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

By: Kyle Blankenship, Managing Editor

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.

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