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Photo: Leslie Leinwand (left), distinguished professor of molecular, cellular and developmental biology at the University of Colorado Boulder, converses with graduate student Skip Maas (right), holding two pythons. Photo by Patrick Campbell, ���Ҵ�ý�ƽ������.

Internationally renowned cardiac researcher and serial entrepreneur Leslie Leinwand has revolutionized understanding of the heart through her decades-long mission to bring innovations from the lab bench to patient bedsides — and with billion-dollar “unicorn” spinouts Myogen, MyoKardia and, most recently, Kardigan.

After speaking at a medical conference recently, Leslie Leinwand,��distinguished professor of molecular, cellular and developmental biology at the University of Colorado Boulder, met an appreciative attendee. “She was not a physician or scientist; she was a patient,” said Leinwand. The woman had suffered from hypertrophic cardiomyopathy (HCM), a common inherited cardiac disorder that prevents activities that strain the heart. That is, until she started taking mavacamten (CAMZYOS®), a therapeutic developed to treat the underlying mechanism of the disease based on research done in Leinwand’s ���Ҵ�ý�ƽ������ lab. “She came up to me afterward, and she said, ‘I couldn’t walk up and down the steps to get onto the subway; I can now do it without even thinking about it,’” said Leinwand.

That moving meeting between researcher and patient was decades in the making. Leinwand, founder and head of the��Leinwand Lab ���Ի���executive scientific officer of ���Ҵ�ý�ƽ������ BioFrontiers Institute, was fascinated by genetics by the time she went off to college in the 1970s and has been passionate for nearly as long about unraveling the genetic aspects of HCM, which is the leading cause of sudden death in young people, as well as a chronic, progressive disease that in some people can be asymptomatic.��

Leinwand calls HCM “a big sick heart that runs in the family,” affecting as many as one in 500 people worldwide. The condition causes thickening of the heart wall and reduced blood flow into and out of the heart. HCM is also the most common cause of sudden death among athletes, who often don’t know they have the disease until their hearts are taxed to a lethal degree. What ultimately causes the disorder had long been a heartbreaking mystery — until a team of scientists, including Leinwand, cracked the code.��

From bench to bedside — with unicorns

The heart is a big muscle that beats about 100,000 times a day, and the motor that drives that contraction is a protein called myosin. Leinwand has been studying cardiac myosin for most of her career, and since 1995 at ���Ҵ�ý�ƽ������, having had the sense early on in her research that a malfunction in the protein played a role in heart disease. When myosin mutates, in fact, it can produce the too-fast, too-powerful heartbeat characteristic of HCM. “My lab studied how certain muscle mutations lead to disease,” said Leinwand, “and how a small DNA change leads to an often fatal crisis in the heart.”��

Still, into the 2000s, no one knew how exactly the heart’s myosin motors were affected by gene mutations, and the only treatments for HCM were medications to slow heart rate, surgery to trim excess heart muscle or, in extreme cases, a heart transplant. HCM sufferers led sedentary yet anxious lives, trying to prevent the worst-case scenario. Then Leinwand’s lab, one of just a handful in the world studying cardiac myosin at the time, devised a game-changing system for producing lab-made cardiac myosin motors engineered with mutations. Those copies proved to be a critical step in studying the effects of DNA glitches that made the protein overreact, and in identifying them as a promising target for treatment.��

Those groundbreaking discoveries led Leinwand to co-found MyoKardia in 2012, with colleagues at Stanford and Harvard. The company was centered on developing a therapeutic for HCM that essentially targeted myosin activity and pumped the brakes on the heart’s overactive motor.

Leinwand said the clinical trials of mavacamten exceeded the scientists’ expectations. “It was even better than what we had hoped for; we thought we might be able to slow the progression of this disease, but we’re seeing reversal of the disease,” said Leinwand. “In that population of people who respond very well, it’s been life-changing and life-saving.” In 2020, Bristol Myers Squibb acquired MyoKardia for $13.1 billion and brought the myosin inhibitor to market as CAMZYOS^® two years later.

By the time she co-founded MyoKardia, Leinwand was already a seasoned entrepreneur. Just a year after arriving at ���Ҵ�ý�ƽ������, she co-founded Myogen with the late Michael Bristow, then a professor of cardiology at what is now the , and two colleagues at the University of Texas Southwestern Medical Center.��

Leinwand credits Bristow, then head of the division of cardiology, with getting her interested in biotechnology. “At one point, he said to me, ‘How’d you like to start a company to treat heart failure?’ And I said, ‘I know nothing about starting companies,’” said Leinwand. “He said, ‘Well, luckily for you, I do, and I’ll teach you’ — and we were off to the races.”��

Myogen focused on discovering, advancing and commercializing drugs for the treatment of heart failure and related cardiovascular diseases. One of its major successes was a therapy called ambrisentan, developed to treat pulmonary arterial hypertension (PAH), a progressive disease causing extreme fatigue and breathlessness. Myogen’s savvy strategy of licensing products developed by other companies and then repurposing them for use in the heart caught the attention of private investors, then Gilead Sciences, which bought the company for $2.5 billion in 2006. Soon after the purchase, ambrisentan gained U.S. Food and Drug Administration approval (marketed as Letairis®) and became a standard-of-care therapy for PAH. “That was very satisfying, because there weren’t any treatments for it, and PAH was quite lethal. Many young women, in particular, were dying as a result of that disease,” said Leinwand. “So it was a success commercially and from the patient standpoint.”

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The immense commercial success of Myogen and MyoKardia already makes Leinwand a rarity, said��,��senior associate vice chancellor for innovation and partnerships at ���Ҵ�ý�ƽ������. “As a biotech innovator, Leslie has reached legendary status,” he said. That position is based on Leinwand’s prolific discoveries, life-saving drug developments and the success of her commercial ventures, he said.��

“One of the really remarkable things about Leslie is that Myogen, MyoKardia and now Kardigan are all among [���Ҵ�ý�ƽ������] unicorns,” said Rees, referring to the status companies achieve when they reach a valuation of $1 billion. “Having one unicorn is incredible. Building three over the course of a career is almost unheard of.”

Luckily for those within and outside the university, Leinwand is an unstoppable innovator, said Rees. In 2023, she co-founded Kardigan with MyoKardia alumni, a “heart health” biotech company focused on developing therapeutics that prevent and cure heart disease, in addition to treating it. Kardigan is advancing three clinical-stage drug candidates targeting hard-to-treat cardiovascular diseases. The company — Leinwand’s extraordinary third unicorn — had raised nearly $600 million in private venture funding by late last year and, in June, Leinwand and colleagues were ringing the Nasdaq opening bell in Times Square to mark Kardigan’s initial public offering of $400 million.

Going out on the edge

By her own admission, Leinwand doesn’t sleep much and, when she invariably wakes in the middle of the night, she jots down thoughts in a notebook kept by her bedside. “I actually think sleep is a waste of time,” she said. Even today, the waking hours provide her with opportunities to pursue her passion.����

“For me, that passion for discovery and translating research into something that could be useful for humans in both health and disease is what drives me,” said Leinwand. “I feel like I’m still learning and I look forward to that.”

Throughout her career, Leinwand has also been a strong advocate of encouraging others to follow their passion toward discovery. Over the past few decades, in the Leinwand Lab and beyond, she has mentored hundreds of scientists, some of whom are also now leaders in cardiac research. “Clearly, I’ve had a lot more interest than I ever thought I would in developing these companies, but I never wanted to be out of academics,” said Leinwand. “I didn’t want to give up mentoring students; I love that too much.”

By design, the Leinwand Lab and later the BioFrontiers Institute have always taken an interdisciplinary approach to human health and disease. Leinwand attributes much of her success to working with others at the university who can look at a shared problem from a different angle. “Human health is very complex and requires true interdisciplinary approaches. Being able to learn from people who do and think a little bit differently [is important],” she said. That collaborative environment encourages people to “go out on the edge,” she said, where answers to complex questions often lie.��

Leinwand’s mentorship and policy of academic freedom drew����to her lab when he was pursuing his PhD several years ago. And then there were the pythons in residence in the Leinwand Lab. “The snakes were one of the things that really got me,” Gugel said. “And yeah, they are pretty awesome.”��

The “Python Project” launched two decades ago at the Leinwand Lab to study the remarkable snakes whose heart size increases 25 percent or more after eating a massive meal — then shrinks back to normal. That led to Leinwand’s short-lived startup called Hiberna, which looked at translating research on “metabolic depression” (like that experienced by hibernating animals) into treatments that could protect the heart during adverse events by slowing metabolism in a controlled way. Her lab continues to study the ways in which understanding a python’s powerful, pliable heart may inform human health.��

More recent python research led to another Leinwand Lab startup, Arkana Therapeutics, co-founded in 2025 by Gugel, Leinwand,����(a postdoctoral fellow in the Leinwand Lab at the time) and Jonathan Long at Stanford. The company is based on research into pythons’ response to eating a big meal, which, in the wild, can equal their body weight. “They can really eat one of the biggest meals of any animal in the animal kingdom,” said Gugel, “so we wanted to see what happens to their physiology and what kind of molecules they were producing.”��

Photo: Members of Arkana Therapeutics with their prize-winning check at the 2025 Lab Venture Challenge. From left: , ��and .

Ultimately, they discovered a molecule that increases 1,000-fold after the python eats, acting as a natural appetite suppressant. That science laid the groundwork for Arkana’s metabolite-based therapeutics for obesity, which are now in the proof-of-concept phase.

For Gugel, now CEO of Arkana, Leinwand has been a north star in getting the company off the ground. “She’s been huge both on the scientific side as a grad student, and especially as I’ve been transitioning into this startup role,” he said. Leinwand has opened up her network on the science and business fronts, said Gugel. “She’s walked down this road so many times before with previous companies and is so helpful in that regard,” he said.

Gugel and his team have also benefited tremendously from the commercialization arm of the campus, Venture Partners at ���Ҵ�ý�ƽ������, which didn’t exist when Leinwand launched her first companies but now helps would-be entrepreneurs follow in her footsteps.��

“Venture Partners has really helped lay out the roadmap of ‘here are all the things you need to do, and all the sources of funding you can get,’” said Gugel. “They stand out compared to what I’ve seen at other universities in terms of their professionalism and how good they are at what they do.”��

Arkana has participated in several Venture Partners programs, including the 2025��Lab Venture Challenge (in which it won $127,500); the 2026��Ascent Deep Tech Accelerator, supporting business formation, market strategy and fundraising; and it was among the first recipients of a new translational funding program that provided up to $50,000 per project to advance promising, early-stage therapeutics with strong commercial potential.

Leinwand was reflective when asked what those moments of discovery are like — when a scientific mystery is solved, or a person reaches out to you whose life has been improved by a therapeutic you helped develop. “[Those moments] are indescribable in the sense that you have this sort of feeling of satisfaction, that you are glad you stuck with this idea and didn’t get distracted. They keep you going,” she said. “I absolutely love what I do.”
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