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.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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Covid-19 roundup: Mer­ck­'s $356M sup­ply deal on hold as FDA asks for more da­ta; UK stud­ies of­fer more in­for­ma­tion on ef­fi­ca­cy of Pfiz­er/BioN­Tech vac­cine af­ter one dose

Merck is pushing back plans to supply the US government with a Covid-19 drug after the FDA asked for more data to support an emergency use authorization.

The antibody, MK-7110, had looked promising in a Phase III study conducted by OncoImmune before Merck came along and bought the biotech for $425 million. At the interim analysis, investigators looked at data from 203 patients and concluded that a single dose of the drug cut the risk of death or respiratory failure by more than 50% among severe patients. And those taking the drug had a 60% higher chance of improvement in clinical status compared to placebo.

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CEO Fred Aslan (Artiva)

NK cell ther­a­py play­er Arti­va makes some more noise, pulling in $120M Se­ries B less than a month af­ter Mer­ck deal

Not even one month after Big Pharma took notice of Artiva when Merck signed a collaboration worth nearly $2 billion in milestones, the off-the-shelf NK cell biotech already has its next big fundraise.

Artiva returns from the venture well Friday with a $120 million Series B round, money they will use to get their first program into the clinic and to file INDs for another two candidates. The raise marks the latest development in a rapidly expanding footprint for Artiva, which, in addition to the Merck deal last month, has now raised almost $200 million since its Series A last June.

Fatty liver conceptual image, 3D illustration showing fatty liver silhouette made from micrograph of liver steatosis (Shutterstock)

The path to NASH: un­der­stand­ing the role of se­vere obe­si­ty in a com­plex, mul­ti-sys­tem dis­ease

Biotech Voices is a collection of exclusive opinion editorials from some of the leading voices in biopharma on the biggest industry questions today. Think you have a voice that should be heard? Reach out to senior editors Kyle Blankenship and Amber Tong.

We often think a person’s transition from a healthy to a diseased state is binary. But that’s often not the case. In reality, the onset of a disease is not something that occurs overnight, and the majority lie on a continuum that is impacted by a multitude of factors. Some of these factors are in a patient’s control. Others are not.

This is the case in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), two of the most complex diseases that “live” on this proverbial continuum. The clinical onset of NAFLD — and ultimately NASH — is a complex process that is closely related to obesity, insulin resistance and impaired adipose tissue metabolism.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

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