This story is one in an occasional series about advancing discoveries with clinical and commercial potential through collaboration and commercialization.
Medication adherence remains a persistent challenge across many disease areas. Daily oral contraceptive pills allow women to manage their fertility, but this method of contraception relies on a user remembering to take a pill at the same time every day. In a multi-national survey, up to half of patients taking an oral contraceptive reported missing at least one dose over a three-month period. Patients can use combination therapies to help manage HIV and prevent the disease’s spread, but in HIV clinical trials, only about 30 percent of patients stuck to their dosage plans.
What if a patient could take a pill just once a week or even once a month instead of every day? To meet that goal, Giovanni Traverso, MB, BChir, PhD, a gastroenterologist and innovator at the Brigham and MIT, and his colleagues have been working on a way to deliver an oral therapy in a weekly or monthly capsule. In 2015, Traverso and Robert Langer, ScD; Andrew Bellinger, MD, PhD; and Amy Schulman, JD, founded Lyndra Therapeutics to develop, expand and commercialize this platform. Since its founding, the company has formulated 19 therapies in the lab, raised $240 million through investors and partners and grown to more than 150 employees. Currently, there are clinical trials underway to test weekly oral pills for conditions such as schizophrenia and substance use disorder.
“The ability to move so quickly has been remarkable,” said Traverso. “From the beginning, this has been an incredible team, motivated to make it easier for patients to receive medication. Lyndra’s team has grown, and the applications of this delivery system have expanded, but at the heart, it’s a team that remains true to that mission.”
Long before Lyndra Therapeutics was founded, Traverso was engaged in research at the intersection of innovation and clinical applications. He completed his internal medicine residency at the Brigham in 2009 and moved to MGH for his fellowship. He was also conducting research at MIT in the Langer lab, exploring the possibility of designing a capsule that could be folded, swallowed and—once in the stomach—safely stay there while slowly releasing a drug over a sustained period. Traverso and his collaborators tried many different designs, using preclinical models to determine which shape, configuration and materials could work best.
It was during this time that Traverso had an opportunity to meet Bill Gates, who was visiting labs at MIT. Traverso recalls the Bill and Melinda Gates Foundation following up on that conversation during the week of Thanksgiving in 2012, asking him and Langer to submit a white paper on their long-lasting pill research. Traverso and his colleagues sprang into action.
“We iterated quickly,” said Traverso. The team received their first grant from the Gates Foundation in the fall of 2013.
In 2013, Traverso met Bellinger and they began working with polymer chemists. The team started by focusing on tropical diseases, such as malaria. Traverso contacted Joel Katz, MD, director of the Brigham’s internal residency program, for recommendations of infectious disease experts who could help advise the nascent team.
“We had crucial conversations with experts on all aspects of infectious disease,” said Traverso. “In that first year, we attempted many things that failed, but we kept trying, iterating and testing.”
The team needed an easily ingestible capsule that could safely stay in the body. Eventually, they developed a capsule that, once inside the stomach, unfolds into a star-shaped structure too large to pass through the pylorus — the connection between the stomach and the small intestine — and exit the stomach, yet allows food to continue passing through the digestive system. The arms provided rigidity, and the capsule contained polymers and other materials to allow the drug to diffuse out slowly over time.
Advancing Toward the Clinic
Traverso and colleagues published their first paper on the delivery platform in 2015. In 2016, Lyndra began preclinical trials of the platform, providing proof-of-concept data, and in 2017, the company demonstrated that the platform could work in humans. By 2018, a phase 1 clinical trial had begun. Today, Lyndra has programs on drugs to treat schizophrenia, opioid use disorder, pregnancy prevention and malaria eradication that are advancing through phase 1 and phase 2 clinical trials.
Traverso frequently interacted with Lyndra’s team in its early days, and while he remains engaged, his role has shifted as the company has matured. He admires the team that Lyndra has cultivated — many members of whom were recruited when they were recent graduates and have been mentored by experts with both academic and industry experience.
“From a training perspective, it’s critical to demystify the role that industry can play in moving from discoveries made in an academic environment closer to clinical impact,” said Traverso. He recalls a specific moment when that transition was made clear to him: seeing an MRI of the stomach of a human trial participant that showed the star-shaped dosage form he and his colleagues had designed. Traverso described that sight as extremely moving.
“It’s been an incredible experience,” he said. “As a scientist, engineer and physician, what excites me is developing systems that can improve people’s lives. It’s an achievement to publish a paper, but what I personally find most compelling is seeing the ways in which our work can be used to help people.”