Endogenex says its ReCET system’s catheter delivers nonthermal pulsed electric field energy to duodenal tissue, initiating the body’s natural process of cell regeneration. [Illustration courtesy of Endogenex]
“If we don’t do something more effective with type 2 diabetes, it will break the back of every healthcare system in the world,” Pugh said in a Medical Design & Outsourcing interview. “We own a piece of that puzzle. Certainly, it’s a big puzzle, but we think we’re sitting on top of something that could be a really important piece.”
Endogenex calls its system ReCET, which stands for Re-Cellularization via Electroporation Therapy. ReCET treats inflamed and dysfunctional tissue associated with type 2 diabetic duodenopathy, delivering nonthermal pulsed electric field (PEF) energy to mucosal and submucosal duodenal tissue to initiate cell regeneration.
“We’ve known for 30 years that if you bypass the duodenum in a type 2 diabetic, about half the time they’re not diabetic anymore within about two to three weeks,” Pugh said. “That wasn’t because of the weight loss. They were doing these procedures to deliver weight loss, but the results came far ahead of a weight loss curve. We know that if you had to refeed that duodenum — for nutritional deficits or other issues — if you had to redo that, these patients became diabetic again just about as quickly.”
As some devicemakers try duodenum sleeves or coating, Endogenex developed a PEF catheter to electroporate cells in the mucosal and submucosal layers of the duodenal wall. But it’s not an ablative process like the pulsed-field ablation used to scar heart tissue in atrial fibrillation patients.
“We target the phospholipid bilayer membrane, and through an apoptotic-like cell death cause those first two layers of cells to die off,” Pugh said. “We don’t damage underlying stroma matrix. We can be selective for that, so those cells repopulate very quickly. … We are resetting a population of cells, and what looks like restoring more normal cell signaling [and] affecting insulin resistance very heavily, predominantly hepatic insulin resistance. By going in and repopulating those populations from stem cell, we are changing functionality and restoring what we think is liver-gut-brain innervation.”
It’s a minimally invasive, outpatient endoscopy procedure, but probably not a one-time treatment.
“Diabetic duodenopathy is really what we’re trying to target here,” she said. “Because it’s an inflammatory process, we think you will likely need to repeat this procedure over time. We have followed a cohort of early patients for years now, and that’s a cohort of patients that came off of insulin with this procedure. We think the retreatment paradigm looks like something in terms of years, but we don’t really know what the far tail end of this therapy benefit is going to be yet.”
The ReCET system
While a patient is sedated, the ReCET system’s catheter travels down through the esophagus, stomach and pylorus to the duodenum.
“A lot of work went into the catheter,” Pugh said. “Unlike other structures in the body, the duodenum is a very motile organ. We’re dealing with an organ that’s trying to kick you out of it the whole time you’re there. Ultimately, we need to have good stasis and the capability to fixate with the organ and deliver these pulses in a controlled way.”
The catheter has a radiopaque end and a metallic canister that deploys a flexible circuit to delivery nanosecond energy pulses to the duodenum’s thin wall.
The Endogenex ReCET system’s catheter is designed with an expandable electronic circuit for delivering pulsed field energy to the duodenum’s wall. [Illustration courtesy of Endogenex]
The physician controls the therapy under direct visualization with the endoscope, and uses the scope’s suction and tiny holes in the energy circuit to optimize wall opposition for direct tissue contact while pulsing.
“We’re using outward force and pressure, a little bit of stretch-mediated therapy, and then we’re actually pulling down on the wall with that tiny catheter,” Pugh said. “It’s just a simple way to use the existing channel in a scope to optimize the capability of contact and therefore delivery of therapy.”
The catheter starts deploying energy just past the ampulla of Vater, moving segment by segment for consistent coverage. Endogenex designed the catheter to navigate in a way that would be familiar to gastroenterologists, with the capability to adjust the circuit’s size and orientation for any patient’s individual anatomy.
“The design of how we’re delivering that energy — that circuit down to the way we lay out the alignment of those bars, the spacing of those bars and the depth of that field — needs to be really controlled in an organ that gives you a fair amount of variability,” Pugh said. “There’s a lot of folds there.”
“Design of the product has really refined itself over time,” she continued. “We see dose-related response in this device segment like I haven’t seen in any of my time in med device, and I’ve been a lot of years in med device. We started with a controlled targeting of the mucosal layer alone, and then we moved our depth field to penetrate both mucosa and submucosa. And then we improved what we would call some stretch-mediated therapy and really optimized surface area. Every place along that curve that we’ve done that, we’ve seen an incremental bump in efficacy, not only in blood sugar improvement, but in weight loss and in things like lipid profiles. A really tight dose-related response curve tells us that those therapy refinements have been important.”
What’s next for Endogenex
Endogenex CEO Stacey Pugh [Photo courtesy of Endogenex]
“If we think about the most logical next steps, knowing that we’re modifying the disease in the way that we are — if we get the patient on the table for an hour, we get compliance in a different way than any of the other therapies you have for type 2 diabetes, either pills or injections — you don’t want to withhold a therapy to late-stage disease or end-stage disease,” Pugh said. “Moving up that severity curve to earlier in the disease process is an obvious thing for us.”
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Endogenex also sees potential applications elsewhere in the gastrointestinal tract.
“When I think about diabetic duodenopathy as a whole, or this condition within the duodenum, while we’re very focused on following the Yellow Brick Road of medical device and pharma to blood sugar level as an endpoint — because that’s the way that things have been brought to market, was to treat lowering blood sugar — we’re doing that,” Pugh said. “But we don’t for a minute believe that inflammatory process only negatively affects glycemic control. There will be a lot of clinical work for us to continue to expand how changing this gut-based immunity or immune dysregulation within the duodenum can change disease overall.”
Endogenex is working on next-generation tech including a “radically smaller” energy generator as the company continues enrollment in its pivotal trial for a premarket approval (PMA) submission to the FDA. Pugh said the company hopes to complete pivotal trial enrollment by mid-2026, follow patients for a year and launch in 2028.
The company’s biggest hurdle might be recruiting suitable patients for its trial as frenzied investors fund a host of potential “diabesity” treatments.
“There is not a more active investment space from the pharmaceutical and biotech side than the space that we’re in,” Pugh said. “Not only are we out there trying to find the right patient and do all the things you have to do just to be able to isolate treatment effect, which narrows your cohort of patients, but then we have 100 pharmaceutical trials of different compounds. None of them treat diabetic duodenopathy, but more and more potent compounds like the GLP-1 category. … I need to know [patients] didn’t start a GLP-1 or stop a GLP-1 in the last six months, because we know about the weight rebound and this glycemic rebound that comes from stopping a GLP-1. Those things don’t have anything to do with whether this is an appropriate patient population at the end of the day, but they have everything to do with our capability to meaningfully isolate the treatment effect of a sham control trial.”
“We’re well into the trial,” she continued. “I think we’ve demonstrated we are capable to do it. It just never comes as fast or as cheap as you want it to.”
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