Axsome Pain and Primary Care (Axsome PPC)

Axsome Pain and Primary Care (Axsome PPC) is a new business unit developed to house, manage, develop and enhance the value of Axsome’s non-CNS assets. The assets in Axsome PPC include three Phase 3-stage product candidates. Two of the product candidates (AXS-06 and AXS-02) are being developed directly by Axsome, and one of the candidates (neridronate) is covered by Axsome’s intellectual property portfolio. These product candidates are being developed for five different indications including the signs and symptoms of osteoarthritis and rheumatoid arthritis, osteoporosis, the pain of knee osteoarthritis, chronic low back pain, and complex regional pain syndrome.

AXS-02

AXS-02 (disodium zoledronate tetrahydrate), is a potentially first in class, oral, targeted, non opioid therapeutic for chronic pain. We are initially developing AXS-02 for the treatment of pain in the following conditions: knee osteoarthritis (OA) associated with bone marrow lesions (BMLs) and chronic low back pain (CLBP) associated with Modic changes (MCs). AXS-02 has been granted Fast Track designation by the FDA for the treatment of pain associated with the treatment of knee OA associated with BMLs. AXS-02 has also been granted Orphan Drug Designation by the FDA and Orphan Medicinal Product Designation by the EMA. AXS-02 is an investigational product candidate not approved by the FDA.

A New Therapeutic Approach

How It Works

The active molecule in AXS‑02 is a potent inhibitor of the bone‑resorbing cells called osteoclasts. Osteoclasts break down bone by secreting protons or acid. As acid is known to excite pain receptors, the effects of AXS-02 on osteoclasts may reduce pain by suppressing localized over-production of acid in bone. AXS-02 may also inhibit the production of pro‑inflammatory cytokines which have been shown to contribute to pain.

Clinical

AXS-02 is also in a Phase 3 trial in knee OA associated with BMLs. This trial has received a Special Protocol Assessment (SPA) from the FDA. AXS-02 has been granted Fast Track by the FDA for the treatment of knee OA associated with BMLs.

An Independent Data Monitoring Committee (IDMC) conducted an interim analysis of the Phase 3 COAST-1 trial of AXS-02 in knee OA associated with BMLs in January 2018 and recommended that the study continue to full enrollment.

An additional Phase 3 trial with AXS-02 is planned in CLBP associated with MCs.

Product Pipeline

Indications

Knee Osteoarthritis (OA)

Knee OA is a disorder characterized by bone changes around the knee joint, progressive loss of joint cartilage, joint space narrowing, and eventual total joint failure. Knee OA results in knee pain, significant physical disability, and reduced quality of life. Some patients with knee OA exhibit bone marrow lesions (BMLs). BMLs appear as areas of increased signal intensity on MRI of the knee, and are associated with knee pain, disease severity and disease progression. Results of epidemiological studies suggest that there are approximately 12 million patients in the United States, 50 years of age and older, with symptomatic knee OA, of whom an estimated approximately 7 million have BMLs.

More about knee OA

Chronic Low Back Pain (CLBP) Associated with Modic Changes (MCs)

CLBP is defined as persistent or fluctuating low back pain lasting at least three months. MCs are vertebral bone marrow changes that are visible on MRI of the spine, and that represent regions of increased bone turnover and pro‑inflammatory mediators. Results of epidemiological studies suggest that there are approximately 121 million adults in the United States with low back pain in a given year. Approximately 9 million of these sufferers are estimated to have CLBP, of whom we estimate approximately 1.6 million have type 1 MCs.

More about CLBP
AXS-06

AXS-06 is an oral, non-opioid, fixed-dose combination of MoSEIC™ meloxicam and esomeprazole under development for the treatment of chronic pain. AXS-06 utilizes Axsome’s proprietary MoSEIC™ (Molecular Solubility Enhanced Inclusion Complex) technology to substantially increase the solubility and speed the absorption of meloxicam while maintaining durability of action. Meloxicam is a long-acting nonsteroidal anti-inflammatory drug (NSAID) with COX-2 preferential inhibition. Esomeprazole is a proton pump inhibitor that lowers stomach acidity which has been shown to reduce the occurrence of NSAID-induced gastrointestinal ulcers. AXS-06 is an investigational drug product not approved by the FDA.

An Improved Therapeutic Approach

How It Works

The components of AXS-06, MoSEIC™ meloxicam and rizatriptan, are combined for a potentially synergistic effect with enhanced efficacy over currently available therapies in the treatment of migraine. Meloxicam is an NSAID that provides potent pain relief with a long duration of action. However, standard meloxicam has an extended time to maximum plasma concentration (Tmax). AXS-06 utilizes Axsome’s proprietary MoSEIC™ technology to achieve rapid peak plasma levels of meloxicam after oral administration without compromising its long half-life. Rizatriptan is currently approved as a single agent for the acute treatment of migraine and targets different migraine-inducing CNS receptor systems than meloxicam

Clinical

Based on Pre-Investigational New Drug Application (Pre-IND) guidance from the U.S Food and Drug Administration (FDA), AXS-06 is planned for a Phase 3 trial.

Product Pipeline

Indications

Osteoarthritis and Rheumatoid Arthritis

Osteoporosis is a degenerative bone condition characterized by an imbalance in bone resorption and formation resulting in porous and brittle bones that are prone to fracture.

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