Years ago, talabostat (BXCL701) failed during a Phase 3 clinical trial to evaluate the therapy for patients with pancreatic cancer. However, drug developer BioXcel Therapeutics (“BioXcel”) did not give up on the therapy. Rather, the company continued to work on and develop the treatment, intent on fulfilling an unmet need within this patient community.
According to Fierce Biotech, BioXcel, alongside Georgetown University researchers, recently discovered that talabostat could provide benefits for patients. In mice models of pancreatic cancer, treated with talabostat and immunotherapy, the combination treatment helped mitigate tumor growth and improve immune response. Interested in learning more? Take a look at the full research findings published in the Journal for ImmunoTherapy of Cancer.
As the name suggests, pancreatic cancer forms in the pancreas, an organ behind the lower stomach. Normally, the pancreas produces enzymes and hormones that play a role in digestion and blood sugar management. Exocrine pancreatic cancer, the most common form, begins in pancreatic duct cells. Alternately, pancreatic neuroendocrine tumors form in the hormone-producing cells. Risk factors include being obese, smoking, age (45+), and having a family history of pancreatic cancer.
Pancreatic cancer is often difficult to detect in early stages due to lack of symptoms. When symptoms appear, these include:
- Newly onset, or worsening, diabetes
- Appetite loss
- Unintended weight loss
- Jaundice (yellowing of the skin and eyes)
- Dark urine and pale stools
- Blood clots
- Upper abdominal pain that radiates to the back
- Bowel obstructions
So what exactly is talabostat? According to the National Library of Medicine, talabostat is:
“a small molecule with antineoplastic and hematopoiesis-stimulating activities. By cleaving N-terminal Xaa-Pro or Xaa-Ala residues, talabostat inhibits dipeptidyl peptidases, such as fibroblast activation protein (FAP), resulting in the stimulation of cytokine and chemokine production and specific T-cell immunity and T-cell dependent activity.”
Let’s break that down a little so it’s easier to understand. Antineoplastic means that the drug works to stop tumor development. Hematopoiesis-stimulating means that talabostat improves blood cell production. Additionally, the treatment inhibits dipeptidyl peptidase, a type of protein that can prompt tumor growth.
In prior studies, researchers suggested that talabostat could improve the efficacy of immunotherapy. Thus, researchers from Georgetown sought to explore whether this was true. To begin, researchers treated mice models of pancreatic cancer with talabostat. The researchers found that:
- Talabostat therapy helped improve T cell and natural killer (NK) cell levels. Both of these immune cells work to destroy cancer cells. Additionally, NK cells also create signaling molecules which prevent the tumor from growing.
- Alongside immunotherapy, talabostat developed an “immune memory” in 77% of treated mice. Basically, after researchers re-exposed the mice to the same cancer, the immune systems were prepared to stop or prevent tumor growth.
- Higher NK cell levels in patients with pancreatic cancer allowed for longer survival, other studies show.
In the future, both BioXcel and the researchers from Georgetown hope to continue evaluating talabostat and immunotherapy as potential therapeutic options for patients.