Normal Function of Gastrin
- Gastrin is produced in the G-cells of the stomach.
- Gastrin acts on CCK-B receptors to produce the gastric acid needed for digestion.
- CCK-B receptors are normally located in the stomach, colon, and pancreas.
CCK-B Receptors are Overexpressed in some Cancers
- Gastrin is also secreted by these cancers to create an autocrine loop.
- Gastrin stimulates growth of these cancers.
- PAS blocks the trophic effects of gastrin and disrupts tumor growth.
- Growth promoting effect of gastrin peptides suggests gastrin system has broad carcinogenic significance.*
* Burkitt et. al. World J Gastroenterol 2009 January 7; 15(1): 1-16. “There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors.“
Gastrointestinal Cancers Present a Unique Challenge
- GI cancers as a group are the most common cancers in the U.S. (2019 prevalence below)
- Gastric ~100,000
- Pancreatic ~75,000
- Esophagus ~47,000
- Colorectal ~1.3 M
- Often diagnosed at an advanced stage
- Extremely poor prognosis
- Few effective treatment options for advanced patients
Polyclonal Antibody Stimulator (PAS) inhibits gastrin, minimizing cellular proliferation and tumorigenesis in GI cancers
Source: GI Alliance, seer.cancer.gov
- PAS is a peptide-conjugate that includes an epitope of human gastrin (G17) linked to carrier diphtheria toxoid.
- PAS activates B-cells and elicits specific and high-affinity anti-gastrin Abs, which prevent trophic activity of gastrin at the CCK-B receptor.
- PAS produces a G17 antibody response in 50-80 % of subjects.
- PAS is administered in humans as an intramuscular injection over a multi-week regimen.
The PAS vaccine was discovered at the University of Nottingham and developed into Phase 3 by Aphton. It was acquired Cancer Advances in 2008.
GMP material has been manufactured for 22 clinical trials, including two Phase 3 trials. Robust, cost efficient production.
PAS has previously been called G17DT and Gastrimmune.
Excellent safety and tolerability profile.
Cancer Advances exclusively owns PAS and is funding and managing all aspects of the PAS gastrin vaccine program.
PAS Clinical Program Overview
22 clinical studies have been completed in over 1,500 subjects, including 2 placebo-controlled Phase 3 studies
PAS has been actively investigated in three different indications:
6 pancreatic cancer studies, Phases 1-3
-Total exposure: n = 6545
Gastric cancer studies, Phases 1-2
-Total exposure: n = 234
5 colorectal cancer studies, Phases 1-2
-Total exposure: n = 368
Excellent safety and tolerability profile. Injection site irritation only notable AE. No adverse reactions or autoimmune effects were detected effecting the normal functions of gastrin.
Provides survival benefit in pancreatic and metastatic gastric cancer patients that show an immune response (≥65% of all treated patients)
Recent pre-clinical work by Georgetown University validates efficacy as a monotherapy and supports further exploration of PAS in combination with checkpoint inhibitors