Sekar Kathiresan (Verve)

Look­ing to leapfrog an­ti­bod­ies and RNAi, Sekar Kathire­san says gene edit­ing ap­proach to cut PC­SK9 looks durable

JP Mor­gan isn’t typ­i­cal­ly a da­ta con­fer­ence. But there are al­ways ex­cep­tions for da­ta that could make or break a com­pa­ny, piquing the in­ter­est of po­ten­tial in­vestors and part­ners alike.

Da­ta, for in­stance, like what Sekar Kathire­san is bring­ing to the vir­tu­al con­fer­ence, show­ing that a one-time treat­ment with Verve Ther­a­peu­tics’ base ed­i­tor can keep PC­SK9 lev­els low — there­by low­er­ing LDL cho­les­terol, aka the bad kind — out to 6 months. In non-hu­man pri­mates.

The two take­away fig­ures are 61% LDL cho­les­terol re­duc­tion and 89% cut in av­er­age blood PC­SK9 pro­tein lev­el. That’s the same lev­el of re­duc­tion for PC­SK9 as the treat­ment reg­is­tered at 2 weeks, when the re­searchers doc­u­ment­ed a 59% drop in LDL-C.

“What you are see­ing is durable low­er­ing of cho­les­terol and con­sis­tent low­er­ing of LDL cho­les­terol 6 months af­ter ad­min­is­tra­tion of the gene edit­ing treat­ment,” Kathire­san told End­points News in a pre­view.

While pre­clin­i­cal, the re­sults mark a sig­nif­i­cant step for the in vi­vo use of the next-gen­er­a­tion gene edit­ing tool known as base edit­ing. Where­as the first gen­er­a­tion of CRISPR gene edit­ing mol­e­cules would snip the DNA se­quence and let it re­pair on its own, base edit­ing works by con­vert­ing one let­ter on the genome to an­oth­er.

In this case the con­struct, VERVE-101, made a sin­gle change from A to G in the ge­net­ic se­quence of the PC­SK9 gene in the liv­er, with an aim to in­ac­ti­vate the gene for good.

As liv­er cells turn over rough­ly every 200 days, Kathire­san added, 6-month dura­bil­i­ty da­ta of­fer rea­son­able con­fi­dence that the changes are there to stay.

“The fun­da­men­tal prob­lem with coro­nary heart dis­ease is cu­mu­la­tive ex­po­sure to LDL over time, OK? And the fun­da­men­tal treat­ment is to low­er that cu­mu­la­tive ex­po­sure as much as pos­si­ble,” said the CEO, who left be­hind an aca­d­e­m­ic ca­reer and a di­rec­tor­ship at Mass Gen­er­al’s Cen­ter for Ge­nom­ic Med­i­cine to steer the biotech. “The way to think about this is kind of the area un­der the curve analy­sis, you know? You want to keep the LDL down and con­sis­tent­ly down for as long a pe­ri­od as pos­si­ble.”

VERVE-101 rides on the phar­ma­co­log­ic val­i­da­tion of­fered by mon­o­clon­al an­ti­bod­ies and siR­NA ther­a­pies that tar­get PC­SK9 but does away with the need for chron­ic treat­ment. Each of which he sees pre­sent­ing its own com­pli­ance is­sues that could lead to in­suf­fi­cient pro­tec­tion.

With tox­i­col­o­gy stud­ies un­der­way, Verve ex­pects to dose its first pa­tient some time in 2022. By tar­get­ing the ini­tial clin­i­cal in­di­ca­tion of het­erozy­gous fa­mil­ial hy­per­c­ho­les­terolemia, the com­pa­ny will be de­vel­op­ing “a ge­net­ic treat­ment for a ge­net­ic dis­ease” be­fore turn­ing to “gar­den va­ri­ety coro­nary heart dis­ease.”

PC­SK9 will just be a start. Kathire­san has iden­ti­fied sev­en oth­er genes that, as he’s dis­cov­ered over years of stud­ies in pop­u­la­tion ge­net­ics, har­bor pro­tec­tive mu­ta­tions — one of them be­ing ANGPTL3, for which Verve has al­so pre­sent­ed 2-week pre­clin­i­cal da­ta. All eight tar­gets fall in­to one of three path­ways: LDL-C, triglyc­erides or lipopro­tein(a).

“Each of those path­ways are kind of com­ple­men­tary in terms of risk for a pa­tient,” he said. “So a med­i­cine tar­get­ing each of those path­ways should be ad­di­tive in terms of ben­e­fit.”

Qual­i­ty Con­trol in Cell and Gene Ther­a­py – What’s Re­al­ly at Stake?

In early 2021, Bluebird Bio was forced to suspend clinical trials of its gene therapy for sickle cell disease after two patients in the trial developed cancer. As company scientists rushed to assess whether there was any causal link between the therapy and the cancer cases, Bluebird’s stock value plummeted – as did those of multiple other biopharma companies developing similar therapies.

While investigations concluded that the gene therapy was unlikely to have caused cancer, investors and the public may be more skittish regarding the safety of gene and cell therapies after this episode. This recent example highlights how delicate the fields of cell and gene therapy remain today, even as they show great promise.

JP Gabriel, Ocugen

JP Gabriel watched from the bleach­ers as the pan­dem­ic raged. Now head of sup­ply chain at Ocu­gen, he's ready to bat

The world was in the middle of the most pressing public health risk his generation had ever seen, and JP Gabriel felt like he was sitting on the sidelines. As a VP of biologics and mRNA manufacturing at Ultragenyx, Gabriel watched from the sidelines as players like Pfizer/BioNTech and Moderna used mRNA tech to chase their own Covid-19 vaccines.

This month, Gabriel got the chance to get his hands dirty against the pandemic — but it won’t be with mRNA.

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Sen. Patty Murray (D-WA) (Graeme Sloan/Sipa USA/Sipa via AP Images)

Sen­a­tors to NIH: Do more to pro­tect US bio­med­ical re­search from for­eign in­flu­ence

Although Thursday’s Senate health committee hearing was focused on how foreign countries and adversaries might be trying to steal or negatively influence biomedical research in the US, the only country mentioned by the senators and expert witnesses was China.

Committee chair Patty Murray (D-WA) made clear in her opening remarks that the US cannot “let the few instances of bad actors” overshadow the hard work of the many immigrant researchers in the US, many of which have won Nobel prizes for their work. But she also said, “There is more the NIH can be doing here.”

Law pro­fes­sors call for FDA to dis­close all safe­ty and ef­fi­ca­cy da­ta for drugs

Back in early 2018 when Scott Gottlieb led the FDA, there was a moment when the agency seemed poised to release redacted complete response letters and other previously undisclosed data. But that initiative never gained steam.

Now, a growing chorus of researchers are finding that a dearth of public data on clinical trials and pharmaceuticals means industry and the FDA cannot be held accountable, two law professors from Yale and New York University write in an article published Wednesday in the California Law Review.

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Novavax CEO Stanley Erck at the White House in 2020 (Andrew Harnik, AP Images)

As fears mount over J&J and As­traZeneca, No­vavax en­ters a shaky spot­light

As concerns rise around the J&J and AstraZeneca vaccines, global attention is increasingly turning to the little, 33-year-old, productless, bankruptcy-flirting biotech that could: Novavax.

In the now 16-month race to develop and deploy Covid-19 vaccines, Novavax has at times seemed like the pandemic’s most unsuspecting frontrunner and at times like an overhyped also-ran. Although they started the pandemic with only enough cash to last 6 months, they leveraged old connections and believers into $2 billion and emerged last summer with data experts said surpassed Pfizer and Moderna. They unveiled plans to quickly scale to 2 billion doses. Then they couldn’t even make enough material to run their US trial and watched four other companies beat them to the finish line.

FDA of­fers scathing re­view of Emer­gent plan­t's san­i­tary con­di­tions, em­ploy­ee train­ing af­ter halt­ing pro­duc­tion

The FDA wrapped up its inspection of Emergent’s troubled vaccine manufacturing plant in Baltimore on Tuesday, after halting production there on Monday. By Wednesday morning, the agency already released a series of scathing observations on the cross contamination, sanitary issues and lack of staff training that caused the contract manufacturer to dispose of millions of AstraZeneca and J&J vaccine doses.

Brad Bolzon (Versant)

Ver­sant pulls the wraps off of near­ly $1B in 3 new funds out to build the next fleet of biotech star­tups. And this new gen­er­a­tion is built for speed

Brad Bolzon has an apology to offer by way of introducing a set of 3 new funds that together pack a $950 million wallop in new biotech creation and growth.

“I want to apologize,” says the Versant chairman and managing partner, laughing a little in the intro, “that we don’t have anything fancy or flashy to tell you about our new fund. Same team, around the same amount of capital, same investment strategy. If it ain’t broke, don’t fix it.”

But then there’s the flip side, where everything has changed. Or at least speeded into a relative blur. Here’s Bolzon:

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Covid-19 man­u­fac­tur­ing roundup: Mary­land looks to grow biotech ca­pac­i­ty with $400M check; Rus­sia lands sec­ond Sput­nik V part­ner this week

A Maryland real estate project has added three new biotech-focused manufacturing and research buildings to an office park to keep up with demand created by the pandemic, the Washington Business Journal reported.

The Milestone Business Park — located off of I-270 in Germantown, MD — will see the new buildings and a total of 532,000 square feet as the campus rebrands to Milestone Innovation Park.

Jenny Rooke (Genoa Ventures)

Ear­ly Zymer­gen in­vestor Jen­ny Rooke re­flects on 'chimeras' in biotech, what it takes to spot a $500M gem

When Jenny Rooke first heard of Zymergen back in 2014, she knew she was looking at something different and exciting. The Emeryville, CA biotech held the promise of blending biology and technology to solve a huge unmet need for cost-effective chemicals — of all things — and a stellar founding team to boot.

But back then, West Coast venture capitalists didn’t see in Zymergen the one thing they were looking for in a winning biotech: therapeutic potential. Rooke, however, saw an opportunity and made her bets. Seven years later, that bet is paying off in a big way.

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