Matthew Porteus (Credit: Timothy Archibald for Stanford Children's)

Ver­sant teams up with Stan­ford gene edit­ing ex­perts on a $45M next-gen play — mar­ry­ing CRISPR and AAV to fix sick­le cell

When a re­searchers talk about gene edit­ing, they’re usu­al­ly think­ing about sev­er­al steps. First you need to ze­ro in on the de­fec­tive gene; then, de­pend­ing on the need, you’d want to knock out, re­place or in­sert ge­net­ic ma­te­r­i­al.

CRISPR/Cas9 tech­nolo­gies have trans­formed the field by mak­ing a break­through for the first prob­lem. In­duc­ing dou­ble-strand­ed DNA breaks, or achiev­ing sin­gle-let­ter changes as base edit­ing al­lows, have promis­ing ap­pli­ca­tions in mul­ti­ple dis­eases that are start­ing to get test­ed in hu­mans.

Jer­el Davis

But Ver­sant Ven­tures, one of the pi­o­neer­ing in­vestors in the space, still sees a gap. And they’re team­ing up with a group of promi­nent Stan­ford re­searchers — plus a sea­soned biotech ex­ec — to fill it.

“Achiev­ing high-ef­fi­cien­cy tar­get­ed gene in­te­gra­tion has been a crit­i­cal ob­jec­tive of gene edit­ing for more than 15 years, but on­ly now is this tech­no­log­i­cal­ly pos­si­ble,” Jer­el Davis, Ver­sant’s Van­cou­ver-based man­ag­ing di­rec­tor, said.

Graphite Bio has $45 mil­lion to start things off, but the mon­ey mat­ters lit­tle when com­pared to the rich brain bank it’s draw­ing from.

Matthew Por­teus, an aca­d­e­m­ic founder of CRISPR Ther­a­peu­tics, is lend­ing the tech plat­form to cre­ate this next-gen play along­side gene ther­a­py ex­pert Maria Grazia Ron­car­o­lo.

Draw­ing from re­search work led by Dan­ny De­v­er while a post­doc at Por­teus’ lab, Graphite’s big promise is to in­crease in­te­gra­tion ef­fi­cien­cy from less than 1% to greater than 50% “across di­verse ge­net­ic le­sions in a wide range of cell types.”

Daniel De­v­er

Specif­i­cal­ly, De­v­er and Por­teus showed that they could cor­rect the sick­le β glo­bin gene in pa­tient-de­rived hematopoi­et­ic stem cells ex vi­vo by com­bin­ing Cas9 ri­bonu­cle­o­pro­teins with a donor mol­e­cule that serves as a tem­plate, de­liv­ered in re­com­bi­nant ade­no-as­so­ci­at­ed vi­ral vec­tors of serotype 6 (rAAV6).

That could make for a much more scal­able re­place­ment for trans­plants, they wrote in a 2017 pa­per de­scrib­ing mouse stud­ies.

“No­tably, we de­vise an en­rich­ment par­a­digm to pu­ri­fy a pop­u­la­tion of HSPCs with >90% tar­get­ed in­te­gra­tion,” they wrote. “We al­so show ef­fi­cient cor­rec­tion of the SCD-caus­ing E6V mu­ta­tion in pa­tient-de­rived HSPCs that af­ter dif­fer­en­ti­a­tion in­to ery­thro­cytes, ex­press adult β-glo­bin (HbA) mR­NA, con­firm­ing in­tact tran­scrip­tion­al reg­u­la­tion of edit­ed HBB al­le­les.”

Josh Lehrer

Chief ex­ec­u­tive Josh Lehrer is lead­ing the charge to start Phase I for this pro­gram in ear­ly 2021, bring­ing all the sick­le cell knowl­edge and ex­pe­ri­ence from a six-year run as Glob­al Blood Ther­a­peu­tics, most re­cent­ly as CMO. More pre­clin­i­cal ther­a­pies are in the works for un­named se­ri­ous dis­eases. Sam­sara Bio­Cap­i­tal is join­ing Ver­sant for the launch round and send­ing Abe Bas­san to the board, which al­so fea­tures Davis and Car­lo Riz­zu­to from Ver­sant.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Tom Barnes (Orna)

The mR­NA era is here. MPM be­lieves the fu­ture be­longs to oR­NA — and Big Phar­ma wants a seat at the ta­ble

If the ultra-fast clinical development of Covid-19 vaccines opened the world’s eyes to the promises of messenger RNA, the subsequent delays in supply offered a crash course on the ultra-complex process of producing them. Even before the formulation and fill-finish steps, mRNA is the precious end product from an arduous journey involving enzyme-aided transcription, modification and purification.

For Bristol Myers Squibb, Novartis Institutes for Biomedical Research, Gilead’s Kite and Astellas, it’s time to rethink the way therapeutic RNA is engineered.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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Michael Rome (Foresite)

In search of 'house­hold health­care brands of the fu­ture,' Fore­site Cap­i­tal rais­es $969M to sa­ti­ate a tech-heavy ap­petite

Back in April 2018, just before Foresite Capital unveiled its $668 million Fund IV and a strategy to focus on tech-driven life science bets, one of its portfolio companies quietly made an announcement.

Fount Therapeutics, a drug discovery outfit backed by Foresite and Eshelman Ventures, had raised $22 million in Series A cash to hatch several fledgling spinouts. “The first ‘NewCo,’ Kinnate, will be focused on developing precision oncology treatments,” read a press release.

S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

But it’s not all bad news. Some things are looking up, and there’s still plenty of money to be made in an industry that enjoys a 30% to 40% profit margin, once you factor in steep R&D expenses.

Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

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CEO Fabrice Chouraqui (Cellarity)

Flag­ship up­start Cel­lar­i­ty gath­ers $123M to fi­nance its ex­plo­ration of cell be­hav­ior, blaz­ing a new path to build­ing a broad pipeline

Right from the start, the discovery plan at Flagship-spawned Cellarity was to take their cues from cell biology and follow them to new drugs. Rather than start with a target and develop a drug to hit it, they’d use new technology to digitally map cell behavior and then develop new drugs from what they learned.

“Over the past decades it has always been about finding a target, about reducing a disease to a single molecular target,” says Fabrice Chouraqui, the Novartis vet who was recruited to run the operation about 9 months ago. “And that approach has produced thousands of life-saving medicines. Yet, this approach has limitations. A molecular target approach is fine when you talk about a simple disease, but for very complex diseases like neurodegeneration, like metabolic disease, like cancer, you hope to really harness the complexity of human biology.

Masayoshi Son, SoftBank CEO (glen photo/Shutterstock)

Japan's Soft­Bank plots bil­lions in biotech in­vest­ments in move that could keep the val­u­a­tion flood ris­ing — re­port

The valuation crazy train in biotech continues to roll into the new year with more than a dozen companies taking a chance on Nasdaq and money flowing in from all sides. Now, a Japanese institutional investor is reportedly weighing an entry into the market in a big way — will it keep the bitcoin-esque flood rising?

Already a part-time investor in biotech, SoftBank could drop billions of dollars into the industry as part of helmsman Masayoshi Son’s plan to spend around $80 billion of the firm’s own assets, according to a report from Bloomberg citing people familiar with the plan.

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