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December 29, 2023Women’s Healthcare
December 29, 2023Bioxcel Therapeutics
Biopharmaceutical firm developing breakthrough therapies in brain and immuno-oncology using AI techniques., developing high-value therapies, lowering costs...
BioXcel Therapeutics, Inc. is a clinical-stage biopharmaceutical firm developing breakthrough therapies in brain and immuno-oncology using artificial intelligence (AI) techniques. They are committed to developing high-value therapies to improve patients’ lives by leveraging cutting-edge technology and research. BioXcel Therapeutics uses a proprietary AI platform to lower pharmaceutical development costs and shorten schedules while increasing the likelihood of success. To uncover novel therapeutic indices, they combine existing licensed medications and clinically assessed product candidates with big data and proprietary machine learning algorithms.
Development of Drugs Using AI
The neuroscience and immuno-oncology initiatives of BioXcel Therapeutics use an AI-based approach to drug development. BXCL501, an experimental, patented, orally dissolving thin film formulation of dexmedetomidine developed for the treatment of agitation and opioid withdrawal symptoms, is one of BioXcel’s two most advanced clinical research initiatives. BXCL701 is a systemic innate immunity activator that is orally given for the treatment of aggressive types of prostate cancer and advanced solid tumors that are resistant or therapy-naive to checkpoint inhibitors.
BXCL501 is a selective adrenergic drug with a sublingual or buccal mode of administration that is easy to use and has shown a quick beginning of action in clinical tests. BXCL501 is likewise intended to alleviate agitation without causing drowsiness or unarousable sleep. This application may help physicians and caregivers manage patients with agitation or withdrawal symptoms. The FDA has designated BXCL501 as a breakthrough therapy for agitation associated with dementia, as well as a fast-track designation for agitation associated with schizophrenia, bipolar disorder, and dementia. In early 2021, they published promising topline findings from the TRANQUILITY Phase 1b/2 study for the acute treatment of agitation related to dementia, including Alzheimer’s disease. (1)
BXCL701 is a systemic innate immunity stimulator accessible orally and has two modes of action. BXCL701, which targets Fibroblast Activation Protein, can inhibit dipeptidyl peptidase (DPP) 8/9 and impede immune evasion by bridging the innate and adaptive immune systems (FAP). It is being developed for the treatment of aggressive types of prostate cancer and advanced solid ‘hot’ tumors that are unresponsive to checkpoint inhibitors or are treatment-naive. Two clinical studies with BXCL701 are presently underway: BXCL701 in combination with KEYTRUDA® (pembrolizumab) is now being tested in a Phase 1b/2 study for castrate-resistant prostate cancer (CRPC), including the aggressive form t-NEPC (2)
BXCL701 Combined with Pembrolizumab Could Be Used as Treatment for Metastatic Castration-Resistant Prostate Cancer
BXCL701 in combination with pembrolizumab demonstrated promising results with anti-tumor activity to refractory metastatic castration-resistant prostate cancer (mCRPC) with adenocarcinoma phenotype.
In 2020, out of 91,930 new cases of prostate cancer, up to 20% developed CRPC within five years. mCRPC is resistant to monotherapy; thus, an effort to improve survival has been made by using dual drug therapy. BX701 functions by triggering inflammation, specifically, it induces IL- 18 and IL-1ß proliferation.
Synergistic use of BXCL701 and pembrolizumab increases the cytotoxic NK cells and macrophages in the tumor and decreases the immunosuppressive T-regs. (3)
BXCL501 Demonstrates Minimal Agitation Across in Patients with Bipolar Disorder
BXCL501 is a selective α2A adrenergic receptor agonist that bypasses the first-pass metabolism, providing a better bioavailability.
A cohort study was performed, and 380 subjects were enrolled, out of which 378 had a minimum of one dose of BXCL501. The most recurrent diagnoses were mania, mixed episodes, and depression. After only 20 minutes of BXCL501, significant improvement in agitation has been noted in both groups.
Results were encouraging, revealing that BXCL501 significantly reduced agitation, and it is being studied as a non-invasive treatment for acute agitation in bipolar disorder. (4)
Effect of BXCL501 for Treating Acute Agitation in Patients with Bipolar Disorder
Acute agitation presents frequently in patients with bipolar disorder, increasing the risk of injuries, prolonged hospitalizations, and higher economic burden.
The objective of the study was to establish if a single dose of BXCL501 was effective in reducing symptoms of acute agitation in patients with bipolar disorder. Researchers enrolled adults (18-75 y/o) diagnosed with DSM-5 bipolar I or II and clinically agitated at screening and baseline with PANSS Excited Component (PEC) total score ≥14 and baseline score of ≥4 on ≥1 PEC item. Patients were selected for a single dose of BXCL501 120 μg, BXCL501 180 μg, or placebo.
Results demonstrated a clinically significant effect 2 hours after administration, lasting for 8 hours in patients acutely agitated with bipolar disorder. (5)
Pharmacokinetics of Dexmedetomidine after a Single Sublingual Dose of BXCL501 in Patients with Agitation Associated with Schizophrenia
Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist used to treat agitation in patients with schizophrenia and bipolar disorder.
This study was designed as an ascending dose, placebo-controlled, double-blind study. 135 adult patients (18-65 y/o) with agitation associated with schizophrenia enlisted in the study. Individuals received single doses of the medication or placebo. Efficacy was evaluated by measuring changes from baseline in PEC score 2 hours postdose.
Results indicate BXCL501 dose- and exposure-dependent improvement in agitation in patients with agitation associated with schizophrenia. (6)