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Msg  35111 of 35117  at  2/16/2023 9:06:44 AM  by


Interesting Endpoints article

 What does it say about the leading edge status of Alnylam research when these guys all leave to start something else?
February 16, 2023 06:30 AM EST
FinancingStartupsCell/Gene Tx
'Rare outliers': Feng Zhang eyes a new path to genetic medicine delivery with ex-Alnylam leaders and $193M
Kyle LaHucik
Associate Editor
Marquee CRISPR scientist Feng Zhang, two-decade Alnylam oncology head Akin Akinc and seasoned biotech guru John Maraganore have come together for a new bet on gene editing, aiming to go beyond the scope of the existing crop of clinical-stage tools.

They hope to deliver big time — attempting to upend where potential therapeutic gold mines can go in the body, how they get shuttled and the types of diseases the long-hyped genetic medicine field can treat.

With $193 million to start, Aera Therapeutics’ sights are set beyond just liver, blood and eye tissue. With a new virus-like delivery method, going against the challenging grain of viral and lipid nanoparticle transportation methods, Aera thinks other tissues can be tapped into: the brain, kidney, lung, muscle, heart and more. But they’re likely years away from in-human studies, meaning there are little data to show for their hypothesis just yet.



Jason Shepherd
At the core is Zhang, surrounded by his team’s findings as well as research out of the University of Utah’s Jason Shepherd. Zhang, the MIT researcher and repeat biotech entrepreneur (think Editas Medicine, Beam Therapeutics, Arbor Biotechnologies), has been working for years to plant the seeds for his latest venture, which caught the eyes and ears of Bob Nelsen at ARCH Venture Partners and Issi Rozen at Alphabet’s GV, whose firms have teamed up on the whopping megaround foundation for Aera.

The biotech officially emerged Thursday, but people in the know had previously spilled details to Business Insider last fall and earlier this month.

The 50-employee startup comes from Zhang’s work and the expertise consumed via an acquisition of Shepherd’s biotech, Lux Capital-backed VNV (virus not virus), which was doing similar work based on the Utah researcher’s 2018 Cell paper that caused Zhang to essentially do a double take. Lux Capital’s Adam Goulburn filed the corporate docs for VNV in August 2018 and was the founding CEO until January 2021 and has since launched a new life sciences venture firm.

In an interview with Endpoints News, Zhang called Shepherd’s team’s findings, in which a protein dubbed ARC was discovered to form virus-like capsid structures, “cool.” So he investigated and dug “a little deeper” into potential proteins that could be harbingers of capsid-like structures that ferry genetic medicines to areas of the body previously closed off to gene-editing tools.

Following Shepherd’s work, Zhang’s lab published their initial findings of similar work on another protein, named PEG10. They figured out the proteins can package RNA based on a specific motif found on mRNA and link onto other RNAs to create virus-like particles. That way, the famed CRISPR Cas9 could be delivered into cells using a human protein, as compared to a virus, he said.

With the help of some of biotech’s blue-chip bankrollers, ARCH and GV, the findings from Zhang’s lab flourished into startup mode.

“What we wanted to do was assemble the best possible company to take this technology forward, and given that VNV had similar interests, it made sense to join efforts and move forward,” said Zhang, of Harvard and MIT’s Broad Institute. Shepherd is one of Aera’s scientific advisors.

Like VNV, there are a host of other labs and biotechs in the field, Zhang acknowledged, attempting to create new stories in the gene-editing saga. The field includes the incumbents like Editas, Intellia and CRISPR Therapeutics and newer entrants like Beam, Verve Therapeutics, Tessera Therapeutics and the somewhat stealthy Nvelop Therapeutics, from Harvard’s Keith Joung and David Liu, which has secured $100 million so far, per Pitchbook data. Newpath Partners, Atlas Venture and F-Prime Capital are bankrolling the biotech, which touts to also have come up with new gene editing delivery tech.

John Maraganore
Leading the charge at Aera is Akinc, a nearly 20-year veteran of Alnylam who joined the RNAi pioneering biotech in its early days and saw it through five drug approvals up to last fall when he traded in his SVP and head of oncology hats after Zhang came calling in the summer. Chairing the board is Akinc’s former boss, Maraganore, the famed founding CEO of Alnylam.

“In a lot of ways, this feels a lot like going back to the early days, maybe 2004, at Alnylam, where we know we have an incredibly powerful modality on our hands, but it was really about figuring out how to deliver it,” Akinc said in a joint interview Wednesday afternoon with Zhang.

Can he repeat another five drug approvals in about 20 years?

“That’s the goal. That’s the ambition is to become one of those rare outliers,” Aera’s chief executive said. “That’s definitely my objective is to try to do this all over again but definitely know that’s not easily done in this space.”

It’s still early days in the Boston upstart’s lab, as scientists explore a bevy of potential routes, whether that’s bringing small and/or large nucleic acid payloads into the clinic, Akinc said. Antisense oligonucleotides, siRNAs, mRNA, gene therapy, gene editing “in all its various forms,” he said, bookending the list of buzzwords.

Within Aera’s grasp are what Akinc refers to as potential treasures for genetic medicine delivery, proteins like PEG10. Hence the name, a play on an abbreviated version of the Latin word Aerarium, or the public treasury of ancient Romans.

Rome wasn’t built in a day. Aera’s been in the works for years, with fall 2021 marking the official go-forth for Zhang’s idea, early 2022 beaconing the financing haul, and early 2023 serving as the public unveiling period. The $193 million should help the lights shine bright in Aera’s labs for multiple years, Akinc said, adding that 30 more staffers will join this year, but no C-suite roles are currently being hunted.

In conjunction with the financing news, Akinc, Nelsen, ex-Vertex president Vicki Sato, GV general partner David Schenkein and Lux Capital managing partner Josh Wolfe have landed seats in the boardroom. Rozen nabbed a board observer post, and Zhang holds equity.

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