With a background in pharmacology, Ritu Lal has worked at the likes of Abbott and Roche, ushering drugs from early discovery through FDA approval three times. But to Lal, who has filed more than 15 IND applications in her career, three approvals in 23 years was still frustrating—even in the context of biopharma’s low conversion rate from research programs to approved drugs.
“It kind of sucks, but it’s the industry standard that one out of 10 drugs makes it to FDA approval,” Lal told FierceBiotech. That record got her thinking about drug compounds and diseases—and how to get drugs to market and to patients more quickly.
“We did a search of drugs that were attractive from a commercial and developmental standpoint,” she said.
That hunt brought her back to p38alpha kinase inhibitors, a class of drugs she had worked on at Roche in the early 2000s—alongside numerous other biopharma companies trying to do the same.
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“At that point, none of us succeeded either because of safety issues or loss of efficacy,” she said.
But she stumbled upon research out of the University of Maryland, Baltimore—where, coincidentally, she’d earned her Ph.D. in pharmaceutical sciences—that targeted p38alpha kinases in a new way.
“It was almost serendipity: We came across the p38alpha-specific, substrate-selective compound at the University of Maryland,” Lal said. "The inventors and tech transfer office saw the synergy and we established a teamlike working relationship."
It was a way to move forward a class of drugs that “we—and when I say ‘we,’ I mean the whole industry—could not develop because of potential efficacy issues,” she said.
The Maryland team used computer-aided design to synthesize new molecules that would bind selectively to p38alpha kinases, which are just one type of the p38 kinase enzyme.
“Using sophisticated computational drug design technology, they were able to find a pocket in the kinase enzyme. The compounds bind to this pocket and avoid hitting off-targets,” Lal said. This specific targeting could be the key that unlocks this class of drugs. Lal likens the previous p38-targeting compounds of the early 2000s to a hammer, hitting every single form of the enzyme and blocking functions that are useful to the body.
Lal founded GEn1E (pronounced “genie,” as in, “genie in a bottle”) Lifesciences in 2018 and licensed a set of compounds from the University of Maryland. The Bay Area biotech is first taking aim at acute respiratory distress syndrome, a disease in which fluid leaks into the lungs, making it difficult or impossible to breathe.
"Approximately 200,000 patients in the U.S. have this disease and 40% of them die, which is devastating. There is no FDA-approved treatment, literally nothing. I spent a week in the ICU shadowing a pulmonologist and saw firsthand that there’s nothing to help them,” Lal said.
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Care consists of supporting the patient while their lungs heal and can include sedating them, using a ventilator to aid breathing or prescribing diuretics to help them get rid of excess fluid in the body, according to the American Lung Association.
“The burden to society for this disease is huge. It’s $100,000 per patient and it's a $20 billion cost to society, just in the U.S. We not only want to help patients, but also reduce the burden to hospitals,” Lal said.
Preclinical data out of the University of Maryland show that its p38alpha kinase drugs strengthen the endothelial layer in the lungs to prevent fluids from filling there, and they inhibit inflammation that can cause lung damage. Next up, the company is driving the program toward IND-enabling studies and then, the clinic.
GEn1E is launching out of Y Combinator with a little more than $1 million in seed funding. A self-professed type A personality, Lal says her experience at Y Combinator has made her “type A on steroids.”
“I love the energy, the positivity and learning from each other—there are a whole bunch of companies, therapeutic and otherwise, in our batch,” she said.
“We’re chugging along with these compounds and will be starting the animal preclinical PK and safety studies and hopefully get IND-enabling studies soon. We have some great lead compounds which have shown efficacy and PK and we are in the process of selecting our lead compound … It’s very exciting because a lot of work has already been done, we are not starting from scratch,” she said.
Though it’s still working on generating the data to support further programs, GEn1E reckons it’s got a platform on its hands.
“This is all based on the literature because we haven’t generated our own data yet, but p38alpha kinase inhibitors work for muscle stem cell regeneration and they work for hearing loss, which I think is great. They also work for other diseases like Werner syndrome, Duchenne muscular dystrophy and Alzheimer’s,” Lal said. “It’s still early, but there’s so much potential."
She co-founded GEn1E alongside Clint Webb, the chief operating officer. The duo recently hired a head of research, Wendy Luo, to join their team of 10 people who work on a part-time basis as consultants, along with the company's advisory team. Their functions span the gamut from toxicology and clinical operations to manufacturing and regulatory. The company is looking to hire four or five more people but aims to stay “lean and mean.”
“We have a number of CROs we’re working with—a few of them have invested in our company, in fact,” Lal said. “We want to keep this model with a virtual team but hire the key people we need and manage the CROs very well. That way, we can stay cost-efficient and time-efficient and get things done.”
And, having worked on p38alpha kinase inhibitors the first time around, Lal is confident she’s the right person for the job.
“Having lived through all of these compounds, I know how to develop them. I understand their potential and know how to solve some issues we had the last time that we—the collective we, the whole industry—had working on these compounds,” she said.