BTI’s two most advanced clinical development programs are BXCL501, an investigational, proprietary, orally dissolving, sublingual or buccal thin film formulation of dexmedetomidine designed for the treatment of agitation and substance abuse withdrawal symptoms, and BXCL701, an investigational, orally administered, systemic innate immunity activator for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment naïve to check point inhibitors.
BXCL501 is an investigational, proprietary, orally dissolving, sublingual or buccal thin film formulation of dexmedetomidine (Dex), a selective alpha-2a receptor agonist for the treatment of agitation and substance abuse withdrawal symptoms.
BXCL501 is our most advanced neuroscience clinical program, being developed initially for the acute treatment of agitation in patients with schizophrenia and bipolar disorders. A selective adrenergic agent with a sublingual or buccal route of administration, BXCL501 is designed to be easy to administer and has shown a rapid onset of action in clinical studies. It is designed to generate a calming effect without producing excessive sedation. We believe it is highly differentiated from antipsychotics currently used as standard of care, which produce unwanted symptoms such as tremors, neutropenia and extra-pyramidal motor effects. Managing patient agitation in neuropsychiatric and neurodegenerative disorders represents a significant challenge for physicians and caregivers, and we believe BXCL501 has the potential to address these challenges while providing an efficient treatment regimen for patients.
In July 2020, we announced positive topline results from the SERENITY I and II pivotal trials for the acute treatment of agitation in patients with schizophrenia and bipolar disorders. BXCL501 consistently showed statistical superiority over placebo for the primary, secondary, and all exploratory endpoints. Both patient populations responded quickly to BXCL501, demonstrating statistically significant and clinically meaningful improvement in agitation beginning as early as 20 minutes in patients with bipolar disorders at both dose levels (120 mcg and 180 mcg), and as early as 20 minutes in patients with schizophrenia for the 180 mcg dose level. In addition, the duration of response lasted for at least four hours after treatment. Based on the data from the two Phase 3 trials, we plan to submit the Company’s first NDA in Q1 2021.
In addition, we are continuing our development of BXCL501, exploring this candidate as a potential treatment for agitation across neuropsychiatric disorders. The Company is currently conducting the TRANQUILITY trial, a Phase 1b/2 trial of BXCL501 for the acute treatment of agitation associated with dementia, and the RELEASE trial, a Phase 1b/2 study of BXCL501 for the treatment of opioid withdrawal symptoms. BTI expects to initiate a Phase 2 trial in patients with agitation associated with dementia, including COVID-19 patients, within the next several months.
BXCL701 is an investigational orally-available systemic innate immunity activator with dual mechanisms of action. Designed to stimulate both the innate and acquired immune systems, BXCL701 has the potential to inhibit dipeptidyl peptidase (DPP) 8/9 and block immune evasion by targeting Fibroblast Activation Protein (FAP). BXCL701, is currently being developed for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment naïve to checkpoint inhibitors.
BXCL701 currently has two ongoing combination therapy clinical trials:
The Company is currently conducting a Phase 1b/2 trial of BXCL701 in combination with KEYTRUDA® (pembrolizumab) for advanced prostate cancer (tNEPC and CRPC). The Phase 1b safety assessment of BXCL701 indicated that a split dose totaling 0.6 mg per day is the recommended dose when used in combination with KEYTRUDA. BTI has entered into the Phase 2 efficacy portion of this trial, with an additional efficacy update planned for the near future.
The MD Anderson-led Phase 2 open-label basket trial was designed to evaluate the response rate of orally administered BXCL701, combined with KEYTRUDA, in two arms: Arm A is enrolling checkpoint naïve patients (where checkpoint therapy is indicated: “hot tumors”); and arm B is enrolling patients who have progressed following checkpoint therapy alone. The efficacy bar has already been met for both arms, allowing the trial to advance to completion.