Adolore BioTherapeutics Announces Publication of Compelling Preclinical Efficacy and Safety Data Supporting Adolore's Non-opioid Analgesic Gene Therapy, ADLR-1001, For Treatment of Moderate to Severe Chronic Knee Pain Due to Osteoarthritis (OA)

This publication validates Adolore's approach for the intracellular delivery of a non-opioid analgesic minigene to targeted sensory neurons via local administration

Data provide a robust preclinical proof-of-concept for this JDNI8-rdHSV-based carbonic anhydrase-8 (vHCA8*) intracellular minigene delivery as a ‘chronic pain disease-modifying' long-acting local analgesic

Data further support the clinical-translational value of these findings for treating human chronic pain without opioids

Company continues to progress with IND-enabling studies of ADLR-1001 gene therapy for the treatment of chronic knee pain due to OA with support from a NIH/NINDS UH3 HEAL Grant; Additional translational data are expected before year-end

DELRAY BEACH, FL / ACCESSWIRE / July 30, 2024 / Adolore BioTherapeutics ("Adolore" or the "Company"), a biotechnology company focused on developing breakthrough opioid-free gene therapy treatments for chronic pain, today announced the publication of its manuscript entitled, "Disease-Modifying rdHSV-CA8* Non-Opioid Analgesic Gene Therapy Treats Chronic Osteoarthritis Pain by Activating Kv7 Voltage-Gated Potassium Channels[1], " in the peer-reviewed journal, Frontiers in Molecular Neuroscience.

This manuscript, co-authored by Roy Clifford Levitt, MD, Clinical Professor at the University of Miami, Principal Investigator and Program Director of the NIH, NINDS, HEAL Award supporting ADLR-1001 development for the treatment of chronic knee pain due to OA, and Founder, Executive Chairman & Chief Medical Officer of Adolore BioTherapeutics, highlighted data from preclinical studies testing the hypothesis that a novel JDNI8 replication-defective herpes simplex-1 viral vector (rdHSV) incorporating a modified carbonic anhydrase-8 (CA8*) minigene (shortened version of gene within rdHSV that expresses CA8* and is not integrated into the recipients genome) produces potent analgesia and treats chronic knee pain due to OA in a monoiodoacetate-induced (MIA) preclinical model. Prolonged dose-dependent therapeutic effects of Intra-Articular (IA) Knee-Joint (KJ) administration of vHCA8* on MIA-induced chronic KJ pain due to OA are consistent with the specific activation of Kv7 channels in small DRG sensory neurons. Together, these data demonstrate for the first-time that local IA KJ administration of vHCA8* produces highly potent opioid-independent analgesia due to severe OA in this model, supporting further therapeutic development.

Dr. Levitt commented, "Kv7 channels remain important analgesic targets. Kv7 voltage-gated potassium channel openers are well-known to produce non-opioid-based analgesia in various animal models and human chronic pain conditions. Based on these data, a single KJ injection of vHCA8* provided profound, prolonged analgesia and normalized the negative impact of OA pain on weight-bearing and voluntary activity. The vHCA8*-induced analgesic mechanism of action is described in this paper. Bolstered by these data, we are continuing the development of our highly innovative and transformational intracellular CA8* minigene therapy toward the clinic to address the significant unmet need for safe and effective pain therapies to replace opioids."

Key Highlights

• This vHCA8*-induced analgesic mechanism of action was shown to result from the specific activation of Kv7 voltage-gated potassium channels in smaller sensory neurons, encoded by KCNQ genes.

• Nerve, skin and KJ injections were all effective vHCA8* dosing routes.

• No drug-related adverse events or clinical safety concerns were observed with KJ injections of vHCA8*. Joint cartilage was unchanged in healthy animals; and weight-bearing and voluntary activity were normalized with vHCA8* IA KJ treatment in MIA-exposed animals.

• rdHSV is a revolutionary nontoxic and disease-free platform technology that enables the intracellular delivery of minigenes coding for biological therapies relevant to large chronic pain populations. This approach differentiates it from other types of gene therapy used mainly for treating rare diseases.

• These data provide a compelling preclinical proof-of-concept for the intracellular delivery of a vHCA8* minigene representing a ‘chronic pain disease-modifying' long-acting local analgesic with the potential to replace opioids for treating chronic pain due to knee OA.

Leveraging its innovative rdHSV platform for intracellular delivery of its CA8*(*Carbonic anhydrase-like analgesic minigene coding for a modified CA8* peptide variants), ADLR-1001, Adolore is currently advancing two development programs. ADB-101 for the treatment of patients' life-long recurrent chronic pain caused by erythromelalgia, a serious and debilitating orphan disease, and ADB-102 - Adolore's lead program - for the treatment of patients with chronic moderate-to-severe knee pain caused by OA. Based on very compelling preclinical data generated to date, the Company is progressing these programs toward IND filings and first-in-human clinical studies.

The Company's development program for ADLR-1001 is licensed worldwide for the treatment of chronic pain, and the NIH/NINDS HEAL UH3 Award fully funds all formal preclinical GLP/GMP/GCP development through a first-in-human (FIH) clinical study in patients. This FIH clinical study is expected to commence in 2026.

About Carbonic Anhydrase-8 (CA8*) Gene Therapy

CA8* (*Carbonic anhydrase-8 like analgesic peptides, CA8 variants), delivered as intracellular non-genome integrative minigene therapies, are a novel class of long-acting, locally administered, neuronal calcium channel inhibitors that activate Kv7 voltage-gated potassium channels. Oral therapeutics that activate Kv7 voltage-gated potassium channels demonstrated proven analgesic efficacy before they were removed from the market due to severe adverse events related to systemic exposure. CA8* intracellular minigene therapy provides for versatile dosing regimens and routes of administration, including intra-articular, intra-neuronal (nerve block) and intradermal injection. This non-opioid-based CA8* mechanism-of-action addresses neuropathic, inflammatory, and nociceptive pain, which apply to a broad range of chronic pain indications, including osteoarthritis pain, diabetic and other forms of peripheral neuropathy, post-herpetic neuralgia, lower back pain, and cancer pain, as well as rare pain conditions such as erythromelalgia, an orphan drug disease. Using a nontoxic, disease-free, replication-defective HSV vector platform technology enables disease-free localized delivery to the peripheral somatosensory nervous system with an excellent safety profile. HSV vectors are known for their stability and prolonged gene-expression, providing an excellent basis for long-term treatment.

About Adolore BioTherapeutics, Inc.

Adolore BioTherapeutics, Inc., is focused on developing novel therapies for the treatment of chronic pain and other pain and nervous system conditions or disorders. Our best-in-class programs are long-acting, locally administered intracellular (non-genome-integrative) minigene-therapies that are opioid-free Disease Modifying Anti-Pain therapies (DMAPs) designed to treat many forms of chronic pain.

The Company's current CA8* intracellular minigene therapy programs are in preclinical development for treatment of patients suffering from erythromelalgia, a life-long heritable chronic pain condition representing an orphan drug disease with no approved therapy, and chronic pain due to knee osteoarthritis, affecting a large number of patients that are often treated with opioids due to the lack of good alternatives, thus contributing to the ongoing opioid crisis.

For more information, visit adolore.com.

Forward Looking Statements

To the extent this announcement contains information and statements that are not historical, they are considered forward-looking statements within the meaning of the federal securities laws. You can identify forward-looking statements by the use of the words "believe," "expect," "anticipate," "intend," "estimate," "project," "will," "should," "may," "plan," "intend," "assume" and other expressions which predict or indicate future events and trends and which do not relate to historical matters. You should not rely on forward-looking statements, because they involve known and unknown risks, uncertainties and other factors, some of which are beyond the control of the Company. These risks and uncertainties include, but are not limited to, those associated with drug development. These risks, uncertainties and other factors may cause the actual results, performance or achievements of the Company to be materially different from the anticipated future results, performance or achievements expressed or implied by the forward-looking statements.

Investor Relations Contact

Paul H. Barone, Esq.
Chief Business Officer

pbarone@adolore.com