FrostBite-DMR - A New Drug-Free Approach for Treating Type 2 Diabetes

Type 2 diabetes mellitus (T2D) is increasing in incidence throughout the world with nearly 552 million
people who may be afflicted with this disease by 2030. There are now over 50 different drugs that can
be used to treat T2D but about half of patients do not respond well to these agents and their
hyperglycemic condition remains a life-threatening problem. Indeed, the first line drugs such as
Metformin, GLP-1 receptor agonists (e.g. Semaglutide), DPP-4 inhibitors, SGLT2 inhibitors and
others have documented side effects that include hypoglycemia, gastrointestinal side effects,
pancreatitis, pancreatic cancer, thyroid cancer, gallbladder issues, cardiovascular changes, acute
kidney injury, diabetic retinopathy, allergic reactions, increase in biliary disease, change in taste and
headaches. As an alternative to these drugs, the first in human report was published in 2016 showing
that duodenal mucosal resurfacing (DMR) of T2D patients could improve their hyperglycemic
conditions as well as several hepatic indices without having to use these front line drugs. This study
was initiated, in part, because of the well documented and surprising observation that bariatric
surgery also resulted in a similar benefit to T2D patients that was independent of consequential
weight loss. Since 2016 several clinical studies have been conducted on DMR and all showed benefit
to patients with T2D who weren’t responding to traditional medical treatments or who were non-
compliant with medications. While promising, DMR has been reported to have a high rate of technical
failure due to catheter malfunctioning suggesting that improvements in the technical-functional
aspects of current devices need to be addressed. Furthermore, one such DMR device that has shown
benefit in several clinical trials uses hydrothermic ablation (hot water at 80 to 90°C) to achieve DMR.
Like radiofrequency ablation, HiFU, microwave and other heat ablation technologies used to target
and ablate tumors and treat cardiac arrhythmias, the passive spread of heat can’t be easily controlled
and has shown to result in collateral tissue damage such as muscular segmental necrosis and serosa
bleeding with postoperative adverse events from DMR hydrothermic ablation reported to be an issue
with 64% of the cases. CPSI Biotech intends to capitalize on this emerging DMR market that is
currently in its infancy and develop an improved DMR thermal ablation probe that uses freezing
(cryoablation) rather than heat for duodenal resurfacing. The advantages of the proposed FrostBite-
DMR cryoballoon include (a) freezing is self-limiting in contrast to heat and presents less opportunity
for collateral damage to adjacent deeper duodenal tissue; (b) cryoablation has been shown to be
more effective, safer and have fewer complications than heat based ablation in numerous tissues
including cardiac, esophageal, renal, prostate and pancreatic among others; (c) CPSI’s PSN
cryoablation systems can generate and deliver ablative temperatures faster and colder than any other
known cryoablation systems currently on the market thus decreasing procedural time and, as such,
will offer improved versatility and safety compared to current technologies. The Specific Aims of this
project are the following: (SA1) Determine the thermal ablative dose of duodenum cells subjected to
cryoablation; (SA2) Develop FrostBite-DMR™, a flexible endoscope compatible cryoballoon, and
(SA3) Test the efficacy of FrostBite in ex vivo and in vivo models. The overall intent of the project is to
capitalize on the documented success of DMR published in the last few years as well as CPSI’s
expertise in developing improved cryoablation catheters so that an improved DMR ablation device
can be developed that is safer, more efficient, and can be better operator controlled leading to more
successful DMR for T2D patients who do not respond well to current T2D drug treatments.