Three weeks after taking over as CEO of Lexicon Pharmaceuticals back in 2024, Michael Exton suggested the company close its commercial operations.
He knew the Texas-based biopharma needed to change course, though he jokes that the board may not have been ready for what he had in mind. “I’m not sure if they were prepared for the refresh I wanted to give them,” he told Fierce in an interview on the sidelines of the Fierce Biotech Week conference Tuesday.
Exton had arrived at Lexicon from Novartis, where he had led the relaunch of the company’s heart failure drug Entresto, which had underperformed. Exton said Novartis hoped the treatment could be a $10 billion drug, but had yet to reach these ambitions in four years after debuting in 2015.
“I was the last throw of the dice, because they’d been through several leaders,” he said. “The role was to turn this around.” After navigating the managed care system in the U.S. and competition with generics, Entresto found its footing. In 2025, the drug made $7.7 billion in revenue.
Because of his experience with Entresto, Exton felt that Lexicon’s sole remaining approved drug would never reach the heights the company had hoped for because it wasn’t first in class.
The company had tasted regulatory success when its oral med Xermelo had been approved in combination with somatostatin analog therapy to treat carcinoid syndrome diarrhea in 2017, but Lexicon had sold the therapy to TerSera Therapeutics in 2020. Then in 2023, the biopharma finally secured the FDA green light for Inpefa to reduce the risk of heart failure after a failed attempt to get the SGLT1/SGLT2 inhibitor approved as a Type 1 diabetes treatment.
But Exton knew the world of pharmacy benefit managers and rebates well enough to understand that Inpefa would always face major hurdles to access because incumbent treatments had preceded it.
“It was very clear to me that this was going nowhere, not because Inpefa wasn’t a great drug in that indication, but just because of the vagaries of insurance in the U.S.,” he said.
Lexicon CEO
He set about making difficult decisions and reorganizing Lexicon, reducing headcount from 250 to just 90 people, while restructuring the debt to provide more flexibility, and focusing the company on R&D.
“We needed indications where we can be first or only in our class,” he remembered. “We had to go through tough times, but we needed to keep our eyes on the prize.”
The tough times didn’t end with the restructuring. Lexicon’s latest attempt to get Inpefa approved for diabetes in the U.S.—under the brand name Zynquista—was turned down by the FDA. In November 2024, the company eliminated its commercial field team and promotional efforts for Inpefa and planned activities for Zynquista, delivering on Exton’s promise to make the company an R&D-focused enterprise.
Only a few months later, the biopharma published mixed data for its non-opioid pain prospect LX9211, also known as pilavapadin, in a phase 3 trial. The AAK1 inhibitor was no better than placebo at improving the daily pain score for adults with diabetic peripheral neuropathic pain (DPNP).
Lexicon’s stock dropped to 36 cents in the wake of the news, putting the company in the danger zone of being delisted from the Nasdaq.
Despite the setbacks, Exton knew the pipeline had promise. He saw potential in the pain data and believed that pilavapadin could become a first-in-class treatment that would move the needle in a big way. Throughout the difficult times, Exton said he leaned on a quote, often attributed to Winston Churchill, to keep himself and the team focused: “Success is not final; failure is not fatal: it is the courage to continue that counts.”
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More than a year later, Exton has much to be excited about. Not only is the stock trading at $2.41, nearly seven times higher than its 2025 nadir, but the company secured a $1 billion biobucks licensing deal with Novo Nordisk. The Danish pharma took a shine to LX9851, a small-molecule candidate designed to increase feelings of fullness by inhibiting ACSL5.
It means that Lexicon is in “good shape to go crazy” in the next six to nine months, Exton told Fierce.
Meanwhile, Inpefa is currently in a phase 3 trial for hypertrophic cardiomyopathy, with a readout penciled in for early 2027. “If that trial works out positively in the first quarter of next year, then that will be a significant inflection point for the company and take us back to potentially being a commercial organization.”
And Exton still isn’t ready to give up on his dream of getting the drug approved in the U.S. for diabetes, pointing to evidence that the therapy could also be used in combination with insulin to level out glucose release.
“We’re now on the precipice of resubmitting that NDA with some third-party data by mid-year, and that has the potential, in discussions with FDA, to be approved this year,” the CEO said.
Exton also said that Lexicon’s AAK1 inhibitor pilavapadin has shown promise despite the mixed results last year. “There is a huge unmet need, with about nine million patients in the U.S. diagnosed with DPNP, and 20% of those take oral opioids,” Exton said. “Opioids clearly have great efficacy, but deleterious negative consequences.”
Earlier this month, Lexicon secured a loan facility with Hercules Capital, providing up to $100 million in borrowing capacity. With the new funding and a promising pipeline in the works, Exton reflected on what were not always easy calls to make when remolding the company’s strategy and workforce.
“It sets the development and financial pathway on a very different trajectory,” Exton said. “People may not necessarily like the decisions that I have made, but it’s always done with love.”
