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.

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

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Vas Narasimhan (Photographer: Jason Alden/Bloomberg via Getty Images)

No­var­tis de­tails plans to axe 8,000 staffers as Narasimhan be­gins sec­ond phase of a glob­al re­org

We now know the number of jobs coming under the axe at Novartis, and it isn’t small.

The pharma giant is confirming a report from Swiss newspaper Tages-Anzeiger that it is chopping 8,000 jobs out of its 108,000 global staffers. A large segment will hit right at company headquarters in Basel, as CEO Vas Narasimhan axes some 1,400 of a little more than 11,000  jobs in Switzerland.

The first phase of the work is almost done, the company says in a statement to Endpoints News. Now it’s on to phase two. In the statement, Novartis says:

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Lina Gugucheva, NewAmsterdam Pharma CBO

Phar­ma group bets up to $1B-plus on the PhI­II res­ur­rec­tion of a once dead-and-buried LDL drug

Close to 5 years after then-Amgen R&D chief Sean Harper tamped the last spade of dirt on the last broadly focused CETP cholesterol drug — burying their $300 million upfront and the few remaining hopes for the class with it — the therapy has been fully resurrected. And today, the NewAmsterdam Pharma crew that did the Lazarus treatment on obicetrapib is taking another big step on the comeback trail with a €1 billion-plus regional licensing deal, complete with close to $150 million in upfront cash.

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How pre­pared is bio­phar­ma for the cy­ber dooms­day?

One of the largest cyberattacks in history happened on a Friday, Eric Perakslis distinctly remembers.

Perakslis, who was head of Takeda’s R&D Data Sciences Institute and visiting faculty at Harvard Medical School at the time, had spent that morning completing a review on cybersecurity for the British Medical Journal. Moments after he turned it in, he heard back from the editor: “Have you heard what’s going on right now?”

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Pearl Huang, Dunad Therapeutics CEO (Ken Richardson, PR Newswire)

Long­time biotech leader Pearl Huang takes the reins as CEO of No­var­tis-backed up­start

It has only been a few months since Pearl Huang exited the top seat at Cygnal Therapeutics, but now she’s back at the helm of another biotech.

After taking a few months off — passing an exam in that time to get her captain’s license from the US Coast Guard — she’s been named CEO of Dunad Therapeutics, a biotech focused on developing a small molecule covalent therapies that was founded in 2020. Huang told Endpoints News that two factors attracted her to going back to the c-suite: the company’s technology and its co-founders.

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(AP Photo/Gemunu Amarasinghe)

Some phar­ma com­pa­nies promise to cov­er abor­tion-re­lat­ed trav­el costs — while oth­ers won't go that far yet

As the US Department of Health and Human Services promises to support the millions of women who would now need to cross state lines to receive a legal abortion, a handful of pharma companies have said they will pick up employees’ travel expenses.

GSK, Sanofi, Johnson & Johnson, BeiGene, Alnylam and Gilead have all committed to covering abortion-related travel expenses just four days after the Supreme Court overturned Roe v. Wade and revoked women’s constitutional right to an abortion.

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Aurobindo Pharma co-founders P. V. Ram Prasad Reddy (L) and K. Nityananda Reddy

Au­robindo Phar­ma re­ceives warn­ing let­ter from In­di­a's SEC fol­low­ing more FDA ques­tion marks

Indian-based generics manufacturer Aurobindo Pharma has been in the crosshairs of the FDA for several years now, but the company is also attracting attention from regulators within the subcontinent.

According to the Indian business news site Business Standard, a warning letter was sent to the company from the Securities Exchange Board of India, or SEBI.

The letter is related to disclosures made by the company on an ongoing FDA audit of the company’s Unit-1 API facility in Hyderabad, India as well as observations made by the US regulator between 2019 and 2022.

New Charles River Laboratories High Quality (HQ) Plasmid DNA Centre of Excellence at Bruntwood SciTech’s Alderley Park in Cheshire, United Kingdom. (Charles River)

Charles Riv­er Lab­o­ra­to­ries to start cell and gene ther­a­py man­u­fac­tur­ing at UK site in Sep­tem­ber

While Massachusetts-based Charles River Laboratories has been on an acquisition spree, they are not against planting their flag. The latest move by the company sees them crossing the pond to establish a manufacturing site in the UK.

The company on Tuesday opened its cell and gene therapy manufacturing center at Bruntwood SciTech’s Alderley Park in Cheshire, United Kingdom. The expansion follows Charles River’s acquisition of Cognate BioServices and Cobra Biologics in 2021 for $875 million. Cognate is a plasmid DNA, viral vector and cell therapy CDMO.

Bristol Myers Squibb (Alamy)

CVS re­sumes cov­er­age of block­buster blood thin­ner af­ter price drop fol­lows Jan­u­ary ex­clu­sion

Following some backlash from the American College of Cardiology and patients, Bristol Myers Squibb and Pfizer lowered the price of their blockbuster blood thinner Eliquis, thus ensuring that CVS Caremark would cover the drug after 6 months of it being off the major PBM’s formulary.

“Because we secured lower net costs for patients from negotiations with the drug manufacturer, Eliquis will be added back to our template formularies for the commercial segment effective July 1, 2022, and patient choices will be expanded,” CVS Health said in an emailed statement. “Anti-coagulant therapies are among the non-specialty products where we are seeing the fastest cost increases from drug manufacturers and we will continue to push back on unwarranted price increases.”