Editor’s note: This story is part of our 2022 PharmaVoice 100 feature.
The pursuit of new psychiatric medicines has dogged the biopharma industry for decades. In particular, several drug development setbacks have stalled innovation for the treatment of mental health conditions, causing many major pharma players to abandon the market. But where others have seen failure, Andrew Miller, the founder and chief operating officer of Karuna Therapeutics, has found potential rewards.
According to Miller’s nominator, there was one investigational drug in particular — xanomeline — that helped the entrepreneur realize some advances could have been overlooked by other companies. Investigated by Eli Lilly in the ‘90s, xanomeline showed promise as an antipsychotic treatment that improved cognitive function in patients with Alzheimer’s. Yet, Lilly ultimately shelved the drug due to tolerability issues.
Going back to the drawing board, Miller’s nominator says he “spearheaded the assessment of more than 7,000 possible combinations of muscarinic receptor agonists and antagonists to find an optimized combination that could help address this significant patient need.”
“What he found was that xanomeline paired with trospium, a muscarinic antagonist active in the periphery, stood out to be a promising combination that had the potential to maintain the robust antipsychotic effect seen in prior studies with xanomeline, but offset the tolerability concerns associated with xanomeline alone,” Miller’s nominator says.
With this new investigational treatment — dubbed KarXT (xanomeline-trospium) — in hand, Miller founded Karuna in 2009. He was just 27 at the time.
Today, KarXT is in late-stage development for schizophrenia and psychosis related to Alzheimer’s disease, and the company has four other drug candidates in preclinical studies.
“The purpose of founding the company is reflected in its name: Karuna is the Sanskrit word for compassion or action to relieve the suffering of others. That is the vision for the company — to introduce a treatment that can make a difference in the lives of people who are so deserving of compassion.”
Founder and chief operating officer, Karuna Therapeutics
In 2016, Miller transitioned to working at Karuna full time as it was on track to blossom into a late-stage company, all while navigating complex scientific, technical and regulatory steps with his team.
After Karuna’s IPO in 2019, Miller’s nominator says the company became one of the “top-performing IPOs” of the year across all sectors. Karuna also now has a market cap greater than $7 billion. Miller says over the last few years of “rapid growth,” the company’s headcount has increased from 19 to over 150 employees, causing him to change his approach to leadership.
“As Karuna has rapidly grown, my role too has changed to meet the new needs of our company and team,” he says. “Things that once came naturally now need purposeful attention — such as effective cross-functional communication and maintaining the company culture.”
In general, he says he strives to “stay away from a hierarchical approach to leadership” and encourages colleagues to venture outside of conventional thinking.
“As we grow, I do everything I can to instill the sense of commitment and passion that drove me to found Karuna to ensure that — as a company — we are collectively driven by the unifying mission to create and deliver transformative medicines for people living with psychiatric and neurological conditions,” he says.
The brand Miller most strongly identifies with is The North Face. He says the company, whose mantra is “never stop exploring,” encourages its customers to “push limits, discover something new and reach for their dreams.” He says while Karuna operates in a completely different market, the company also “encourages exploration, innovation and pushing the boundaries of what is possible to bring meaningful new treatments to people who need them.”