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.

The FDA will hus­tle up an ex­pe­dit­ed re­view for As­traZeneca’s next shot at a block­buster can­cer drug fran­chise

AstraZeneca paid a hefty price to partner with Daiichi Sankyo on their experimental antibody drug conjugate for HER2 positive breast cancer. And they’ve been rewarded with a fast ride through the FDA, with a straight shot at creating another blockbuster oncology franchise.

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Sean Parker, AP

Sean Park­er helps cre­ate a CRISPRed cell ther­a­py 2.0 play — and he’s got a high-pro­file set of lead­ers on the team

You can rack up one more high-profile debut effort in the wave of activity forming around cell therapy 2.0. It’s another appealing Bay Area group that’s attracted some of the top hands in the business to a multi-year effort to create a breakthrough. And they have $85 million in hand to make that first big step to the clinic.

Today it’s Ken Drazan and the team at South San Francisco-based ArsenalBio that are coming from behind the curtain for a public bow, backed by billionaire Sean Parker and a collection of investors that includes Beth Seidenberg’s new venture investment operation based in LA.
Drazan — a J&J Innovation vet with a long record of entrepreneurial endeavors — exited the stage in 2018 when his last mission ended as he stepped aside as president of Grail. It wasn’t long, though, before he was helping out with a business plan for ArsenalBio that revolved around the work of a large group of interconnected scientists supported by the Parker Institute for Cancer Immunology.
The biotech started by putting together an “arsenal” of technologies aimed at making cell therapies for cancer much, much better than the rather crude first-generation drugs that hit the market from Novartis and Kite.
Their drugs have become the baseline against which all others are being measured.
“The technology set we’re developing is independent of the chassis,” Drazan tells me. “It doesn’t have to be autologous (extracted from the patient) or allogeneic (off the shelf). It doesn’t have to be a T cell, it could be a B cell.” But they are starting out on the autologous side, where they have the most knowledge and insight into manufacturing techniques.
It also doesn’t have to be close to the clinic.
Drazan expects the biotech will be working its way through preclinical operations for “a few years,” with enough money from the $85 million launch round to get into humans.
By today’s superheated fundraising standards, that’s not a huge amount of cash. Lyell, another cell therapy 2.0 startup we featured last week, raised $600 million in a year, including a big chunk of cash from GlaxoSmithKline. Drazan is interested in dealmaking as well, but he also knows he has the cash necessary to support the company for a good run — a key part of what it takes to bring together a stellar team of top players.

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Eli Lil­ly’s first PhI­II show­down for their $1.6B can­cer drug just flopped — what now?

When Eli Lilly plunked down $1.6 billion in cash to acquire Armo Biosciences a little more than a year ago, the stars seemed aligned in its favor. The jewel in the crown they were buying was pegilodecakin, which had cleared the proof-of-concept stage and was already in a Phase III trial for pancreatic cancer.

And that study just failed.

Lilly reported this morning that their cancer drug flopped on overall survival when added to FOLFOX (folinic acid, 5-FU, oxaliplatin), compared to FOLFOX alone among patients suffering from advanced pancreatic cancer.

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Swamy Vijayan. Plexium

San Diego up­start de­buts dis­cov­ery en­gine that puts a twist to pro­tein degra­da­tion

For years, the idea of protein degradation — utilizing the cell’s natural garbage disposal system to mark problematic proteins for destruction — remained an elegant but technically difficult concept. But now established as a promising clinical strategy, with major biopharma players such as Bayer, Gilead and Vertex trying to grab a foothold via partnership deals, a San Diego startup is looking to exploit it and push its limits.

CSL ac­cus­es ri­val Pharm­ing of par­tic­i­pat­ing in a scheme to rip off IP on HAE while re­cruit­ing se­nior R&D staffer

Pharming has landed in the middle of a legal donnybrook after recruiting a senior executive from a rival R&D team at CSL. The Australian pharma giant slapped Pharming with a lawsuit alleging that the Dutch biotech’s new employee, Joseph Chiao, looted a large cache of proprietary documents as he hit the exit. And they want it all back.
Federal Judge Juan Sanchez in the Eastern District Pennsylvania court issued an injunction on Tuesday prohibiting Chiao from doing any work on HAE or primary immune deficiency in his new job and demanding that he return any material from CSL that he may have in his possession. And he wants Pharming to tell its employees not to ask for any information on the forbidden topics.
For its part, Pharming fired off an indignant response this morning denying any involvement in extracting any kind of IP from CSL, adding that it’s cooperating in the internal probe that CSL has underway.

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Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

UP­DAT­ED: Alex­ion pays $930M to buy out Achillion and its promis­ing com­pan­ion drug to Soliris

After a series of stock-crunching setbacks over the years, Achillion enjoyed a turn in the sun a few weeks ago as the FDA blessed their lead drug danicopan (ACH-4471) — a complementary therapy for PNH patients taking Alexion’s Soliris — with a breakthrough drug designation after taking a look at some solid supporting Phase II data.

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The $102B club: The top 15 R&D spenders in the glob­al bio­phar­ma busi­ness — 2019 edi­tion

Over the past few years, the deluge of capital into biotech has helped lead to a dramatic shift in focus on new drug approvals, as startups are now able to raise enough cash to get through a pivotal and onto the market. But the top 15 players still account for $102 billion in spending, and their successes and failures continue to determine just how productive the industry is.

Recently we’ve seen a number of new R&D chiefs take their places at the Big 15, either setting the stage for a more focused R&D strategy — often playing more heavily in oncology. That’s true for AstraZeneca, which has had some landmark successes, and GSK, which is in search of its own turnaround in pharma R&D. HIV and vaccines are separate from that group, now led by Hal Barron.

I’ve made a point of watching their track record every year for more than a decade now. What follows is intended as a broad gauge of their activity. You don’t have to have a lot of major successes to score a winning record here, but it’s virtually impossible without a blockbuster or three in the pipeline.

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