Business description of AXSOME-THERAPEUTICS-INC

expectations for increases or decreases in expenses;

expectations for the clinical and preclinical development, manufacturing, regulatory approval, and commercialization of our pharmaceutical product candidates or any other products that we may acquire or in-license;

estimates of the sufficiency of our existing capital resources combined with future anticipated cash flows to finance our operating requirements;

expectations for incurring capital expenditures to expand our research and development and manufacturing capabilities;

expectations for generating revenue or becoming profitable on a sustained basis;

expectations or ability to enter into marketing and other partnership agreements;

expectations or ability to enter into product acquisition and in-licensing transactions;

expectations or ability to build our own commercial infrastructure to manufacture, market and sell our product candidates;

expected losses;

ability to obtain and maintain intellectual property protection for our product candidates;

acceptance of our products by doctors, patients, or payors;

stock price and its volatility;

ability to attract and retain key personnel;

the performance of third-party manufacturers;

expectations for future capital requirements; and

our ability to successfully implement our strategy.

PART I

Unless the context requires otherwise, references in this report to “Axsome,” “Company,” “we,” “us” and “our” and similar designations refer to Axsome Therapeutics, Inc. and our subsidiaries.

ITEM 1. BUSINESS.

OVERVIEW

We are a clinical stage biopharmaceutical company developing novel therapies for the management of central nervous system, or CNS, disorders for which there are limited treatment options. By focusing on this therapeutic area, we are addressing significant and growing markets where current treatment options are limited or inadequate. Our product candidate portfolio includes two late‑stage candidates, AXS‑05 and AXS‑02, which we are developing for multiple indications. We have initiated a Phase 3 trial with AXS-05 in treatment resistant depression, or TRD, which we refer to as the STRIDE-1 study, and plan to initiate a Phase 2/3 trial in agitation in patients with Alzheimer’s disease, or AD. We have also initiated a Phase 3 trial with AXS‑02 in complex regional pain syndrome, or CRPS, which we refer to as the CREATE-1 study, and a Phase 3 trial with AXS-02 in knee osteoarthritis, or OA, associated with bone marrow lesions, or BMLs, pursuant to a Special Protocol Assessment, or SPA, which we refer to as the COAST-1 study. We also plan to initiate a Phase 3 trial with AXS-02 in chronic low back pain, or CLBP, associated with Modic changes, or MCs. We aim to become a fully integrated biopharmaceutical company that develops and commercializes differentiated therapies that expand the treatment options available to caregivers and improve the lives of patients living with CNS disorders.

Our first product candidate, AXS‑05, is an innovative fixed‑dose combination of dextromethorphan, or DM, and bupropion. We are developing AXS‑05 initially for the treatment of the following two conditions: TRD and agitation in patients with AD. DM is active at multiple CNS receptors but is rapidly and extensively metabolized in humans. As a result, it is difficult to attain potential therapeutic plasma levels of DM when it is dosed as a single agent. AXS‑05 uses bupropion as a novel drug delivery method to inhibit DM metabolism and increase its bioavailability. We have demonstrated in three Phase 1 trials that DM plasma levels are substantially increased into a potentially therapeutic range with the co‑administration of bupropion. Bupropion is itself active at distinct CNS receptors providing the potential for an additive or synergistic effect. We intend to seek FDA approval for AXS‑05 utilizing the 505(b)(2) regulatory development pathway.

We initiated a Phase 3 trial with AXS‑05 in TRD, which we refer to as the STRIDE-1 study, in March 2016. Top-line results from this clinical trial are anticipated in the first quarter of 2018. Currently only one product, Symbyax, a combination of olanzapine and fluoxetine, which is marketed by Eli Lilly and Company, is approved in the United States for the treatment of TRD. DM’s mechanisms of action encompass those of several antidepressant drug classes, and bupropion is a well‑established antidepressant. DM administration has resulted in dose‑dependent antidepressant‑like effects in two widely used preclinical models of antidepressant effect. Furthermore, administration of DM with quinidine, which serves as an inhibitor of metabolism of DM, resulted in a statistically significant reduction in depressive symptoms in patients with pseudobulbar affect, which is a disorder characterized by involuntary, sudden, and frequent episodes of laughing or crying, as shown in a third‑party study. The term statistically significant denotes an experimental result, such as one derived from a clinical or non‑clinical trial, that is unlikely to have occurred by chance. The plasma concentrations of DM achieved with AXS‑05 in our Phase 1 trials are in the range of those associated with the DM and quinidine dose that resulted in a reduction in depressive symptoms in patients with pseudobulbar affect, based on data published by the FDA. AXS-05 has been granted FDA Fast Track designation for TRD. We estimate that as many as 3 million individuals in the United States suffer from TRD.

Business description of AXSOME-THERAPEUTICS-INC from last 10-k form