NBJ Award 2023: Science and Innovation

This article originally appeared in the Nutrition Business Journal's Awards Issue.

Long before Ozempic rocked the multibillion-dollar weight-loss industry, becoming the worst-kept secret that Hollywood stars were definitely not using to drop alarming amounts of weight, and long before Goldman Sachs predicted GLP-1 receptor agonists could improve Americans’ health outcomes enough to boost the U.S. economy by $1 trillion, the New Zealand government set out to find a natural solution for appetite control.

In 2009, Plant Food and Research, a New Zealand government agency tasked with researching nutraceutical products and clinically validating lab-based results, received a $15 million grant from New Zealand’s Ministry of Business, Innovation and Employment to develop a plant-based appetite suppressant for weight management. Nine years later, following rigorous research and three clinical trials, Calocurb, a gut-targeted nutraceutical that triggers the body to release appetite-suppressing hormones, was launched in New Zealand and the United States.

Plant Food and Research partnered with Calocurb to commercially develop and trademark Amarasate, a bitter extract from a rare New Zealand-grown hops flower that acts as a potent natural appetite suppressant. Amarasate works by stimulating gastric taste buds (receptors) to release natural gastric peptides CCK, PYY and GLP-1 (perhaps now the most recognized peptide in the Western world), which send a signal to stop eating from the stomach to the brain (a process Calocurb has trademarked as “the bitter brake”). Through a series of human clinical trials, Amarasate has been proven to reduce caloric intake an average of 18%, reduce overall hunger 30% and reduce overall cravings 40%.

Related:NBJ Summit offers insights into women’s health, great networking opportunities

“Calocurb’s number one value is that everything we do and say must be science-led—and because we are owned by the New Zealand government, it all has to be correct,” says Calocurb CEO Sarah Kennedy. “Science is expensive and takes years, so we are incredibly lucky that nearly all our primary research is done by the New Zealand government. I just don’t know a commercial company, unless it’s very, very large, that could spend the amount of time and money that Plant Food and Research has spent to research and develop this.”

That commitment to real science, backed by clinical studies, is the reason NBJ is recognizing Calocurb with the 2024 NBJ Award for Science and Innovation.

A New Zealand government agency was charged in 2009 with developing a plant-based appetite suppressant for weight management. Calocurb launched nine years later. Picture is the parliament building in Wellington, New Zealand. Credit: Canva

From concept to clinical application

The path to Amarasate’s discovery started with the Plant Food and Research team’s simple observation that plants are natural appetite suppressants. “Think about an apple tree—the apple is juicy and delicious, so you eat it, but the leaves and the seeds are not so tasty, so you’ll eat the apple but not the leaves and the seeds,” says Edward Walker, the Plant Food and Research scientist tasked with investigating how bitterness in the gut triggers appetite-suppressing gut hormones.

Related:NBJ Awards 2023 sharpen the focus on good works and big successes

Humans have been using bitter compounds to both stimulate and suppress appetite for centuries, Walker says, and his team realized that if bitterness could do both, the mechanism of action was probably not on the tongue. Through a hospital study of gut biopsies from 28 volunteers, the researchers discovered about 25 bitter taste receptors throughout the gut. “That was sort of a tick box for us,” Walker says. “Once we’d found that, then we said, OK, next question is, can we make this work with cells—can we activate this in the lab?”

A lab screening of 1,000 different plant extracts and compounds found that all but four did nothing to suppress appetite. The body is naturally resistant to releasing CCK, PYY and GLP-1, Walker says, because it would be detrimental if these peptides were triggered every time a bitter plant was ingested. “If mild bitterness worked, then every time someone had a cup of coffee, they’d suddenly feel full, right? So, what we found was that it had to be very potent to work.”

Of the 1,000 plants tested, only four were bitter enough to produce results, and only one—a specific cultivar of New Zealand-grown hops—was both stable enough and had a good safety profile. Plant Food and Research had already validated the hops extract, so there was plenty of data showing the plant would remain stable and wouldn’t vary from season to season.

“I’ve been really lucky as a scientist to be able to do research all the way from the basic concept through to clinical applications,” Walker says. “You don’t get a chance to do that a lot.”

In the three human clinical trials that have been conducted on Amarasate, it effectively suppressed appetite and reduced the amount of food study participants ate. In 2019, Walker published a randomized, double-blind crossover treatment study in Nutrients showing that Amarasate regulated participants’ appetite during a 16- to 24-hour water-only fast and reduced hunger and increased fullness during the fast’s late stages.

Calocurb just got ethics approval to conduct its fourth human clinical trial on 150 men and women measuring a number of biomarkers, including weight loss. “That’s costing us $2 million,” Kennedy says. “We’ll start in the first quarter of next year.”

Making inroads in the U.S.

Plant Food and Research recruited Kennedy, who had a track record of growing and managing health and wellness companies, to bring Amarasate to the consumer market in 2017. It was an offer she couldn’t refuse.

“A lot of things came into play for me,” Kennedy says. “There was this incredible science and an opportunity to be in a category which is just so large but has a lot of quackery in it.”

Kennedy raised money, built a team and launched Calocurb as a direct-to-consumer product in 2018—three years before the FDA approved Wegovy as the first GLP-1 agonist to be used for chronic weight management and two years before New Zealand’s strict border management in response to the COVID effectively isolated the country and its businesses from the rest of the world. The U.S. market remained out of reach during the pandemic, but as New Zealand lifted restrictions in 2022, Calocurb raised more money, partnered with Lonza in South Carolina to handle manufacturing, and renewed marketing efforts in the U.S. in early 2023.

Calocurb is just starting to make inroads into the practitioner channel in the U.S. When Walker presented at the Obesity Medicine Association conference in New York last April, Kennedy says, “We were just completely and utterly overwhelmed by the response. They love the science.”

Calocurb is appealing to a range of practitioners, from endocrinologists to naturopaths, who are looking for alternatives to Wegovy and Ozempic for patients who don’t fit the criteria to take them, can’t tolerate the side effects or can’t afford them. It can also be used to help patients titrate off those drugs and replace them as a more sustainable long-term solution. Calocurb can be taken alongside the pharmaceuticals as patients wean off them because it stimulates endogenous release of GLP-1 agonists, while the injections are exogenous.

In February, author and biohacking expert Ben Greenfield wrote in his newsletter that Calocurb “seems to really crush carb cravings and acts very similar to Ozempic, without the side effects.” In May, Dr. Ronald Hoffman, a popular complementary medicine podcaster, endorsed Calocurb. “In my 40-year history in medicine, I’ve never endorsed a weight-loss product because most don’t deliver—until now,” Hoffman wrote on his “Intelligent Medicine” site. “The science behind Calocurb and its active ingredient, Amarasate, is so compelling that I can support it as a plausible alternative for curbing appetite and enhancing satiety to help you shed pounds.”

Yet even with all of this science and influencer love, Calocurb is far from a household name and certainly can’t compete with the runaway traction of Ozempic and Wegovy.

“Our whole thing now is amplification, because the biggest feedback we get is, ‘Why haven’t I heard of you?’” Kennedy says. “And of course, that fourth human clinical trial is so important for that amplification of our message across all modalities.”

The NBJ 2024 Awards issue is available at no cost at the NBJ store. Subscribe today to the Nutrition Business Journal.