Left for dead af­ter a fail­ure in neu­ro­path­ic pain, Aptinyx latch­es on­to pos­i­tive PhII da­ta in PTSD

Al­most two years af­ter a Phase II fail sent in­vestors run­ning for the hills, Aptinyx $AP­TX may have found a new life­line.

The Evanston, IL-based biotech, which fo­cus­es on brain and cen­tral ner­vous sys­tem dis­or­ders, an­nounced pos­i­tive Phase II da­ta in post-trau­mat­ic stress dis­or­der Mon­day af­ter­noon with one of its NM­DA re­cep­tor mod­u­la­tors. Armed with the topline ef­fi­ca­cy and safe­ty re­sults, Aptinyx now plans to be­gin a piv­otal study some­time in 2021.

Nor­bert Riedel

“We are very pleased with these im­pres­sive re­sults, which sur­passed our ex­pec­ta­tions for this ini­tial ex­plorato­ry study,” CEO Nor­bert Riedel said in a state­ment.

Aptinyx’s shares near­ly dou­bled af­ter the bell Mon­day, soar­ing as high as 96% less than two hours af­ter the com­pa­ny re­port­ed the da­ta.

The dri­ving force be­hind this re­bound is a pro­gram called NYX-783, an oral NM­DA re­cep­tor mod­u­la­tor. De­signed to en­hance what’s known as ex­tinc­tion learn­ing, Aptinyx says NYX-783 can al­le­vi­ate symp­toms of the con­di­tion such as ir­ri­tabil­i­ty, ag­gres­sion, reck­less or self-de­struc­tive be­hav­ior and lack of con­cen­tra­tion.

NYX-783 was stud­ied in a place­bo-con­trolled, dou­ble-blind­ed and ran­dom­ized tri­al with 153 pa­tients. The Phase II took place over two four-week stages and mea­sured two dif­fer­ent dos­es, 10 mg and 50 mg, both of which showed sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ments (p=0.049 and p=0.040, re­spec­tive­ly) on the CAPS-5 Arousal and Re­ac­tiv­i­ty Score, a clin­i­cian-ad­min­is­tered in­ter­view de­signed to eval­u­ate PTSD pa­tients.

Aptinyx al­so re­port­ed CAPS-5 To­tal Score da­ta from the first stage of the Phase II, which it said showed clin­i­cal­ly mean­ing­ful im­prove­ments that trend­ed to­ward sig­nif­i­cance. In the drug arm, 78% of pa­tients tak­ing the 50 mg dose achieved a 30% im­prove­ment from base­line af­ter four weeks, com­pared to 44% tak­ing place­bo (p=0.008). With­in the same arm, 50% of pa­tients saw a 50% im­prove­ment from base­line against 26% on place­bo (p=0.044).

The pri­ma­ry end­point of the study was the change in CAPS-5 To­tal Score and sub­scores for Stage 1 and Stage 2, com­bined as weight­ed ef­fects.

In a con­fer­ence call with in­vestors Tues­day morn­ing, Aptinyx elab­o­rat­ed on the da­ta and em­pha­sized that in Stage 1, two-thirds of the pa­tient pop­u­la­tion was ran­dom­ized in­to place­bo. As the tri­al moved in­to Stage 2 af­ter four weeks, all of the pa­tients in the orig­i­nal drug arm were placed in­to place­bo, and the orig­i­nal place­bo group was di­vid­ed in­to re­spon­ders and non-re­spon­ders. Each group was then ran­dom­ized for the next four-week pe­ri­od to re­ceive place­bo, the 10 mg dose or the 50 mg dose at a 2:1:1 rate.

Aptinyx sci­en­tists stressed on the call that this en­sured no in­di­vid­ual re­ceived more than four weeks of treat­ment at any point.

SVBLeerink’s Marc Good­man pegged this as a good sign for Aptinyx, writ­ing to in­vestors:

The stock has been in the “penal­ty box” since the neg­a­tive Phase 2 read­out of its lead­ing as­set NYX-2925 in painful di­a­bet­ic pe­riph­er­al neu­ropa­thy over a year ago, which has re­sult­ed in in­creased in­vestor skep­ti­cism re­gard­ing its NM­DA mod­u­la­tion plat­form, so this is very wel­come news which should help re­ju­ve­nate con­fi­dence in this MoA. Giv­en how neg­a­tive in­vestor sen­ti­ment has been, we are not sur­prised to see the stock up >80% in af­ter-mar­ket trad­ing.

Ex­tinc­tion learn­ing it­self is a psy­cho­log­i­cal phe­nom­e­non that’s used to re­con­di­tion the brain in re­sponse to cer­tain stim­uli. Specif­i­cal­ly, it refers to the de­creas­ing re­sponse to a known stim­u­lus when it’s pre­sent­ed with­out re­in­force­ment. Think Pavlov’s dog: af­ter the dog was trained to sali­vate at the sound of a bell, Pavlov be­gan ring­ing the bell with­out giv­ing any food. Soon, the dog stopped sali­vat­ing.

Sim­i­lar meth­ods are used to help PTSD pa­tients dis­as­so­ci­ate from their fears. NYX-783 boosts this ac­tiv­i­ty, Aptinyx says, mod­u­lat­ing the NM­DA re­cep­tor to dri­ve ac­tiv­i­ty to por­tions of the brain where pa­tients have al­tered con­nec­tiv­i­ty when re­call­ing trau­mat­ic events.

Mon­day’s news could mark the start of a turn­around for the biotech af­ter their pro­gram for di­a­bet­ic pe­riph­er­al neu­ropa­thy flopped hard back in Jan­u­ary 2019. The for­mer lead can­di­date, an­oth­er NM­DA re­cep­tor mod­u­la­tor, failed to meet the pri­ma­ry end­point in a Phase II in any of the three dos­es be­ing test­ed, send­ing their stock price plum­met­ing 70%. Af­ter mak­ing its pub­lic de­but in June 2018 at $20 per share, Aptinyx has trad­ed be­low $6 ever since that bust.

PTSD has proved a no­to­ri­ous­ly tough in­di­ca­tion to crack, and NM­DA pro­grams test­ed in oth­er fields have not seen much suc­cess ei­ther. Al­ler­gan bought out Nau­rex for $560 mil­lion sev­er­al years ago hop­ing to uti­lize its ex­per­i­men­tal NM­DA drugs to treat de­pres­sion, but that led to a Phase III dud in March 2019.

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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GSK, Vir's hopes for a Covid-19 an­ti­body fall flat in NIH 'mas­ter pro­to­col' with no ben­e­fit in hos­pi­tal­ized pa­tients

GlaxoSmithKline and Vir Biotechnology were hopeful that one of their partnered antibodies would carve out a win after getting the invite to a major NIH study in hospitalized Covid-19 patients. But just like Eli Lilly, the pair’s drug couldn’t hit the mark, and now they’ll be left to take a hard look at the game plan.

The NIH has shut down enrollment for GSK and Vir’s antibody VIR-7831 in its late-stage ACTIV-3 trial after the drug showed negligible effect in achieving sustained recovery in hospitalized Covid-19 patients, the partners said Wednesday.

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As Brain­Storm con­tin­ues to tout ‘clear sig­nal’ on ALS drug, the FDA of­fers a rare pub­lic slap­down on the da­ta

A little more than a week after BrainStorm acknowledged that regulators at the FDA had informed them that the biotech needed more data before it could expect to gain an approval for its ALS treatment NurOwn — while still touting a “clear signal” of efficacy and not ruling out an application — the agency has decided to clarify the record in a most unusual statement.

The FDA statement amounts to a straight slap own, offering a different set of efficacy numbers from the company’s public presentation last November and ruling out any chance of statistical significance.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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Eli Lil­ly claims suc­cess in a new JAK in­di­ca­tion: hair loss

Over the last decade, drugmakers have proven JAK inhibitors can treat a smattering of immune-related diseases ranging from rheumatoid arthritis to Covid-19. Now Eli Lilly has pulled out a new one.

Lilly and its biotech partner Incyte announced Wednesday that their JAK inhibitor baricitinib effectively regrew patients’ hair in a Phase III trial for alopecia areata, an autoimmune condition that can cause sudden, severe and patchy hair loss. Lilly didn’t break down the results from the 546-patient trial, but the primary endpoint was improvement on a standard score for alopecia symptoms.

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In­tro­duc­ing End­points FDA+, our new pre­mi­um week­ly reg­u­la­to­ry news re­port led by Zachary Bren­nan

CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means.

Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society.

Antoine Papiernik, Sofinnova managing director (Business Wire)

Sofinno­va Part­ners stays fo­cused on late-stage deals with a new, $540M crossover fund

One of Europe’s most high-profile biopharma investors is getting $540 million to invest in new crossover deals for late-stage companies.

The Paris-based VC says the fresh Sofinnova Crossover Fund raise positions them as the “largest crossover investor in Europe dedicated to late-stage biopharma and medtech investments.”

They got a leg up in France after winning a special “Tibi” designation from the French government, giving them access to a pool of €6 billion that helped them gain an edge with institutional investors. Since they were founded close to 50 years ago, the venture group has backed more than 500 companies and currently has more than €2 billion under management.

Presage teams with Mer­ck on its Phase 0 test­ing; Kem­Pharm AD­HD drug wins ap­proval in chil­dren aged 6 and up

Seattle-based Presage Biosciences, which approaches drug development through its microdosing platform, has some new partnerships and cash to come with them.

Presage closed a $13 million financing round Tuesday, aiming to expand its network of clinical trial sites and advance development of its microdosing injection devices. They also closed partnership deals with Merck and Maverick Therapeutics.

The financing included $7 million from new investors, including the LabCorp Venture Fund, Bristol Myers Squibb, and InHarv Partners. An additional $6 million convertible note from Takeda Ventures will convert to equity.

Thank you, next: Take­da hands Ovid $196M cash to rein back in Phase III-ready seizure drug, re­viv­ing bat­tered stock

Soticlestat made it.

Takeda is bringing the drug back into its fold more than four years after first entrusting the team at Ovid with the mid-stage clinical work. For all that — generating what they saw as positive Phase II data in Dravet syndrome and Lennox-Gastaut syndrome — the biotech has been rewarded with $196 million in upfront cash, with another $660 million reserved for regulatory and commercial milestones.

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