Adam Gridley, Allay Therapeutics CEO

A non-opi­oid pain start­up be­lieves it can top the bupi­va­caine mar­ket — and it's think­ing in terms of weeks, not days

The road to non-opi­oid pain man­age­ment has swal­lowed biotech play­ers for years as drug de­vel­op­ers have smacked their heads against safe­ty flags. A Cal­i­for­nia biotech that spent a long time work­ing in stealth mode now has ear­ly da­ta sug­gest­ing it may have found a break­through — and the com­pa­ny is ready for its close-up.

Al­lay Ther­a­peu­tics launched Thurs­day with Phase I da­ta show­ing their poly­mer­ized bupi­va­caine im­plant helped 80% of pa­tients get off opi­oids 14 days af­ter a to­tal knee re­place­ment, the com­pa­ny said.

The biotech, found­ed in 2017 by The Foundry in­cu­ba­tor and Light­stone Ven­tures’ Sin­ga­pore fund, looks to craft tai­lored-re­lease ther­a­pies for long-last­ing pain man­age­ment with­out the need for ag­gres­sive opi­oid use af­ter surgery. Its lead com­pound, ATX-101, is a quar­ter-sized im­plant that re­leas­es lo­cal anal­gesic bupi­va­caine com­bined with pro­pri­etary biopoly­mers to match pa­tients’ pain lev­els in the days and weeks af­ter a knee re­place­ment.

Ac­cord­ing to da­ta from a Phase Ib/IIa dose-es­ca­la­tion study in 22 Aus­tralian pa­tients, ATX-101 cut the num­ber of opi­oids pa­tients took af­ter 14 days by half to two-thirds com­pared with stan­dard of care and place­bo. Mean­while, 80% of pa­tients were off opi­oids at the 14-day mark com­pared to around 50% on stan­dard of care.

In terms of pain score, ATX-101 “sig­nif­i­cant­ly out­per­formed” stan­dard of care in terms of du­ra­tion and mag­ni­tude of ef­fect, Al­lay said, and kept pa­tients’ pain in the “ze­ro to mild range” for at least two weeks. Mean­while, pa­tients on stan­dard of care tend to have se­vere short-term pain fol­lowed by mod­er­ate pain for weeks.

Even more promis­ing­ly, the im­plant showed “mean­ing­ful sys­temic lev­els” of bupi­va­caine in pa­tients af­ter 14 days, where­as oth­er bupi­va­caine-based treat­ments are no longer de­tectable af­ter five days, Al­lay said.

Those re­sults are promis­ing enough for Al­lay, which is plot­ting a 300-pa­tient Phase IIb study in the US by the end of the year and set­ting its sights on a fol­low-up Phase III study and pos­si­ble NDA by 2024. That study will test pa­tients on the two high­est dos­es in the Phase I — 750 mg and 1,500 mg.

Crack­ing the code on last­ing non-opi­oid pain man­age­ment has left a slew of wrecked biotechs in re­cent years, but Al­lay thinks its plat­form can churn out tun­able im­plants that pro­vide last­ing pain al­le­vi­a­tion with­out the side ef­fects com­mon to sus­tained high use of lo­cal anes­thet­ics, CEO Adam Gri­d­ley told End­points News. The ATX-101 im­plant car­ries 70 times the drug den­si­ty of oth­er drug-poly­mer con­fig­u­ra­tions, a mas­sive pay­load that sets Al­lay’s prod­uct apart, Gri­d­ley said.

There are, of course, oth­er play­ers in this game, but those ther­a­pies work on the scale of days, not weeks. In Feb­ru­ary, the FDA ap­proved Durect’s 72-hour bupi­va­caine so­lu­tion Posimir for use af­ter shoul­der surgery. Mean­while, Heron is await­ing FDA ap­proval for its 72-hour for­mu­la dubbed HTX-011, and Paci­ra is chas­ing its own can­di­date.

So what is Al­lay bring­ing new? Well, it’s not bupi­va­caine or the biopoly­mers used in the im­plant, but in­stead the way the im­plant is man­u­fac­tured that gives it an edge, CTO Patrick Ru­ane told me.

“We’re re­al­ly stand­ing on the shoul­ders of gi­ants — us­ing drugs that are well-es­tab­lished, us­ing poly­mers that are off the shelf,” Ru­ane said. “It’s re­al­ly how we con­fig­ure it and put it to­geth­er. There’s some re­al­ly neat man­u­fac­tur­ing tech­niques where we can con­trol it, and that’s val­i­dat­ed in our clin­i­cal da­ta that it re­al­ly does work.”

Af­ter years in de­vel­op­ment and a raft of ear­ly ex­per­i­ments in the rearview — rough­ly 203, to be ex­act — Al­lay wait­ed un­til it was sure its Phase I tri­al was a suc­cess to un­cloak. There were a num­ber of rea­sons for that de­lay, Gri­d­ley said, but the biggest was be­ing able to prove to in­vestors ear­ly that the plat­form could show promise where so many oth­ers have failed.

“It re­al­ly was, let’s make sure we got some­thing be­fore we come out of stealth,” he said. “This has been such a hard area, no one has got­ten past a cou­ple of days at least do­ing so safe­ly, so that’s where the com­pa­ny has his­tor­i­cal­ly just been pret­ty qui­et. It was that abil­i­ty to show in the most re­cent clin­i­cal tri­al that we were on to some­thing that pre­cip­i­tat­ed the com­ing-out par­ty.”

But now, with the cork popped, Al­lay is ready to make a quan­tum leap for­ward.

On top of its ramped-up clin­i­cal plans for ATX-101, Al­lay has a pipeline un­der de­vel­op­ment to take its drug-biopoly­mer com­bos in­to oth­er post-sur­gi­cal set­tings — in­clud­ing hips, shoul­ders, bunions and her­nias, to count a few — as well as look­ing at a sec­ond-gen fol­low-up to ATX-101. The clin­i­cal pro­gram al­so in­cludes more pa­tient-friend­ly for­mu­la­tions, in­clud­ing an in­jectable.

Mean­while, the biotech is al­so work­ing on what Ru­ane called its “moon­shot” — a re­mote-con­trolled im­plant that would al­low pa­tients and physi­cians to di­al up or down an anes­thet­ic based on pain lev­el with a tap of a phone screen. That par­tic­u­lar project is a ways off, but Al­lay plans to add one new can­di­date in­to hu­man tri­als each year, Gri­d­ley said.

The team will al­so look to great­ly ex­pand in the com­ing years as it ap­proach­es a po­ten­tial NDA, go­ing from its cur­rent work­force of about 40 — 25 in the US and 15 in Sin­ga­pore — to more than 50 by the end of the year. In the next few years, Gri­d­ley said, the biotech could dou­ble in size as it brings more prod­ucts in­to the clin­ic.

In the short term, how­ev­er, Al­lay is look­ing to bring on a chief med­ical of­fi­cer as well as build out its clin­i­cal and sci­en­tif­ic ad­vi­so­ry boards. Pri­or to emerg­ing from stealth, the biotech re­lied on fund­ing from The Foundry and Light­stone from seed to Se­ries B, but Gri­d­ley said Al­lay is cur­rent­ly look­ing to piece to­geth­er a $60 mil­lion Se­ries C to ad­vance its lead pro­gram, with new in­vestors hope­ful­ly jump­ing on board.

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Barry Greene, Sage CEO

UP­DAT­ED: Sage's sec­ond chance at de­pres­sion hits the PhI­II pri­ma­ry, but ques­tions re­main over dura­bil­i­ty, side ef­fects

Looking to make a comeback after a big Phase III flop, Sage Therapeutics revealed data they believe could change the entire depression treatment landscape, given the vast array of failures in the field. But some results are spooking investors, sending Sage $SAGE shares down early Tuesday.

First, the primary: Sage and Biogen reported Phase III data for once-daily zuranolone Tuesday morning, saying the experimental drug hit its primary endpoint by spurring a statistically significant change from baseline in the 17-item Hamilton Rating Scale for Depression total score. After 15 days, patients in the drug arm saw an average change of -14.1 points, compared to -12.3 on placebo.

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Michel Sade­lain puts his name and new cell en­gi­neer­ing tech be­hind 'ag­nos­tic' CAR-T start­up chas­ing epi­ge­net­ic anti­gens

It felt natural for Alain Maiore and Sebastian Amigorena to bring in Michel Sadelain as a co-founder of Mnemo Therapeutics. A CAR-T pioneer, Sadelain had been involved as an advisor since the early days — enthusiastic about Amigorena’s work in a genetic knockout that could enhance T cell memory and a new class of potential targets he’s discovered — and could introduce some well-known technologies to the toolbox. So they got the initial cash from Sofinnova Partners to plant roots in Paris and New York in early 2019; within a few months, they began to see more clearly just what the antigen discovery platform might unlock.

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Bio­gen sig­nals a big PhI­II fail­ure as the lead gene ther­a­py in their $800M Night­star buy­out goes down in flames

That $800 million buyout of Nightstar has turned into a bust for Biogen as the lead therapy in the deal failed a pivotal study, signaling a severe setback for the biotech’s ambitions in gene therapies.

The big biotech put out the word after the market closed on Monday that the gene therapy they picked up in the deal for a degenerative blindness called choroideremia failed the Phase III study, just a month after their #2 drug in the deal also flopped in a mid-stage study.

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CEO Harith Rajagopalan (Fractyl)

Af­ter a decade in the type 2 di­a­betes game, Fractyl Lab­o­ra­to­ries recharges with a fresh $100M and a new name

Harith Rajagopalan compared the way type 2 diabetes is managed to sticking your fingers in a dam that’s leaking from a number of places.

You can take drugs to lower your blood sugar, cholesterol, or blood pressure, but you’re not addressing what he says is the core issue — the metabolic abnormality that causes the disease.

“We’re so busy plugging the holes in the dam, we don’t have time to see that the whole infrastructure is at risk,” he said. “That infrastructure is a full-body systemic metabolic abnormality called metabolic syndrome, that we’re ignoring while we’re so busy trying to treat all of the individual symptoms of the condition.”

Lynn Fitch, Mississippi Attorney General (Rogelio V. Solis/AP Images)

Mis­sis­sip­pi sues Eli Lil­ly, Sanofi and No­vo over in­sulin prices as in­ter­change­able biosim­i­lars may ar­rive soon

Mississippi Attorney General Lynn Fitch last week sued the top three insulin manufacturers, which collectively cover almost the entire US insulin market, alleging that they’ve colluded to raise their prices in lockstep, and in some cases by more than 1,000% for drugs that are decades old.

“Because of Manufacturer Defendants’ collusive price increases, nearly a century after the discovery of insulin, diabetes medications have become unaffordable for many diabetics,” the lawsuit says.

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Andrew Hopkins, Exscientia CEO

Ex­sci­en­tia spends Soft­Bank's cash in bid to edge out AI ri­vals

Exscientia is sprinting to win the great AI biotech race.

The UK company, having long labored on small discovery deals with large pharmas, raised up to $525 million in a Series D led by the infamous Japanese conglomerate SoftBank in April and followed it up less than a month later with a Bristol Myers Squibb deal that paid $50 million cash and $1.2 billion in milestones.

Now, the Oxford spinout is splurging on a shiny new tool. On Monday they announced they purchased the three-year-old molecule-screening biotech Allcyte, a longtime collaborator, for $60.6 million in cash and stock.

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Hal Barron, GSK R&D chief (Endpoints News)

Hal Bar­ron gam­bles $625M cash on high-wire TIG­IT act, throw­ing Glax­o­SmithK­line in­to heat­ed race and com­plet­ing next-gen I/O trin­i­ty

Count Hal Barron and GlaxoSmithKline in for the TIGIT fight.

The stakes are as high as the risks: While a growing pack of Big Pharma rivals is lending credence to the hypothesis that TIGIT will be the next big immune checkpoint and cancer drug target, the first clinical trials have shown response rates that can be described as modest at best. But Barron’s bet is on the whole “axis” that the receptor sits on, with an eye on testing its new anti-TIGIT antibody not just in combo with PD-1 but also in triplets.

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As Covid-19 shifts the world's at­ten­tion to biotech, Noubar Afeyan's Flag­ship builds $3.4B fund to fu­el new in­ven­tions. Here's the plan

A little more than a year ago, Flagship Pioneering rolled out a monster fund with $1.1 billion in it to bankroll the platform companies they were creating inside their own labs. But it turns out, that was just the prelude to a much, much larger raise, as both current investors — who’ve been reaping the rewards of some booming biotech stocks — join in with new investors betting on more in the years to come.

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