ATX-101 (APIM Therapeutics)

Planned Phase 2b trial expected to enroll 200 participants at U.S. sites Study design and protocol informed by recent positive discussions with U.S. Food and Drug Administration Prior dose-ranging Phase 2b trial demonstrated durable treatment effects with ATX101 versus standard-of-care bupivacaine based on pain intensity out to four weeks, with less use of opioids for pain relief while achieving faster improvement in function SAN JOSE, Calif.--(BUSINESS WIRE)-- Allay Therapeutics, a clinical-stage biotechnology company pioneering ultra-sustained analgesic products to transform post-surgical pain management and recuperation, today announced plans to proceed to a Phase 2b registration trial of its lead investigational product ATX101. The clinical trial builds on a strong foundation of clinical data from prior exploratory dose-ranging studies and is informed by recent discussions with the U.S. Food and Drug Administration (FDA) on the study design and protocol. If successful, this Phase 2b registration trial would support a new drug application (NDA) filed with the FDA. “We’re excited to reach this important milestone following a productive dialogue with the FDA to establish a clear path forward to evaluating ATX101 and further demonstrating its potential as a post-surgical pain management therapeutic,” said Adam Gridley, Chief Executive Officer at Allay Therapeutics. “The encouraging data from our recently completed Phase 2b dose-ranging trial provide compelling support for our registration clinical trial design, and we look forward to working closely with investigators to fully assess ATX101’s impact on patient recovery and recuperation following total knee replacement.” The Phase 2b registration trial of 200 participants undergoing total knee arthroplasty (replacement, or TKA surgery) will be conducted at multiple U.S. sites and is a three-arm randomized controlled study evaluating treatment with ATX101 1,500 mg versus placebo or a bupivacaine active comparator. The primary endpoint will be the area under the curve (AUC) of pain intensity as measured by the NRS-Rest over several weeks, with secondary endpoints evaluating reduction in use of opioids, opioid-related side effects, and improvement in physical function. The trial will assess and inform additional functional and health economics endpoints for an anticipated global Phase 3 registration study that would support an NDA filing. Allay’s recently completed dose-ranging Phase 2b trial enrolled 112 participants before being concluded early based on a positive interim analysis. Data showed that ATX101 achieved sustained, clinically meaningful post-surgical pain relief for up to four weeks following TKA compared to the standard of care (SOC) active comparator, bupivacaine. Treatment with ATX101 resulted in a decrease in opioid use as well as a decrease in opioid-related side effects and meaningful improvements in functional activities up to 60 days following surgery. About ATX101 ATX101 is a novel investigational configuration of an approved, well-characterized, validated intracellular sodium ion channel blocker, bupivacaine, and a biopolymer that has been designed to provide weeks of pain relief following total knee arthroplasty (TKA, or replacement), a common orthopedic surgery. ATX101 has a high density of drug within its small footprint to allow for ultra-sustained analgesia. It is placed in minutes at the end of standard surgery to deliver its analgesic effect over weeks before eventually dissolving into water and carbon dioxide. The simple procedure does not require specialized training and is intended to replace the existing complex mix of analgesic products used for shorter-term pain management in the post-surgical setting. ATX101 is an investigational product that has not been approved by the U.S. Food and Drug Administration. About Allay Therapeutics Allay Therapeutics is pioneering ultra-sustained analgesic products to transform post-surgical pain management and recuperation for patients and physicians. Our proprietary technology platform combines validated non-opioid analgesics and biopolymers to create dissolvable candidates to deliver pain relief within a targeted site over weeks: an order of magnitude greater than the longest-lasting pain treatments currently available. Our platform and vision were shaped by The Foundry incubator and Lightstone Venture’s Singapore Fund. Allay unites a dynamic, global team of entrepreneurs, scientists, clinicians and innovators in the San Francisco Bay Area and Singapore. Learn more at allaytx.com. View source version on businesswire.com: Contacts For further details: Investors Adam Gridley adam.gridley@allaytx.com Media Chris Railey chris@tenbridgecommunications.com M: +1 617-834-0936 Source: Allay Therapeutics View this news release online at:

Results inform design of pivotal Phase 2B study for potentially first ultra-sustained analgesic product Study concluded early for strong efficacy signals across multiple parameters Clinically meaningful reductions in patient pain relative to standard of care (SOC) observed at timepoints extending to 30 days following total knee replacement Greater reductions in opioid usage seen across four weeks, relative to SOC SAN JOSE, Calif.--(BUSINESS WIRE)-- Allay Therapeutics, a clinical-stage biotechnology company pioneering ultra-sustained analgesic products to transform post-surgical pain management and recuperation, today announced the results from a Phase 2B clinical study of its lead investigational product ATX101. ATX101 achieved sustained post-surgical pain relief for up to four weeks for patients following total knee arthroplasty (replacement, or TKA surgery) and outperformed a standard of care (SOC) active comparator, bupivacaine, on durability of effect, use of opioids to support pain relief and the potential for patients to return to day-to-day activities earlier. The data informs the design of a pivotal Phase 2B study planned to start in 2024. If successful, this study would support a new drug application filed with the U.S. Food and Drug Administration. ATX101 is a novel configuration of a bioresorbable polymer and bupivacaine, an approved injectable non-opioid analgesic drug routinely used in surgeries that provides only one day of pain relief. ATX101 contains a high density of bupivacaine within a biodegradable polymer designed to deliver an ultra-sustained analgesic effect over weeks before dissolving away. “These results support the potential of ATX101’s ability to transform the post-surgical pain management paradigm by delivering non-opioid-based, ultra-sustained pain relief for weeks following knee replacement surgery. Its simple administration has the potential to replace complex and costly existing protocols while providing rapid and extended pain relief over weeks, thereby reducing the burden of these surgeries for patients, physicians and payors alike,” said David Hewitt, M.D., Chief Medical Officer of Allay Therapeutics. “With a growing body of supportive clinical data for ATX101 in TKA, we are highly encouraged regarding the other ultra-sustained product candidates in our portfolio. We thank our investigators, staff and participating patients for helping us deliver this important clinical milestone and gain clear guidance for the design of our pivotal clinical study as we move towards registration.” The study was conducted at 13 sites in Australia, Canada, and the United Kingdom, and enrolled 112 of the planned 165 subjects before being concluded following an interim analysis showing strong efficacy signals related to both pain reduction and need for supplementary opioids relative to the standard of care. These signals were observable despite the modestly sized exploratory study that was not powered to demonstrate statistical significance. The data included: Rapid onset of action and efficacy with ATX101 comparable to bupivacaine SOC over the first 24 hours. A clear dose response on the Numerical Rating Scale for Pain at rest (NRS-R) over time, with clinically meaningful separation of the 1,500mg dose of ATX101 versus bupivacaine SOC through 1, 2 and 3 weeks. Clinically meaningful efficacy signals based on reductions on the primary endpoint, the NRS-R area under the curve (AUC) versus controls over 1, 2, 3 and 4 weeks. These differences reached a nominal significance of p<0.05 at multiple time points. Reduction in opioid consumption with ATX101 versus bupivacaine SOC from Day 2 onward, with more patients opioid-free at earlier time points. Meaningful improvements in a variety of key indicators of function (e.g. activities of daily living) through 30 and 60 days. ATX101 appears to be generally well tolerated with a comparable safety pro bupivacaine SOC. The majority of treatment-emergent adverse events were categorized as mild or moderate. The study compared a single administration of either 1,000 mg (n=37) or 1,500 mg (n=37) dose of ATX101 to a control group (saline placebo (n=4), or bupivacaine SOC (n=34)). Bupivacaine comparator was administered once via local infiltration or adductor canal block. To achieve the required dosage, two or three 500 mg ATX101 implants were placed within the knee capsule prior to surgical closure. The study employed a simplified analgesic regimen in which opioids were used as needed to treat postoperative pain. All patients received around-the-clock celecoxib and acetaminophen to simulate a real-world multimodal analgesic protocol. These data follow an earlier Phase 1B/2A study of ATX101 after TKA surgery which was also concluded early based on efficacy, with top-level data announced in 2021. In addition, extensive nonclinical studies have demonstrated controlled delivery, safety and tolerability of ATX101. “Our hope was that the data from this study would demonstrate that patients can mobilize and rehabilitate more quickly, without the challenges of today’s standard of care, which only provides one day of pain relief with variable results and leaves patients with limited, often opioid-based solutions to manage their pain,” said Prof. Hemant Pandit, M.D., Ph.D., an expert in hip and knee joint replacement surgery at the University of Leeds and Leeds Teaching Hospitals NHS Trust, United Kingdom, and a leading investigator in this study. “The simplicity of the ATX101 procedure, which takes only two minutes to place with no special training, also has no equivalent among today’s local analgesic options. Indeed, the data from this multi-center, multi-national study supports the ability of ATX 101 to consistently deliver pain relief over a prolonged period, reducing the need for use of opioids and shortening the time needed to recover, allowing patients to return to day-to-day activities earlier than expected.” TKA surgery is performed over one million times each year in the United States and the number of procedures is growing rapidly with the aging population. It is associated with a lengthy, painful recovery often managed with significant opioid usage and associated adverse events. The total addressable market for post-TKA pain management in the United States is estimated to be approximately $1 billion. Currently, approved post-surgical pain products last only 3-4 days at most, are often challenging to administer consistently, deliver variable outcomes and are insufficient to fully support the days and weeks of recuperation. This often results in supplementary opioid use and extended recovery, all resulting in significant additional healthcare cost burdens as well as significant risk of opioid abuse and addiction. About ATX101 ATX101 is a novel investigational configuration of an approved, well-characterized, validated intracellular sodium ion channel blocker, bupivacaine, and a biopolymer that has been designed to provide weeks of pain relief following total knee arthroplasty (TKA, or replacement), a common orthopedic surgery. ATX101 has a high density of drug within its small footprint to allow for ultra-sustained analgesia. It is placed in minutes at the end of standard surgery to deliver its analgesic effect over weeks before eventually dissolving into water and carbon dioxide. The simple procedure does not require specialized training and is intended to replace the existing complex mix of analgesic products used for shorter-term pain management in the post-surgical setting. ATX101 is an investigational product that has not been approved by the U.S. Food and Drug Administration. About Allay Therapeutics Allay Therapeutics is pioneering ultra-sustained analgesic products to transform post-surgical pain management and recuperation for patients and physicians. Our proprietary technology platform combines validated non-opioid analgesics and biopolymers to create dissolvable candidates to deliver pain relief within a targeted site over weeks: an order of magnitude greater than the longest-lasting pain treatments currently available. Our platform and vision were shaped by The Foundry incubator and Lightstone Venture’s Singapore Fund. Allay unites a dynamic, global team of entrepreneurs, scientists, clinicians and innovators in the San Francisco Bay Area and Singapore. Learn more at allaytx.com. View source version on businesswire.com: Contacts Investors Adam Gridley adam.gridley@allaytx.com Media Chris Railey chris@tenbridgecommunications.com M: +1 617-834-0936 Source: Allay Therapeutics View this news release online at: