Bay­er fronts $65M Se­ries A for Metageno­mi, a gene ther­a­py biotech aim­ing to find new CRISPR en­zymes

Gene edit­ing is all the rage in biotech these days, with the field grow­ing in promi­nence es­pe­cial­ly af­ter this year’s No­bel Prize in Chem­istry was award­ed to two pi­o­neer­ing CRISPR sci­en­tists in Em­manuelle Char­p­en­tier and Jen­nifer Doud­na. And now, Bay­er’s in­vest­ment arm is go­ing all-in on a new gene edit­ing out­fit.

Leaps by Bay­er is co-lead­ing a $65 mil­lion Se­ries A round for Metageno­mi, a biotech launched by UC Berke­ley sci­en­tists that emerged from stealth on Thurs­day. Hum­boldt Fund is co-lead­ing the round with Leaps. Metageno­mi, which will be run by Berke­ley re­searcher Bri­an Thomas, is look­ing to de­vel­op a “tool­box” of both CRISPR- and non-CRISPR-based gene edit­ing sys­tems be­yond the Cas9 pro­tein typ­i­cal­ly seen in the field these days.

Bri­an Thomas

“The goal for Metageno­mi is re­al­ly to be able to do any type of gene edit­ing,” Thomas told End­points News. “Whether that be knock-ins or knock-outs that are com­pa­ra­ble to the cur­rent gene edit­ing ca­pa­bil­i­ties, but al­so to be able to do base edit­ing through an en­gi­neer­ing ca­pa­bil­i­ty, as well as to be able to in­te­grate larg­er pieces of DNA that will al­low us to pro­vide safer gene edit­ing.”

Oth­er in­vestors in the Se­ries A in­clud­ed So­zo Ven­tures, Agent Cap­i­tal, In­Cube Ven­tures and HOF Cap­i­tal.

Dur­ing his time at Berke­ley, Thomas was work­ing in the lab of Jill Ban­field, Metageno­mi’s sci­en­tif­ic co-founder, whose re­search fo­cused on find­ing new CRISPR en­zymes in ex­ot­ic bac­te­ria. Now at Metageno­mi, Thomas’ goal is to ap­ply ma­chine learn­ing on a broad scale to mine through the genomes of these mi­croor­gan­isms, search­ing for new nu­cle­as­es that can be used in gene ther­a­pies.

Thomas says the com­pa­ny has found over 100 po­ten­tial en­zymes in the past year as it’s been build­ing out its data­base in stealth. The main ad­van­tage of these sys­tems, Thomas said, is that many — if not all — are much small­er than Cas9, with some be­ing less than half the size. That would al­low for much more pre­cise med­i­cines that lim­it the off-site tox­i­c­i­ty some­times seen with cur­rent gene ther­a­pies.

“The en­zymes we have are re­al­ly able to out­per­form the cur­rent sys­tems in terms of edit­ing ef­fi­cien­cy,” Thomas said. “We’re get­ting edit­ing ef­fi­cien­cies at greater than 90% and some­times greater than 95%.”

It re­al­ly comes down to the sci­ence of metage­nomics, from which Metageno­mi gets its name, Thomas said. Go­ing be­yond ge­nomics, where you start with a lab cul­ture, metage­nomics in­stead looks at the ge­net­ic ma­te­r­i­al re­cov­ered from soil, which con­tains the thou­sands of or­gan­isms that Metageno­mi hopes to map out.

Juer­gen Eck­hardt

Thomas proved so suc­cess­ful at pitch­ing his com­pa­ny, he poached away one of Leaps’ ex­ec­u­tives to be Metageno­mi’s chief busi­ness of­fi­cer. De­spite that, Bay­er is par­tic­u­lar­ly ex­cit­ed about this start­up and Leaps chief Juer­gen Eck­hardt be­lieves Metageno­mi could be at the fore­front of the next gen­er­a­tion of gene edit­ing.

“You look at gene edit­ing and you have these first-wave com­pa­nies, they are all based on one de­tail: CRISPR Cas9,” Eck­hardt said. “What Metageno­mi has, they are sit­ting on thou­sands of nu­cle­as­es that will have a range of fea­tures that may be op­ti­mized for what CRISPR can’t be able to do. I think that’s why this is the next two, three, four, five waves of gene edit­ing are right here.”

Metageno­mi is still an ear­ly-stage com­pa­ny and Thomas isn’t di­vulging what kinds of drugs they’re aim­ing to de­vel­op as of yet, but not­ed a broad in­ter­est in can­cers and im­muno-on­col­o­gy. On top of that, Metageno­mi’s en­zymes would still need to be paired up with a de­liv­ery sys­tem to get the ther­a­py where it needs to go.

But for now, Metageno­mi will keep plug­ging away in or­der to val­i­date its tech­nol­o­gy. Thomas said that, as a bio­chemist, it’s ex­cit­ing to look at some of these or­gan­isms that have nev­er been seen un­der a mi­cro­scope be­fore that po­ten­tial­ly hold the key to the next cell ther­a­pies.

“Metage­nomics is a very pow­er­ful sci­ence, and I think Metageno­mi is a clear leader in us­ing that sci­ence to de­vel­op and tap in­to this avail­able, nat­ur­al cel­lu­lar ma­chin­ery out there that can be used,” Thomas said. “We’re ex­cit­ed about what na­ture has to of­fer as we dig deep­er in­to this dataset.”

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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Kenneth Galbraith, incoming Zymeworks CEO

Zymeworks re­places half its C-suite, aims to lay off 25% of to­tal work­force as new CEO takes over

New Zymeworks CEO Kenneth Galbraith is aiming to hit the ground running when his tenure officially begins next month, but he’ll be doing so with a much different looking team.

In a lengthy press release outlining the biotech’s 2022 goals, Galbraith said Zymeworks will be laying off at least 25% of its staff over the course of the year. Half of its C-suite will also be replaced immediately as Galbraith looks to remake the company in his image after Ali Tehrani, Zymeworks’ founder and CEO since 2003, stepped down two weeks ago.

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Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Crit­ics push back on Alzheimer’s As­so­ci­a­tion ad blitz to get Medicare to change its Aduhelm rul­ing: 'Dead wrong'

The latest Alzheimer’s Association advertising campaign encourages people to fight.

Not against the disease or for more research or treatments, but against the Centers for Medicare and Medicaid Services. More specifically, CMS’ recent reimbursement decision to only pay for Biogen and Eisai’s controversial Alzheimer’s drug Aduhelm for patients in clinical trials.

With CMS’ preliminary decision now in a 30-day comment period, patient advocates’ goal is to convince CMS to reverse its decision with a marketing blitz and public pressure.

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Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Fail­ing to con­firm clin­i­cal ben­e­fit, Gilead pulls 2 ac­cel­er­at­ed ap­proval in­di­ca­tions for can­cer drug

Gilead recently decided to pull two indications for its cancer drug Zydelig — in relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic leukemia (SLL) — after failing to complete the confirmatory trials required as part of the accelerated approvals from 2014.

“As the treatment landscape for FL and SLL has evolved, enrollment into the confirmatory study has been an ongoing challenge,” Gilead said in a statement, noting it formally notified the FDA of its decision to voluntarily withdraw these indications.

Richard Pazdur (via AACR)

Time lim­its on ac­cel­er­at­ed ap­provals? FDA's on­col­o­gy chief Rick Paz­dur eyes po­ten­tial re­forms via in­ter­na­tion­al ap­proach­es

The spotlight on the accelerated approval pathway continues to shine bright, with the FDA’s top oncology official writing in an opinion that the pathway may be strengthened with bits and pieces of what other regulators in Europe and elsewhere have done with their expedited approval pathways, such as adding expiration dates for these faster approvals to ensure they confirm clinical benefit in a timely manner.

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Covid-19 roundup: HHS may strug­gle to ab­sorb Op­er­a­tion Warp Speed; Eu­rope has no plans for a fourth vac­cine dose

Operation Warp Speed, perhaps the greatest achievement of the former Trump administration, promptly delivered Covid-19 vaccine supplies nationwide when they became available, thanks to collaborations between HHS and the Department of Defense, while helping to fund and aid the manufacture of billions of doses.

But since the Biden administration took over a year ago, acting FDA commissioner Janet Woodcock transitioned out of her role as the therapeutics lead in Warp Speed, which has been converted into a new operation without the fancy name (now known as the “HHS-DOD COVID-19 Countermeasures Acceleration Group”), and as of the start of 2022, the Department of Defense is no longer helping HHS on the program.