Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.

Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

SIGN UP LOG IN

Tectonic Therapeutic isn’t your average biotech startup story. For all sorts of reasons.

There’s your billionaire Harvard scientist and philanthropist who’s personally bankrolling much of the operation. The CEO is one of the most prominent women involved in the global drug hunting business. And they have enough collective cachet between them to command virtually as much cash as they might dream of, at a time that biotech dreams are running beyond the fantastic.

But this story isn’t about them right now, so much as it is about a scientist who’s never quite been center stage in the floodlights of biostardom. There’s a whole group of prominent players, though, who believe that’s about to change. Players perfectly happy to gamble some significant coin to give that hope every chance possible of becoming a reality.

Andrew Kruse may not be an immediately recognizable name to you. But to his Harvard colleague Tim Springer, he’s a rock star. They co-founded the Institute for Protein Innovation together, a non-profit that the internationally renowned Springer has been funding with a fortune earned from a remarkable run of successful startups, from his first $100 million out of Millennium to the gusher of wealth that followed his decision to back Stéphane Bancel and the crew at mRNA pioneer Moderna.

Kruse has specialized in work revolving around GPCRs, or G protein-coupled receptors, that make up about a third of all — while still only scratching the surface of potential targets. He was a student of Brian Kobilka at Stanford, who won the Nobel Prize in 2012 for his contribution on the work on GPCRs. And Kruse has published extensively on his lab’s structural analysis of GPCRs, which Springer believes will open the door to a whole new field of drug R&D that can crack open a slew of currently “undruggable” targets to biologics — covering a gamut of both agonists and antagonists.

“We just have unparalleled experience in the biochemistry and biophysics of GPCRs,” says Springer about this new venture of his. “Andrew Kruse is a real star. He went from being a PhD student at Stanford to an assistant professor at Harvard Medical School — he had many papers out of his PhD — and he’s gone on to full professor at Harvard Medical School in 7 years. That is a record at least in modern times. The guy is just amazing. And he’s a nice guy.”

Springer is so convinced by the potential of Kruse’s research that he put up the first $5 million to seed the company 18 months ago. Terry McGuire — the co-founder at Polaris who goes back a long way with Springer — chipped in a million.

Which brings us to the nut of today’s news story.

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

SIGN UP LOG IN

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

SIGN UP LOG IN