John Leonard, Intellia CEO

Search­ing for CRISPR 2.0, In­tel­lia spends $45M cash on an un­known Berke­ley spin­out

Even as two of the first gen­er­a­tion of CRISPR com­pa­nies have shown pow­er­ful re­sults in the clin­ic, they’ve faced a grow­ing threat: new tech­nolo­gies such as base and prime edit­ing that can con­duct more ver­sa­tile and po­ten­tial­ly safer edit­ing.

In­tel­lia, which last year be­came the first com­pa­ny to show CRISPR can work di­rect­ly in pa­tients, is hop­ing that a lit­tle-known start­up can help it stay on the cut­ting edge. On Thurs­day it an­nounced a buy­out of a tiny and ef­fec­tive­ly un­known Berke­ley spin­out called Rewrite Ther­a­peu­tics for $45 mil­lion cash and $155 mil­lion in mile­stones that In­tel­lia claims can do a host of ge­net­ic ed­its cur­rent­ly lim­it­ed to prime edit­ing and a cou­ple oth­er tech­nolo­gies.

“At In­tel­lia, we have built the in­dus­try’s broad­est and deep­est genome edit­ing plat­form by stay­ing at the fore­front of new tech­niques, while al­so ex­tend­ing the ca­pa­bil­i­ties of CRISPR/Cas9 edit­ing to make pre­cise­ly tar­get­ed changes to DNA,” CEO John Leonard said in a state­ment. Rewrite of­fers In­tel­lia “new pos­si­bil­i­ties and the po­ten­tial to tar­get dis­eases be­yond those cur­rent­ly be­ing ex­plored in our pipeline.”

Shahram Seyedin-Noor, head of Civ­i­liza­tion Ven­tures — the VC that seed­ed Rewrite — claimed the com­pa­ny is a “kind of CRISPR 2.0,” the same moniker of­ten ap­plied to base and prime edit­ing but with po­ten­tial im­prove­ments on both.

That’s no small boast: Prime edit­ing caused a me­dia fren­zy when Har­vard pro­fes­sor David Liu and his post­doc An­drew An­za­lone pub­lished it in Oc­to­ber 2019. A hand­ful of blue-chip VCs poured $315 mil­lion in­to a new start­up fo­cused on turn­ing the tech in­to ther­a­pies.

Prime al­lowed re­searchers to ma­nip­u­late DNA in ways no oth­er sys­tem had: chang­ing any let­ter of DNA in­to any oth­er and mak­ing com­plex changes, such as large in­ser­tions and dele­tion.

It is al­so a com­plex and un­wieldy sys­tem, dif­fi­cult to work with and dif­fi­cult to fit in­side the vi­ral vec­tors some­times used to de­liv­er oth­er CRISPR sys­tems. (Al­though im­prove­ments are be­ing made.)

Shahram Seyedin-Noor

Seyedin-Noor claims Rewrite’s tech­nol­o­gy al­lows it to be snuck in­side a vi­ral vec­tor or lipid nanopar­ti­cle, al­though he didn’t elab­o­rate on how. His­tor­i­cal­ly, re­searchers have some­times fit CRISPR sys­tems in­to vi­ral vec­tors, by break­ing it apart and putting it in­to two dif­fer­ent vec­tors, but that tends to make the sys­tem less ef­fi­cient.

It can al­so, they say, work in non-di­vid­ing cells such as those in the ner­vous sys­tem, where Seyedin Noor said can be dif­fi­cult to get prime edit­ing to work.

“That’s pret­ty large,” said Seyedin-Noor. It “adds a whole area of ther­a­peu­tics that’s un­touched right now.”

Liu’s lab, how­ev­er, did show ef­fi­ca­cy in neu­rons in their orig­i­nal 2019 pa­per. In a Na­ture Gene Ther­a­py re­view of the field last year, two re­searchers, Ja­nine Schofield and Patrick T. Har­ri­son, not­ed prime edit­ing was par­tic­u­lar­ly im­por­tant be­cause it showed pre­cise ge­net­ic sub­sta­tions in non-di­vid­ing cells, “al­beit at low fre­quen­cy.”

And for now, Rewrite’s claims are just that. Un­like Prime, Rewrite Ther­a­peu­tics’ tech­nol­o­gy re­mains un­pub­lished.

Its founders, how­ev­er, have re­leased ear­li­er it­er­a­tions of the work, al­beit for an en­tire­ly dif­fer­ent ap­pli­ca­tion.

Shakked Halperin

In 2018, Rewrite co-founder and CEO Shakked Halperin and his then-ad­vi­sor David Schaf­fer pub­lished in Na­ture a CRISPR-based sys­tem that al­lowed re­searchers to tar­get a 750-let­ter stretch in the genome and in­tro­duce se­mi-ran­dom mu­ta­tions at that spot. At the time, though, they demon­strat­ed it not as a way to ed­it genes in pa­tients but to has­ten and re­fine di­rect­ed evo­lu­tion — a No­bel Prize-win­ning tech­nique for con­duct­ing ba­sic re­search and for de­sign­ing use­ful pro­teins.

In­tel­lia was qui­et about how it would use the tech­nol­o­gy, but they’ve long hint­ed at plans be­yond Cas9. Al­though their head­line-grab­bing amy­loi­do­sis tri­al last year and the rest of their list­ed pipeline us­es clas­sic Cas9, they’ve al­so be­gun de­sign­ing and pub­licly pre­sent­ing base ed­i­tors.

No word yet on how they’ll use those, ei­ther.

The ar­ti­cle has been up­dat­ed to clar­i­fy lan­guage on dif­fer­ence be­tween rewrite’s tech­nol­o­gy and prime edit­ing. 

Susan Galbraith, AstraZeneca EVP, oncology R&D, at EUBIO22 (Rachel Kiki for Endpoints News)

Up­dat­ed: As­traZeneca jumps deep­er in­to cell ther­a­py 2.0 space with $320M biotech M&A

Right from the start, the execs at Neogene had some lofty goals in mind when they decided to try their hand at a cell therapy that could tackle solid tumors.

Its founders have helped hone a new approach that would pack in multiple neoantigen targets to create a personalized TCR treatment that would not just make the leap from blood to solid tumors, but do it with durability. And they managed to make their way rapidly to the clinic, unveiling their first Phase I program for advanced tumors just last May.

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Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

Twit­ter dis­ar­ray con­tin­ues as phar­ma ad­ver­tis­ers ex­tend paus­es and look around for op­tions, but keep tweet­ing

Pharma advertisers on Twitter are done — at least for now. Ad spending among the previous top spenders flattened even further last week, according to the latest data from ad tracker Pathmatics, amid ongoing turmoil after billionaire boss Elon Musk’s takeover now one month ago.

Among 18 top advertisers tracked for Endpoints News, only two are spending: GSK and Bayer. GSK spending for the full week through Sunday was minimal at just under $1,900. Meanwhile, German drugmaker Bayer remains the industry outlier upping its spending to $499,000 last week from $480,000 the previous week. Bayer’s spending also marks a big increase from a month ago and before the Musk takeover, when it spent $16,000 per week.

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Vi­a­tris with­draws ac­cel­er­at­ed ap­proval for top­i­cal an­timi­cro­bial 24 years lat­er

After 24 years without confirming clinical benefit, the FDA announced Tuesday morning that Viatris (formed via Mylan and Pfizer’s Upjohn) has decided to withdraw a topical antimicrobial agent, Sulfamylon (mafenide acetate), after the company said conducting a confirmatory study was not feasible.

Sulfamylon first won FDA’s accelerated nod in 1998 as a topical burn treatment, with the FDA noting that last December, Mylan told the agency that it wasn’t running the trial.

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Catal­ent to cut about 200 jobs in Mary­land and Texas

Contract manufacturing company Catalent is cutting about 200 jobs in Maryland and Texas, according to WARN notices, trimming back some of its pandemic-era expansion.

The company will cut 77 jobs by Jan. 15 of next year at a cell therapy facility in Webster, TX, just outside of Houston. In Maryland, the company is reducing staff at two locations, with 82 jobs being eliminated at Catalent’s facility in Gaithersburg, and 53 in Rockville. The layoffs go into effect at those locations on Jan. 14.

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Bris­tol My­ers scraps gene ther­a­py deal with uniQure for car­dio­vas­cu­lar dis­eases

Bristol Myers Squibb is hitting the exit on a collaboration with a gene therapy biotech.

The Big Pharma company will no longer partner with uniQure on finding new treatments for cardiovascular diseases, the biotech reported to the SEC last week, following a rocky relationship that saw the pair break off an earlier agreement — before coming back to the table. The deal will officially terminate on Feb. 21, 2023.

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iECURE CEO Joe Truitt and founder Jim Wilson

Jim Wil­son biotech iECURE gets fresh $65M to push pe­di­atric liv­er dis­ease gene ther­a­py in­to the clin­ic

Jim Wilson-founded biotech iECURE has wrapped a $65M Series A extension round to get its lead candidate — a gene replacement therapy for a rare inherited liver disease known as ornithine transcarbamylase deficiency, or OTC — into the clinic.

This round was co-led by Novo Holdings and LYFE Capital, followed by initial investors Versant and OrbiMed as well. In September 2021, iECURE raised a $50 million Series A led by the latter two. The new cash infusion will get iECURE through an initial in-human trial, which CEO Joe Truitt told Endpoints News iECURE hopes to read out in 2024.

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Tim Walbert, Horizon Therapeutics CEO (via YouTube)

Hori­zon Ther­a­peu­tics in takeover talks with Am­gen, J&J, Sanofi as po­ten­tial buy­ers

Amgen, J&J’s Janssen and Sanofi are all in talks to acquire Horizon Therapeutics, the rare disease biotech disclosed late Tuesday.

Horizon confirmed “highly preliminary discussions” with those companies regarding a potential buyout offer after the Wall Street Journal reported takeover interest.

Although the company — which commands a market cap of close to $18 billion — emphasized that “there can be no certainty that any offer will be made for the Company,” shares $HZNP still surged 31% in after-hours trading to near $103, bringing it to the point where it started the year.

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Sana, Codex­is lay off staff, reshuf­fle pipeline in bid to fo­cus cell ther­a­py, en­zyme en­gi­neer­ing work

As its market cap shrinks to a fraction of its heyday, flashy cell therapy startup Sana Biotechnology is laying off 15% of its staffers in a move to rejig the pipeline and restructure the company.

Sana is among a growing group of biotechs that, feeling the weight of a broader market downturn and seeing their shares tumble steadily, are tightening the purse strings and adjusting their focus. Also on Tuesday, Codexis, an enzyme engineering company based in California and now helmed by former Sierra Oncology CEO Stephen Dilly, announced it will reduce the workforce by 18%.

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