Tony de Fougerolles

A step be­hind its ma­jor ex­o­some chal­lenger, Evox scores $95M round for fi­nal leg of race to the clin­ic

Af­ter years of aca­d­e­m­ic and ear­ly-stage biotech de­vel­op­ment, ex­o­somes fi­nal­ly en­tered the clin­ic last year, when Co­di­ak launched their Phase I/II tri­al in ad­vanced sol­id tu­mors. Now Evox, their chief ri­val in the space, is plot­ting their own path to hu­mans, even if they still have a ways to go.

Evox an­nounced Thurs­day a $95 mil­lion Se­ries C to push their first rare-dis­ease pro­grams in­to the clin­ic in 2022. The round, led by Red­mile Group, will al­so al­low the com­pa­ny to ex­pand in­to new dis­eases and modal­i­ties, in­clud­ing de­liv­er­ing gene ther­a­py and gene edit­ing, CEO Tony de Fougerolles said in an in­ter­view.

Ex­o­somes, tiny bub­bles of fat that func­tion as a postal ser­vice be­tween cells in the body, have be­come a grow­ing fo­cus for drug de­vel­op­ment in re­cent years. Based on stud­ies show­ing that these nanopack­ages can car­ry ge­net­ic ma­te­r­i­al and even pro­teins with­in and across tis­sues, com­pa­nies have tried to turn them in­to de­liv­ery ve­hi­cles for a host of tech­nolo­gies, from old-fash­ioned small mol­e­cules to mR­NA and AAV gene ther­a­py.

Evox, which has now raised over $150 mil­lion in five years, and Co­di­ak, which went pub­lic last year for $83 mil­lion, are the two largest play­ers and as their en­gi­neer­ing ef­forts pro­gressed, they’ve at­tract­ed at­ten­tion from Big Phar­ma and big biotech.

Fougerolles, who helped de­vel­op the first ve­hi­cles for RNA ther­a­pies as one of the first em­ploy­ees at both Al­ny­lam and Mod­er­na, said ex­o­somes have been eas­i­er to en­gi­neer than lipid nanopar­ti­cles — aca­d­e­mics and the body have done a lot of the work for them — but the com­pa­ny has still man­aged to im­prove the amount of pay­load they can de­liv­er by sev­er­al or­ders of mag­ni­tude.

“We’ve en­gi­neered every­thing from a small mol­e­cule to an AAV to an mR­NA, siR­NA, etc. So we kind of have this whole tool­box built out,” he said. “Now we’re in the phase of re­al­ly trans­lat­ing them in­to prod­ucts.”

Take­da and Eli Lil­ly have re­ward­ed Evox ac­cord­ing­ly, each dan­gling over $1 bil­lion for col­lab­o­ra­tions on rare dis­ease and cen­tral ner­vous sys­tem dis­or­ders, re­spec­tive­ly. Co­di­ak has its own deals: with Sarep­ta for a re-dos­ing gene ther­a­py and with Jazz Phar­ma­ceu­ti­cals for can­cer.

Fougerolles said both com­pa­nies have tak­en a broad­ly sim­i­lar ap­proach to en­gi­neer ex­o­somes but far dif­fer­ent ap­proach­es to ap­ply­ing the ex­o­somes they en­gi­neer. Co­di­ak chose im­muno-on­col­o­gy, build­ing out at least six dif­fer­ent can­cer pro­grams. Evox looked at that op­tion and re­ject­ed it as too risky.

Too much is un­known about im­munol­o­gy, and sci­en­tists are still strug­gling to de­vel­op an­i­mal mod­els that trans­late well in­to hu­mans, Fougerolles said. So why pair an untest­ed tech­nol­o­gy in ex­o­somes with high-risk ap­pli­ca­tions?

“Some­one like Co­di­ak has the same ex­o­some plat­form risk, but they’ve al­so now put on ad­di­tion­al risk in terms of, is that the right tar­get in terms of im­muno-on­col­o­gy?” he said.

Evox’s first pro­grams, by con­trast, are in rare dis­or­ders where pa­tients are miss­ing an en­zyme in the urea cy­cle. If their ex­o­some can suc­cess­ful­ly de­liv­er an en­zyme to that pa­tient’s cells, it knows the pa­tient will im­prove and quick­ly. And if the pa­tients don’t, Evox will know what was at fault.

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?

Ex­clu­sive in­ter­view: Pe­ter Marks on why full Covid-19 vac­cine ap­provals could be just months away

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.

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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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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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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.

Janet Woodcock (AP Images)

Janet Wood­cock on if the FDA is get­ting tougher on drug re­views: ‘I don’t think so’

Following a recent string of setbacks for some drug developers, acting FDA commissioner Janet Woodcock said Wednesday that she does not think the FDA is getting more stringent in its reviews of new drugs even as the agency hosts a 3-day advisory committee next week to take a closer look at several accelerated approvals.

“I don’t think so,” Woodcock said when questioned about the tougher stance at a webinar for the Alliance for a Stronger FDA. “I think that what’s happening is that science is moving into fields that typically haven’t seen advances that we’re seeing in other areas, and so I think there is some adjustment that has to be made as people deal with that.”

Sajith Wickramasekara, Benchling via YouTube

Meet Bench­ling, the lat­est uni­corn seek­ing to rev­o­lu­tion­ize the way sci­en­tists do work with the help of the cloud

There’s another unicorn in biotech land, as Benchling and its leading R&D cloud platform pull in a $200 million Series E to help scientists accelerate drug development. In doing so, the company hit a lofty $4 billion valuation — nearly five times what it was worth around this time last year, according to Forbes.

Despite the fact that drug development is becoming significantly more complex, the industry continues to run on paper, emails and spreadsheets, co-founder and CEO Sajith Wickramasekara said in a video on Benchling’s website. The former MIT student sought to change that by creating software that allows scientists to better track, model and forecast their work.

Voting in the 2020 election (AP Images)

The right to vote is fun­da­men­tal — a let­ter from biotech­nol­o­gy in­dus­try lead­ers

Biotech Voices is a collection of exclusive opinion editorials from some of the leading voices in biopharma on the biggest industry questions today. Think you have a voice that should be heard? Reach out to senior editors Kyle Blankenship and Amber Tong.

We oppose all attempts to introduce laws that reduce the rights of US citizens to vote or that restrict them from exercising that right. The right to vote is fundamental to democracy. States that have enacted, or are proposing to enact, legislation to restrict voting are undermining our democracy and posing a threat to our nation. As leaders of the life sciences industry, we stand for what we believe is right for our country, our enterprises, our employees and those who benefit from our work. We join the first groups of business leaders who have challenged these laws and will continue to make our collective voices heard on this matter.

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.