Twenty-four years ago, then pediatric surgery fellow James Dunn, MD, PhD had an idea for a way to help children with short bowel syndrome (SBS), a devastating condition that makes normal eating impossible because there isn’t enough functional small intestine to absorb adequate nutrition.
“I was listening to a plastic surgeon present on a technique called distraction osteogenesis, which he was using to help pediatric patients with undersize jaws,” Dr. Dunn recalled. “By applying measured force, he was able to make the bones grow. I thought the technique might work for SBS and decided that, after my fellowship, I would study using mechanical solutions to stimulate intestinal growth.”
Earlier this year, Dr. Dunn finally got to see his concept become a clinical reality when Eclipse Regenesis, a startup Company-in-Residence (CIR) at Fogarty Innovation that he co-founded with FI board chair Tom Krummel, MD, and CEO Andre Bessette, successfully enrolled and treated its first adult SBS patient.
In the procedure, the Eclipse XL1 System, a small, spring-like device, is placed inside of the small intestine in a compressed state. As the device gradually expands, it exerts a controlled stretch force on the intestine tissue to stimulate the growth of new tissue. This newly created tissue looks and acts like normal healthy intestine tissue. After the XL1 has done its job, it is released and travels through the rest of the digestive tract and passes out of the patient.
“This was the first patient in our feasibility study, so our primary outcome is safety,” said Andre. “But while the device was in place, it appeared to safely stimulate the growth of new small intestine tissue.” Two months after treatment, it was confirmed that the XL1 had passed naturally out of the patient, as per the study protocol. Andre continued, “We are thrilled that we met all of our primary safety endpoints as well as our secondary outcomes including tissue lengthening and natural passing.”
SBS generally results from surgical removal of all or part of the small intestine due to disease, birth defects, or traumatic injury, and often leaves the patient reliant on intravenous feeding (total parental nutrition or TPN). This dramatically affects quality of life and carries a high risk of central line infections, metabolic imbalance, and liver failure. The only other option, a small bowel transplant, is a major surgical procedure with associated risks including the need for immunosuppression.
Placement of the Eclipse XL1 was performed by Joseph Forrester, MD, MSc, FAWM, FACS, an assistant professor of surgery in the Stanford Medicine Division of Acute Surgery, and a principal investigator on the study. Dr. Forrester noted that SBS often results from surgical procedures to repair trauma-related abdominal injuries, and these are extremely challenging problems for patients. “These patients often feel like they can’t go out into public because they are TPN dependent, which leads to frequent central line infections, and because they have these large wounds. I got involved in the study because if there’s a way to get a patient off TPN without a massive operation and all of its associated risks, that would be a gamechanger.”
He added, “Getting this device into a human and making sure that it is safe required an incredible team. Our clinical trials team in the Division of General Surgery really went above and beyond to help this patient get into the study and have the highest possible chance of success. Based on what we’ve seen so far, this is a very promising approach.”
The Long Road to Patient Care
Dr. Dunn hoped to bring his idea to pediatric patients years earlier. “I had completed 12 years of research on the concept and obtained a patent,” he related. “But I naively thought that the rest would just get done.” The reality is that translating a concept from the academic laboratory to clinical practice takes a tremendous amount of time and money. Many times great ideas at a university get stuck in bureaucracy and lack the resources to become an actual medical device.
However, when Dr. Dunn moved from UCLA to Stanford in 2016 to take a position as surgeon-in-chief at Lucile Packard Children’s Hospital, he met Tom Krummel, an experienced medtech innovator and then co-director of Stanford Biodesign. Meanwhile, Andre, an experienced medtech entrepreneur, had come across Dr. Dunn’s approach separately in his search for promising solutions to bring forward. Andre had worked with Dr. Krummel closely over the years and, once all the connections were made, the team was off and running.
Eclipse Regenesis raised seed funding in 2019 and two years later, the company joined Fogarty Innovation’s Company Accelerator Program (CAP). This focused program is designed to help early-stage companies develop a comprehensive approach to address their desired opportunity. At FI, the Eclipse team worked with lead mentor Craig Straley to develop their regulatory and clinical trial strategy, and hone other aspects of their business model. One key pivot requested by the FDA was that the company perform their initial studies in adult patients although the initial goal was to treat pediatric patients. Ultimately, the goal is for the System to treat both pediatric and adult patient populations.
An Impressive Timeline
Eclipse has made impressive progress reaching first-in-human in four years. Evidencing the acuity of the need, the company has been awarded extensive grant funding including a Stanford-Coulter Translational grant, Phase 1 and Phase 2 Small Business Innovation Research grants from the National Science Foundation, and Phase 1 and Phase II Fast Track Grants from the National Institutes of Health*. The team also won grants from the UCSF-Stanford Pediatric Device Consortium, and the CTIP Pediatric Device Consortium. Most recently, the company closed an inside Series A financing.
“While our progress is actually remarkable from a capital efficiency point of view, it feels like a long time to wait to see the first clinical outcome of a new technology,” said Andre. “But when I complain, Dr. Dunn reminds me that while it may be four years for me… it has been 24 years for him!”
Next, in addition to continuing the feasibility study, the team is working on evolving the device placement procedure from open to minimally invasive surgery. “Ultimately, the intent is for multiple devices to be placed sequentially until sufficient lengthening is achieved,” explained Andre.
“It was incredibly gratifying to see the device work exactly the way we expected,” commented Dr. Dunn. “Now we have to keep marching towards the goal of being able to use this safely and effectively to help children with SBS. Eating is such a big part of being alive.
*Research reported in this publication was supported by the National Institute Of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under Award Number R44DK127658. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.