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.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

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Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Rafaèle Tordjman (Jeito Capital)

Con­ti­nu­ity and di­ver­si­ty: Rafaèle Tord­j­man's women-led VC firm tops out first fund at $630M

For a first-time fund, Jeito Capital talks a lot about continuity.

Rafaèle Tordjman had spotlighted that concept ever since she started building the firm in 2018, promising to go the extra mile(s) with biotech entrepreneurs while pushing them to reach patients faster.

Coincidentally, the lack of continuity was one of the sore spots listed in a report about the European healthcare sector published that same year by the European Investment Bank — whose fund is one of the LPs, alongside the American pension fund Teacher Retirement System of Texas and Singapore’s Temasek, to help Jeito close its first fund at $630 million (€534 million). As previously reported, Sanofi had chimed in €50 million, marking its first investment in a French life sciences fund.

Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

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