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Colleen Cutcliffe, CEO of Pendulum Therapeutics, sat down with Onyx for a feature-length interview.
From an investor's perspective, what makes Pendulum an attractive option?
Our first investors were the Mayo Clinic, who believed the microbiome was a new frontier in health — a belief I share. At our core, we're a biotech company, but we have the flexibility to create pharmaceutical drugs, consumer products, and more. We put our efforts into creating products that have the efficacy of drugs and the safety of probiotics.
So the next generation health company has to be able to keep that promise of safety alongside efficacy. And really where I think health is headed is there's no way to realize the promise of preventative medicine if you operate within the realms of how our drugs are developed here in the U.S. because there's this crazy catch 22, which is that you can only be called a drug and get reimbursement if you are solving a disease (that you’ve already been diagnosed with), that means that you're never preventing anything.
To truly realize preventative medicine, we can't operate solely within the traditional drug development framework, which focuses on treating diseases after they occur. By creating effective, safe, natural products, we can help people before they get sick.
Could you tell us about your partnership with a certain Hollywood star, and how that came about?
Sure. Many people don't know that Halle Berry has diabetes. She tried our product and saw her A1C go down. She asked to meet with us to find out, like: I've never heard of this company — what do you guys do? So I met her to explain how the product works a little bit more and what we're doing, and we hit it off. I mean, we're both really interested in helping people improve their health. We both have kids around the same age.
She invested in the company and offered to help build our brand.
She candidly said, "No offense, but you guys are doing a pretty terrible job at that." I agreed and said no offense taken! She's been instrumental in increasing our brand awareness, sharing her personal story, and explaining how our products have helped her.
So that was really the beginnings of the relationship where she said, you've created a product that changed my life. “How can I be helpful?”
And what’s your own background?
I have a Ph.D. in biochemistry and molecular biology from Johns Hopkins. After a postdoc at Northwestern, I worked in a pharma company developing drugs for Parkinson's disease — really as a scientist. Then I joined a startup called Pacific Biosciences, or PacBio as most people now know it, where I led the biology department. We went through rapid growth and eventually went public.
After that, I started Pendulum with two co-founders from PacBio — Jim, a biostatistician, and John, a biophysicist. We're all deeply technical. Around that time, about 11 or 12 years ago, the microbiome was primarily an academic endeavor. We believed we had the technical capabilities to use sequencing and biochemical assays to create metabolic maps of the microbiome and then develop interventions based on that.
On a personal note, my first daughter was born almost two months prematurely. She spent a month in intensive care, hooked up to machines and on lots of antibiotics. She was so fragile, just about four pounds.
Around that time, a paper by Marty Blaser from NYU showed that infants on multiple antibiotics were more prone to obesity and type 2 diabetes later in life. The Mayo Clinic replicated that study, showing that kids under two on lots of antibiotics were more prone not only to obesity and diabetes but also to allergies, asthma, celiac disease, and ADHD.
It was a pivotal moment. We had the technical knowledge to create products in the microbiome space that could help millions, including my own daughter. So, we started with metabolic syndrome, partly because of all that underlying data but also, quite selfishly, because I wanted to help my kid have a better future.
Could you give us an overview of the products Pendulum offers and the vision behind them?
We spent the first eight years in product development mode. We were creating metabolic maps of the microbiome, focusing on metabolic syndrome, with type 2 diabetes being the most extreme case. Our thought was, if we could move the needle on diabetes metrics, we'd be onto something significant.
Our flagship product is Pendulum Glucose Control. About ten years ago, we knew we were targeting the GLP-1 pathway. Our first Chief Medical Officer, Orville Kolterman, was previously the CMO at Amylin Pharmaceuticals, which introduced the first three GLP-1 drugs. He was retired, but I flew down to San Diego to convince him to join us.
I told him, "You've already made your mark in the GLP-1 drug world. We're targeting the same pathway but through the microbiome — the next phase of health. Don't you want to be part of that?" He joined us and helped design our preclinical and clinical trials.
After extensive work, we showed in a double-blinded, placebo-controlled, randomized trial that we could lower A1C by 0.6% and reduce blood glucose spikes by 33% in people with type 2 diabetes. Most of these individuals were already on metformin, so our product was an additive benefit. This was published in the BMJ. At that point, we had a decision: go down the drug path or the consumer health path. We chose the latter.
We then launched Metabolic Daily, the same formulation at a lower dose, allowing us to reduce the price. It's designed for anyone looking to boost their sugar metabolism but who is not yet at the clinical stage of type 2 diabetes.
This year, we introduced the GLP-1 probiotic, a subset of strains from Pendulum Glucose Control specifically designed to increase GLP-1. There are two strains known to directly stimulate GLP-1: Akkermansia muciniphila and Clostridium butyricum. We added a third strain that functions upstream of these two.
In traditional drug discovery, there's the whole FDA approval process. How did Pendulum navigate this?
We brought Peter Hutt onto our board early on. He's the former General Counsel of the FDA and was instrumental in creating the medical food category.
As a medical food, you don't need pre-FDA approval to bring products to market. You can run clinical trials just like you would for a drug but at a fraction of the cost.
You must be prepared to back up any claims if questioned. And, indeed, three months after launching Pendulum Glucose Control, the FDA knocked on our door. They said, "You can't say 'type 2 diabetes' for a supplement." We responded, "We're not a supplement; we're a medical food."
We underwent a three-month review, providing all our clinical data, including our BMJ publication. In the end, they agreed we had sufficient evidence to make our claims. That positioned us as the world's first and only microbiome intervention for people with type 2 diabetes under the medical food category.
Do you face skepticism for not following the traditional drug development path?
Only about a thousand times a day! Coming from traditional medicine and pharma, the decision to take this path was mission-driven, but it does impact credibility. That's why it's crucial that institutions like the Mayo Clinic are our investors, that we're three Ph.D. scientists who started this company, that we have endorsements from people like Peter Attia, and that we've published in the BMJ.
We're constantly fighting an uphill battle to prove our legitimacy. Since the FDA doesn't approve anything that's not a drug, we can't get that stamp without becoming a drug.
Can you explain what your pills contain and how the bacteria work?
Our capsules contain a combination of five probiotic strains and a prebiotic that feeds them. These strains work together to stimulate GLP-1 production and modulate the gut lining. To reach the gut microbiome in the distal colon, the capsules are enteric-coated and time-delayed to survive stomach acid and transit through the intestines. These strains are strict anaerobes, so we had to develop an end-to-end manufacturing process that excludes oxygen entirely.
From a patient's perspective, say someone with general gut issues or IBS who takes your supplement, what changes could they expect?
When you improve digestion, GI improvements often follow. But our primary promise is managing blood sugar spikes and crashes.
I don't have diabetes or prediabetes, but as I'm aging, I noticed spikes and crashes in my blood sugar. Wearing a continuous glucose monitor, I saw that these were minimized when I was on our product. For me, that translated into stronger workouts.
So, people can expect hard benefits like reduced blood glucose spikes, lower fasting blood glucose levels, and decreased A1C. Additionally, there are softer benefits: sustained energy, no post-lunch brain fog, better sleep. People often notice these improvements and realize their overall metabolic health is better.
Clinical trials are fundamental to our credibility, especially with healthcare practitioners who always want more data. We're running about ten different clinical trials to understand how our strains affect both healthy and diseased populations — looking at prediabetes, obesity, potential preventative applications, even considering teenage obesity and diabetes.
We've raised over $150 million, with most of it invested in research, clinical trials, and manufacturing. As we build foundational data, we're also heavily investing in marketing — which is expensive.
We have several clinical trials underway — we started some last year that should conclude in 2025, and we're incredibly excited about them. Beyond that, our primary goal is to continue building brand awareness and credibility. We're in a world where trust is hard-earned, so we’re proving the science just works.
