds to ac­ti­vate or in­hib­it it to treat CNS dis­or­ders, but that strat­e­gy has seen a se­ries of set­backs in part due to safe­ty con­cerns. Aptinyx be­lieves its ap­proach — with­out ever ful­ly turn­ing the re­cep­tor “on” or “off” — will al­low it to evade these chal­lenges. Al­ler­gan has bought in­to this Aptinyx phi­los­o­phy, hav­ing li­censed their de­pres­sion drug, which is now called AGN-241751. Aptinyx it­self was was spun out of Al­ler­gan’s $1.7 bil­lion buy­out of Nau­rex which CEO Brent Saun­ders want­ed for its lead NM­DA drug — now dubbed ra­pastinel — for ma­jor de­pres­sion.

In terms of pain, pa­tients have few ef­fec­tive op­tions oth­er than high­ly ad­dic­tive opi­oids, and there­fore drug de­vel­op­ers work­ing on non-opi­oid op­tions are keen­ly watched. This is like­ly one of the rea­sons the FDA grant­ed NYX-2925 fast track sta­tus for neu­ro­path­ic pain as­so­ci­at­ed with DPN.

UP­DAT­ED: Bio­gen shares spike as ex­ecs com­plete a de­layed pitch for their con­tro­ver­sial Alzheimer's drug — the next move be­longs to the FDA

Biogen is stepping out onto the high wire today, reporting that the team working on the controversial Alzheimer’s drug aducanumab has now completed their submission to the FDA. And they want the agency to bless it with a priority review that would cut the agency’s decision-making time to a mere 6 months.

The news drove a 10% spike in Biogen’s stock $BIIB ahead of the bell.

Part of that spike can be attributed to a relief rally. Biogen execs rattled backers and a host of analysts earlier in the year when they unexpectedly delayed their filing to the third quarter. That delay provoked all manner of speculation after CEO Michel Vounatsos and R&D chief Al Sandrock failed to persuade influential observers that the pandemic and other factors had slowed the timeline for filing. Actually making the pitch at least satisfies skeptics that the FDA was not likely pushing back as Biogen was pushing in. From the start, Biogen execs claimed that they were doing everything in cooperation with the FDA, saying that regulators had signaled their interest in reviewing the submission.

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Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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Atul Deshpande, Harbour BioMed chief strategy officer & head, US operations (Harbour BioMedO

An­oth­er biotech IPO set-up? Multi­na­tion­al biotech leaps from round to round, scoop­ing up cash at a blis­ter­ing pace

A short four months after announcing a $75 million haul in Series B+ fundraising, the multinational biotech Harbour BioMed pulled in another round of investments and eclipsed the nine-digit mark in the process.

Harbour completed its Series C financing, the company announced Thursday morning, raising $102.8 million and bringing its total investment sum to over $300 million since its founding in late 2016. The biotech plans to use the money to transition early-stage candidates from the discovery phase, fund candidates already in the clinic, and prep late-stage candidates for commercialization.

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Ed Engleman (Stanford Blood Center)

Stan­ford star on­col­o­gy sci­en­tist Ed En­gle­man helped cre­ate the im­munother­a­py field. Now he wants to shake up neu­rode­gen­er­a­tion R&D

Over the last generation of drug R&D, Ed Engleman has been a standout scientist.

The Stanford professor co-founded Dendreon and provided the scientific insights needed to develop Provenge into a pioneering — though not particularly marketable — immunotherapy. He’s spurred a slate of startups, assisted by his well-connected perch as a co-founder of Vivo Capital, and took the dendritic cell story into its next chapter at a startup called Bolt.

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Nello Mainolfi (Kymera via YouTube)

Out to re­vive R&D, a resur­gent Sanofi pays $150M cash to part­ner up with a pi­o­neer­ing pro­tein degra­da­tion play­er

Frank Nestle was appointed Sanofi’s global head of immunology and inflammation research therapeutic area just days before dupilumab, the blockbuster-to-be IL-4 antibody, would be accepted for priority review. After four years of consolidating immunology expertise from multiple corners of the Sanofi family and recruiting new talents to build the discovery engine, he’s set eyes on a Phase I-ready program that he believes can grow into a Dupixent-sized franchise.

Covid-19 roundup: CDC de­bat­ing who should get first avail­able vac­cines; EU in Gilead talks af­ter US gob­bled first remde­sivir dos­es

The federal government has now spent billions of dollars accelerating the development of a Covid-19 vaccine, and yet they’ve remained hush-hush on who, precisely, would actually get inoculated once the first doses are approved and available. Internally, though, they have been debating it.

The CDC and an advisory committee of outside health experts have been working since April to devise a ranking system that would determine who receives a vaccine and when, The New York Times reported. The question of who is first in line for inoculation is important because no matter how many doses developers can make or how quickly they can make them, doses will still come out in batches; 300 million inoculations will not appear overnight.

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Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

A new study points to $6.5B in pub­lic sup­port build­ing the sci­en­tif­ic foun­da­tion of Gilead­'s remde­sivir. Should that be re­flect­ed in the price?

By drug R&D standards, Gilead’s move to repurpose remdesivir for Covid-19 and grab an emergency use authorization was a remarkably easy, low-cost layup that required modest efficacy and a clean safety profile from just a small group of patients.

The drug OK also arrived after Gilead had paid much of the freight on getting it positioned to move fast.

In a study by Fred Ledley, director of the Center for Integration of Science and Industry at Bentley University in Waltham, MA, researchers concluded that the NIH had invested only $46.5 million in the research devoted to the drug ahead of the pandemic, a small sum compared to the more than $1 billion Gilead expected to spend getting it out this year, all on top of what it had already cost in R&D expenses.

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Francis Collins, NIH director (Sean Zanni/Patrick McMullan via Getty Images)

NIH kicks off Covid-19 vac­cine, mon­o­clon­al an­ti­body re­search net­work

The NIH today announced the kickoff of a national clinical trials network to test vaccines and other treatments that could prevent infection with SARS-CoV-2, the virus that causes infection with Covid-19.

The network has been established by the National Institute of Allergy and Infectious Diseases (NIAID) through the merger of four previously existing clinical trials networks that focused on HIV/AIDS.

FDA bars the door — for now — against Mer­ck’s star can­cer drug af­ter Roche beat them to the punch

Merck has been handed a rare setback at the FDA.

After filing for the accelerated approval of a combination of their star PD-1 drug Keytruda with Eisai’s Lenvima as a first-line treatment for unresectable hepatocellular carcinoma, the FDA nixed the move, handing out a CRL because Roche beat them to the punch on the same indication by a matter of weeks.

According to Merck:

Ahead of the Prescription Drug User Fee Act action dates of Merck’s and Eisai’s applications, another combination therapy was approved based on a randomized, controlled trial that demonstrated overall survival. Consequently, the CRL stated that Merck’s and Eisai’s applications do not provide evidence that Keytruda in combination with Lenvima represents a meaningful advantage over available therapies for the treatment of unresectable or metastatic HCC with no prior systemic therapy for advanced disease. Since the applications for KEYNOTE-524/Study 116 no longer meet the criteria for accelerated approval, both companies plan to work with the FDA to take appropriate next steps, which include conducting a well-controlled clinical trial that demonstrates substantial evidence of effectiveness and the clinical benefit of the combination.

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