AltrixBio Creates the Benefits of Surgery in a Pill

As chief of General and GI surgery at Brigham and Women’s Hospital in Boston and a bariatric surgeon, Ali Tavakkoli was intrigued by the observation that patients having gastric bypass surgery were coming off their diabetes medications while still in the hospital and before they'd lost any weight. He wondered if there was a way to develop an oral daily therapy that would mimic the benefits of surgery, but without the risks.  This gave birth to the idea of “surgery in a pill,” which has been the driving force behind AltrixBio’s research since. 

He teamed up with Jeff Karp, a serial entrepreneur who runs the Karp lab at the Brigham, and they began looking to find a drug for this effect, eventually spinning a new company, AltrixBio, out of the Brigham in 2019 after their early studies showed that a new compound that they had generated, called LuCI or AJN 003, could mimic the benefits of gastric bypass surgery in rodent models. 

Gastric bypass surgery is used to help obese patients get to a healthy metabolic state by bypassing the lower stomach and proximal intestine to move metabolism of food further down the GI tract, leading to changes in neurohormonal signaling, which in turn leads to a rapid improvement in glucose control and diabetes. That’s important because 70% of people who are overweight or obese also have type 2 diabetes. The beneficial impact of gastric bypass surgery has now been shown in multiple randomized studies and long term studies have also shown that in comparing gastric bypass surgery to medical therapy over a 12-year follow-up, surgery leads to much higher rates of diabetes remission and improvement,  with patients that were on medications for diabetes, including insulin, coming off their medications. 

“The mechanism of action, validated in numerous clinical studies of patients for bariatric surgery, has found bariatric surgery to be the gold standard for treating obesity and for type 2 diabetes, but it’s very invasive and only 1% to 2% of all patients who qualify for bariatric surgery actually have the surgery,” says Nancy Briefs, co-founder and CEO of AltrixBio. “The vision of our company is, can we deliver a daily oral therapy that replicates the benefits of surgery and that we've demonstrated in animals, an approach we've trademarked as Surgery in a Pill.”

AltrixBio’s LuCI is a new patented formulation of a very well-known and safe drug called sucralfate. Sucralfate is an oral solution or tablet that has been prescribed by primary care physicians for more than 38 years for use in the stomach and intestine for irritated ulcers, which adheres to that area to protect it so that it can heal. 

“What's novel about our work, is that we have changed the formulation of sucralfate, a drug that in a pH dependent fashion binds to ulcerated intestinal mucosa, to a new compound that in a pH independent fashion binds to healthy intestinal mucosa,” Briefs explains. “It thus creates a luminal barrier that prevents food contact with proximal intestinal mucosa. The idea is that patients take LuCI before a meal once or twice a day.  LuCI then forms a paste that is delivered in the stomach and moves through the proximal small intestine, creating a temporary coating that replicates the effect of gastric bypass. And it means that when patients eat, the stomach and proximal intestine is not exposed to food content thanks to the coating, and now moved out further in the intestine where nutrient absorption is altered. We have shown in chronically obese animals that once daily LuCI treatment  leads to improved glucose levels and reduced weight.”

LuCI is in preclinical development, with two published studies demonstrating both acute and chronic results. The company has developed a scalable model for manufacturing and had a successful pre-IND meeting with the U.S. Food and Drug Administration. The company can also tap an expedited regulatory pathway because LuCI has 38 years of safety behind it.  

“The Agency actually suggested to us that in phase 1 studies we do patients that have type 2 diabetes and are either overweight or obese,” Briefs says. “And this is very exciting for us because it means that instead of a traditional phase 1 dosing in healthy patients, we can expedite our time to market.”

The company has a synopsis of a phase 1 dosing study prepared with selected sites in Australia to run the study.  Briefs says that given its regulatory path and safety, LuCI can move to the clinic more quickly given that the site they have chosen is an experienced site that has led a number of studies in cardiometabolic disease, particularly around the bariatric mechanism. 

“We're not the only company in this space. What distinguishes us from both the mechanical devices as well as the polymer approaches to do the same thing is that we actually are the closest to mimicking bypass surgery and that we deliver a coating to the stomach as well as the proximal intestine,” says Briefs. “By delivering to the stomach, unlike the other approaches, we have a gastric effect, actually suppressing the appetite stimulating hormones, both ghrelin and leptin, as well as having the proximal gut effect. We see an increase in the incretin hormones, both GLP-1 and GIP, and we see a very strong insulin sensitization.” 

The company’s development plans include looking to either partner LuCI or out-license it to a company that is in the cardiometabolic space in order to move into the clinic. AltrixBio is also looking to raise a series A of approximately $15 million, but it’s open to all three approaches, as it advances it’s goal to see LuCI being used in patients, notes Briefs.

It is with that idea that AltrixBio joined Bioneex’ drug marketplace platform. “We felt that it was a very interesting platform because it has a combination of both investors as well as pharma and biotech companies,” Briefs said. “We joined the platform so that we could get exposure for LuCI AJN OO3, and possibly find a good partner or collaborator here.”

AltrixBio also believes LuCI fits with the current GLP-1s and GIP (G) drugs that have had a phenomenal uptake and impressive clinical results, especially for patients that could not tolerate the GLP-1s or the GIPs as they are today. Briefs says a recently published study found that 50% of patients who start on GLP-1 drugs come off the drugs in the first year. Another recent study in JAMA showed that after two years, only 15% of patients stay on the drugs. 

“We think that we could be a great opportunity for those patients who cannot remain on the drug because we could be a rescue for weight gain,” Briefs says. “We know that when people come off of those drugs, they lose the glycemic control and they regain the weight. So LuCI could possibly be used there as a rescue for weight regain or possibly be used in combination with the G drugs and maybe even be synergistic to some of their efforts. We don't think of LuCI as a direct competitor to the G drugs, but we like to think of it as a potential best-in-class in oral daily drugs that could be used in the market.”

AltrixBio has plans for LuCI not just as a “one product” deal but as a platform because in manufacturing it is able to adjust the viscosity of LuCI for different dwell times. While AJN 003 meets the target product profile for diabetes, the company may find tweaking the profile may work for something different such as NASH or MASH or obesity. The company has demonstrated in preclinical animal models that LuCI has the potential to also be a carrier for other drugs delivered to the stomach such as peptides. 

“We like to think of LuCI as a very broad platform and our intellectual property, which has issued in the U.S. and Europe, provides for a wide range of potential indications,” says Briefs.