BTI’s two most advanced clinical development programs are BXCL501, an investigational, sublingual thin film formulation for the acute treatment of agitation resulting from neuropsychiatric disorders, and BXCL701, an investigational orally administered systemic innate immunity activator for the treatment of a rare form of prostate cancer and for treatment of pancreatic cancer in combination with other immuno-oncology agents.
BXCL501 is an investigational sublingual thin film formulation of dexmedetomidine (Dex), a selective alpha-2a receptor agonist for the treatment of acute agitation.
BXCL501 is our most advanced neuroscience clinical program, being developed initially for the treatment of acute agitation in patients with schizophrenia and bipolar disorders. A selective adrenergic agent with a sublingual 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 the potential 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.
The Phase 1b trial of intravenously dosed dexmedetomidine in schizophrenia patients demonstrated safety and established an optimal dose range for BXCL501. The Phase 1 pharmacokinetic (bioavailability) and safety study of BXCL501 yielded positive top-line data in 28 healthy volunteers.
The Phase 1b, randomized, double blind, placebo-controlled, multi-center, U.S. trial reported positive topline data in 90 schizophrenia patients. BXCL501 met its primary endpoint and demonstrated statistically significant and clinically meaningful rapid mean reduction in PEC (PANSS or the Positive and Negative Syndrome Scale, Excitatory Component) score at two hours compared to placebo following a single dose of 80 mcg (p=0.0152), 120 mcg (p=0.0003) and 180 mcg (p<0.0001). Results from secondary analyses showed statistically significant calming as measured by the ACES (Agitation-Calmness Evaluation Scale) at two hours compared to placebo following a single dose of 80 mcg (p=0.0156), 120 mcg (P=0.0005) and 180 mcg (P<0.0001). BXCL501 was well tolerated with no serious or severe adverse events across the entire dose range.
Phase 3 Pivotal trials are anticipated to enroll approximately 600 to 700 patients (300-350 each in schizophrenia and bipolar disorder) and are designed to measure reduction in PEC at two hours as the primary endpoint, as used in clinical trials of other approved agents. A data readout is expected in 1H 2020.
BXCL501 adaptive Phase 1b trial in agitated Alzheimer’s disease/dementia patients is expected to begin in Q4 2019. Development plans for the acute treatment of agitation with BXCL501 in hyperactive delirium and opioid withdrawal are underway.
BXCL701 is an investigational orally-available systemic innate immunity activator with dual mechanisms of action. It has shown single agent activity in melanoma and safety has been evaluated in more than 700 healthy subjects and cancer patients. Designed to stimulate both the innate and acquired immune systems, BXCL701 is designed to inhibit dipeptidyl peptidase (DPP) 8/9 and block immune evasion by targeting Fibroblast Activation Protein (FAP). BXCL701, is currently being developed for treatment of a rare form of prostate cancer and for pancreatic cancer in combination with other immuno-oncology agents.
BTI is currently enrolling patients in the U.S. in a clinical trial evaluating the double combination of BXCL701 and Keytruda® for treatment emergent Neuroendocrine Prostate Cancer (tNEPC). Multiple patients have been treated in the safety and escalation portion of the trial, which will be followed by a two-stage efficacy portion of the clinical program. A data read out is expected in 2H 2019.
A Clinical Trial Application (CTA) was accepted by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) for the double combination trial of BXCL701 and Keytruda® in tNEPC patients. BTI expects to activate clinical sites, subject to approval from local U.K. authorities. CTA authorization is the first step in BTI’s plan to expand clinical trials globally.
The FDA authorized the IND application for the triple combination of BXCL701, bempegaldesleukin (produced by Nektar Therapeutics, Inc., or Nektar) and BAVENCIO® (avelumab, Merck KGaA, Darmstadt, Germany and Pfizer) in pancreatic cancer. The safety escalation portion of the trial is ongoing and will be followed by a two-stage efficacy portion. A data read-out is expected in 1H 2020.
BTI is pursuing a clinical proof of mechanism study with BXCL701 in pancreatic cancer patients to characterize immune cell infiltration and activation and the circulating cytokines elicited in order to evaluate its mechanism of action.
BTI is continuing to explore additional indications for BXCL701 with synergistic combinations.