Jon Congleton, Mineralys

Min­eralys emerges with a new take on an old idea for the treat­ment of hy­per­ten­sion and $40M to play with

BT Slings­by

Al­dos­terone, a hor­mone linked to in­creased blood pres­sure, has long been a tar­get of in­ter­est for the treat­ment of hy­per­ten­sion, but se­lec­tiv­i­ty has been a chal­lenge. Now a new com­pa­ny has emerged from stealth to im­prove where oth­ers have failed.

Min­eralys Ther­a­peu­tics un­cloaked ear­ly Mon­day morn­ing with $40 mil­lion in Se­ries A funds to prep their lead can­di­date —  a se­lec­tive al­dos­terone syn­thase in­hibitor li­censed from Japan’s Mit­subishi Tan­abe — for a piv­otal study. The com­pa­ny was launched by Catalys Pa­cif­ic, the VC firm founder BT Slings­by put to­geth­er to cre­ate new biotechs around Japan­ese in­no­va­tion.

Al­dos­terone syn­thase in­hi­bi­tion is not a new idea. No­var­tis, Eli Lil­ly and Boehringer In­gel­heim have all pur­sued it, Slings­by said. At high­er lev­els, al­dos­terone ba­si­cal­ly tells the body to re­tain more sodi­um, and thus more wa­ter, lead­ing to an in­crease in blood vol­ume and pres­sure. CEO Jon Con­gle­ton com­pared the sit­u­a­tion to a wa­ter hose: The more wa­ter in the hose, the high­er the pres­sure.

The idea is to in­hib­it CYP11B2, an en­zyme re­spon­si­ble for al­dos­terone syn­the­sis. But the chal­lenge is do­ing so with­out off-tar­get ef­fects. An­oth­er en­zyme in prox­im­i­ty, CYP11B1, con­trols the syn­the­sis of cor­ti­sol. If a can­di­date isn’t se­lec­tive enough, it could in­hib­it both path­ways — and re­duc­ing cor­ti­sol es­sen­tial­ly coun­ters the blood pres­sure low­er­ing ef­fect of al­dos­terone re­duc­tion, Con­gle­ton said.

From the re­sults of four Phase II tri­als con­duct­ed by No­var­tis and pub­lished back in 2013:

Un­for­tu­nate­ly, the ob­served in­crease in 11-de­oxy­cor­ti­sol lev­els in­di­cat­ed off-tar­get in­hi­bi­tion of the 11β-hy­drox­y­lase ac­tiv­i­ty of CYP11B1 that re­sult­ed in the stim­u­la­tion of the HPA feed­back ax­is.

Min­eralys be­lieves it has a more se­lec­tive al­dos­terone syn­thase in­hibitor than past at­tempts. The biotech is about to head in­to a Phase II proof-of-con­cept study in Q2, and Con­gle­ton ex­pects to read out da­ta in the sec­ond half of 2022 which he hopes will pave the way for a piv­otal study launch at the be­gin­ning of 2023.

The Se­ries A funds should al­low the com­pa­ny to do that, as well as pre­clin­i­cal CMC and clin­i­cal phar­ma­col­o­gy work, and have cash go­ing in­to 2023, he said.

Con­gle­ton joined Min­eralys back in Oc­to­ber as em­ploy­ee No. 1. That was short­ly af­ter he left Im­pel Neu­roPhar­ma, where he served as pres­i­dent and CEO. The com­mute led him to leave Im­pel, he joked, adding that week­ly trips from Philadel­phia to Seat­tle were weigh­ing on him. But what at­tract­ed him to Min­eralys was the chance to bring a tar­get­ed ap­proach to the di­ag­no­sis, man­age­ment and treat­ment of hy­per­ten­sion.

In Jan­u­ary, the com­pa­ny tapped mi­Ra­gen, Ver­tex and No­var­tis In­sti­tutes for Bio­med­ical Re­search vet­er­an David Rod­man as CMO.

“We think re­al­ly bring­ing a more tar­get­ed ap­proach to the di­ag­no­sis man­age­ment and treat­ment of hy­per­ten­sion is long over­due,” Con­gle­ton said.

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

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.

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Barbara Weber, Tango Therapeutics CEO (Tango)

It takes two to Tan­go: The biotech us­ing CRISPR to dis­cov­er new can­cer gene tar­gets rides a $353M SPAC deal to Nas­daq

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

The latest biotech-SPAC deal has arrived, and it’s dancing its way to Nasdaq to the tune of several hundred million dollars.

Tango Therapeutics and its CRISPR-focused search for new cancer genes is reverse merging with Boxer Capital’s blank-check company, the biotech announced Wednesday morning. With a spotlight on three lead programs, Tango expects total proceeds to equal about $353 million in the deal, which includes the roughly $167 million held in the SPAC and an additional $186 million in PIPE financing.

Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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Anand Shah (FDA)

For­mer head of FDA’s med­ical and sci­en­tif­ic af­fairs on Covid: ‘FDA has nev­er been test­ed like this’

Anand Shah has served the American public in a unique way, crisscrossing over the last two administrations between serving as an attending radiation oncologist focused on prostate cancer at NIH, serving as CMO at the Center for Medicare and Medicaid Innovation, and most recently, leading the FDA’s operations on medical and scientific affairs from within the commissioner’s office.

Shah, who stepped down from the FDA in January, caught up with Endpoints News in a phone interview on Tuesday afternoon, offering his thoughts on the agency’s latest decision to pause the J&J vaccinations in the US, and reflecting on his time at an agency during this once-in-a-lifetime pandemic.

Kristin Fortney, BioAge Labs CEO

An­ti-ag­ing biotech up­start plucks a drug from Am­gen's dis­card pile, piv­ot­ing from heart fail­ure to mus­cle con­di­tions

Back in April 2019, Amgen quietly shut down a Phase I trial for a drug named AMG 986. There was no safety concern; the molecule just didn’t hit the mark on helping the small band of heart failure patients who received it.

A small biotech, though, believes it would stand a chance in the burgeoning anti-aging field.

BioAge Labs has licensed AMG 986 — now renamed BGE-105 — with plans to parlay the existing IND into a quick Phase I trial teasing out the pharmacodynamic effects and set the stage for mid-stage tests focused on acute muscle indications.

UP­DAT­ED: J&J paus­es vac­cine roll­out as feds probe rare cas­es of blood clots

The FDA and CDC have jointly decided to stop administering J&J’s Covid-19 vaccine after reviewing data involving six reported US cases of a rare and severe type of blood clot in individuals after receiving the vaccine.

CDC will convene a meeting of its Advisory Committee on Immunization Practices on Wednesday to further review these cases and assess their potential significance. “FDA will review that analysis as it also investigates these cases. Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research and Anne Schuchat, Principal Deputy Director of the CDC, said in a joint statement Tuesday morning.

Patrizia Cavazzoni, new CDER director

Pa­trizia Cavaz­zoni named per­ma­nent di­rec­tor of CDER, adding to ques­tions around where Wood­cock will end up

Patrizia Cavazzoni on Monday became the permanent director of the FDA’s Center for Drug Evaluation and Research, which puts to rest the idea that Janet Woodcock, Cavazzoni’s predecessor, might return to lead CDER if she isn’t made permanent commissioner.

Woodcock, who’s currently serving as acting commissioner and principal medical advisor to the commissioner, a position she was detailed to last year, may not make the move to permanent commissioner because of lingering questions from Senate Democrats. She previously served as director of CDER since 1994. Cavazzoni took over as acting director of CDER when Woodcock moved over to Operation Warp Speed to run the therapeutics side of the Trump-era program.

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Min Li, SciNeuro CEO

Eli Lil­ly seeds a well-con­nect­ed Chi­na neu­ro start­up with drugs aim­ing at where Bio­gen, Voy­ager missed

When Min Li took the wraps off a $100 million round for his Bob Nelsen-backed startup last December — as with most biotech CEOs when they launch — he left a couple cards unturned.

Keen to build a first-of-its-kind neuro play in China, the GlaxoSmithKline R&D vet already had a good idea of which assets he wanted to in-license for SciNeuro, conducting Zoom negotiations from the East Coast office that he’s been somewhat stuck in since JP Morgan early in the year. Now, he’s finally ready to shine a spotlight on the first program: a slate of alpha-synuclein targeted antibody therapies from Eli Lilly.