Peter Ghoroghchian, Ceptur CEO

A new start­up wants to take an­ti­sense and siR­NA one step fur­ther, and build more po­tent drugs than Io­n­is and Al­ny­lam

Drug­ging RNA has be­come a hot bio­phar­ma top­ic in re­cent years, par­tic­u­lar­ly af­ter the mas­sive suc­cess­es of the Covid-19 vac­cines. But one biotech is aim­ing to take things a step fur­ther, uti­liz­ing the sin­gle-strand­ed mol­e­cules be­fore they even be­come RNA.

Cep­tur Ther­a­peu­tics launched Wednes­day morn­ing with a $75 mil­lion Se­ries A, the com­pa­ny an­nounced. The goal is to push for­ward a slate of oligonu­cleotide-based ther­a­pies that can con­trol gene ex­pres­sion, and even si­lence some tar­get­ed genes, at the “pre-mR­NA lev­el,” co-founder and CEO Pe­ter Ghoroghchi­an told End­points News.

The biotech has re­cruit­ed a blue-chip syn­di­cate as well, with ven­Bio and Qim­ing Ven­tures co-lead­ing the round. In ad­di­tion, Cep­tur re­ceived new sup­port from Per­cep­tive Xon­toge­ny Ven­ture Fund, Bris­tol My­ers Squibb and Janus Hen­der­son In­vestors.

Cep­tur’s main idea cen­ters around a pro­tein com­plex known as the U1 snRNP (pro­nounced SNURP), which Ghoroghchi­an said serves as a bi­o­log­i­cal gate­keep­er when DNA is tran­scribed in­to RNA and RNA in­to pro­teins. When cells go through this process, they’re con­stant­ly splic­ing ge­net­ic se­quences in and out, with some left out of the fi­nal mR­NA.

“The splic­ing ma­chin­ery that helps mR­NA to ma­ture is re­cruit­ed by the U1 snRNP, and the U1 snRNP al­so helps to turn off and con­trol the lev­el of tran­scripts, so how much of a giv­en mR­NA is made,” Ghoroghchi­an said. “It does this for every sin­gle gene in the body, so it has this very cen­tral role in bi­ol­o­gy.”

To take ad­van­tage of these gate­ways and cre­ate drugs, re­searchers led by Rut­gers pro­fes­sor Sam Gun­der­son, an­oth­er Cep­tur co-founder, de­vel­oped bi­va­lent oligonu­cleotides called U1 Adap­tors. The adap­tors tar­get spe­cif­ic ge­net­ic se­quences and re­cruit the U1 snRNP to de­stroy the de­sired pre-mR­NA, es­sen­tial­ly con­trol­ling which genes make it in­to the fi­nal pro­teins.

It’s an ap­proach sim­i­lar to an­ti­sense oligonu­cleotides and siR­NA ther­a­pies, Ghoroghchi­an said, on­ly Cep­tur aims to drug the RNA at a much more gran­u­lar lev­el. And be­cause the U1 snRNP is so ubiq­ui­tous through­out the body — Ghoroghchi­an says there are more than one mil­lion copies in every cell — Cep­tur be­lieves dif­fer­ent cell types and genes won’t im­pede the com­pa­ny’s progress.

Col­in Walsh

Col­in Walsh, a part­ner at Qim­ing Ven­tures, not­ed the RNA drug­ging field has boomed in re­cent years, ever since the idea took off in the ear­ly days of Io­n­is and Al­ny­lam. But he be­lieves Cep­tur rep­re­sents a big step for­ward in how such ap­proach­es will shape the space in the fu­ture, par­tic­u­lar­ly once it moves past the gene si­lenc­ing ap­pli­ca­tion.

“There is a large ap­petite for ways to con­trol pro­tein func­tion at the RNA lev­el,” Walsh said. “The U1 Adap­tor pro­tein com­plex is re­al­ly a mas­ter reg­u­la­tor of the tran­scrip­tome, it’s splic­ing and oth­er things. Though knock­down is the first place where you can take this, we see this as a re­al­ly broad po­ten­tial plat­form for mod­u­lat­ing RNA us­ing oli­go-based ther­a­peu­tics.”

For its in-house pipeline, Cep­tur isn’t re­veal­ing much just yet. Ghoroghchi­an said the team has a few can­di­dates that could hit IND-en­abling stud­ies some­time in 2023, in­clud­ing on­col­o­gy pro­grams tar­get­ing KRAS and MYC in can­cer, as well as one for Hunt­ing­ton’s dis­ease. Past that, though, every­thing re­mains in the dis­cov­ery phase.

And though the biotech is try­ing to con­trol ge­net­ic se­quenc­ing, Ghoroghchi­an be­lieves Cep­tur’s drugs will prove far safer than gene ther­a­pies that some­times con­tin­ue edit­ing DNA be­yond the ther­a­peu­tic use. Be­cause Cep­tur isn’t en­gag­ing in DNA or base edit­ing, its drugs will on­ly work as long as the adap­tor is in the pa­tient’s sys­tem.

Cep­tur’s oligonu­cleotides are ex­treme­ly small, Ghoroghchi­an said, and “every nu­cleotide is chem­i­cal­ly mod­i­fied. And we can use a lot of ex­ist­ing and val­i­dat­ed chemistries to di­al in how long it lasts, ei­ther to how long they can knock the gene down, or how quick­ly it can be de­grad­ed, in or­der to di­al in the safe­ty as­pect.”

On top of the new in­vestors, Cep­tur al­so re­ceived Se­ries A sup­port from ex­ist­ing seed in­vestors Affin­i­ty As­set Ad­vi­sors, Box­er Cap­i­tal and LifeSci Ven­ture Part­ners.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Ivan Cheung, Eisai US chairman and CEO

Bio­gen, Ei­sai re­fresh amy­loid hy­poth­e­sis with PhI­II show­ing Alzheimer's med slows cog­ni­tive de­cline

In the first look at Phase III data for lecanemab, Eisai and Biogen’s follow-up Alzheimer’s drug to the embattled Aduhelm launch, results show the drug passed with flying colors on a test looking at memory, problem solving and other dementia metrics.

One of the most-watched Alzheimer’s therapies in the clinic, lecanemab met the study’s primary goal on the CDR-SB — Clinical Dementia Rating-Sum of Boxes — giving the biotech the confidence to ask for full approval in the US, EU and Japan by next March 31. The experimental drug reduced clinical decline on the scale by 27% compared to placebo at 18 months, the companies said Tuesday night Eastern time and Wednesday morning in Japan.

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Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

BREAK­ING: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Some­one old, some­one new: Mod­er­na pro­motes CTO, raids No­var­tis for re­place­ment amid pipeline push

Moderna CEO Stéphane Bancel made clear on the last quarterly call that “now is not the time to slow down.” On Thursday, he made a bit more room in the cockpit.

The company unveiled a new executive role on Thursday, promoting former chief technical operations and quality officer Juan Andres to president of strategic partnerships and enterprise expansion, and poaching a former Novartis exec to take his place.

Gilead names 'k­ing­pin­s' in coun­ter­feit HIV med law­suit

Gilead is mounting its counterfeit drug lawsuit, naming two “kingpins” and a complex network of conspirators who allegedly sold imitation bottles of its HIV meds, some of which ended up in US pharmacies.

The pharma giant on Wednesday provided an update on what it called a “large-scale, sophisticated counterfeiting conspiracy,” accusing two new defendants of “leading and orchestrating” a scheme to sell hundreds of millions of dollars in illegitimate drugs posing as meds such as Biktarvy and Descovy.

Vlad Coric, Biohaven CEO (Photo Credit: Andrew Venditti)

As Amy­lyx de­ci­sion waits in the wings, Bio­haven’s ALS drug sinks (again) in plat­form tri­al

The FDA’s decision on Amylyx’s ALS drug is set to come out sometime Thursday. In a space with few drugs, any approval would be a major landmark.

But elsewhere in the ALS field, things are a bit more tepid.

Thursday morning, Biohaven announced that its drug verdiperstat failed its arm of an ALS platform trial led by Massachusetts General Hospital. According to a press release, the drug did not meet its primary endpoint — improvement on an ALS functional status test — or any key secondary endpoints at 24 weeks. The trial had enrolled 167 patients, giving them either verdiperstat or placebo twice a day.

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Tar­sus looks to raise aware­ness of eye­lid mite dis­ease in cam­paign aimed at eye­care spe­cial­ists

Eyelid mite disease may be “gross” but it’s also fairly common, affecting about 25 million people in the US.

Called demodex blepharitis, it’s a well-known condition among eyecare professionals, but they often don’t always realize how common it is. Tarsus Pharmaceuticals wants to change that with a new awareness campaign called “Look at the Lids.”

The campaign and website debut Thursday — just three weeks after Tarsus filed for FDA approval for a drug that treats the disease.

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Marcelo Bigal, Ventus Therapeutics CEO

No­vo Nordisk joins No­var­tis, Roche in NL­RP3 are­na, bet­ting $70M cash on NASH, car­diometa­bol­ic us­es

As a drug target, the NLRP3 inflammasome has drawn serious interest from Big Pharma, inspiring a series of M&A deals from Novartis and Roche on top of venture investments by others. Now Novo Nordisk is jumping on the bandwagon — and the Danish pharma giant is taking the target where it knows best.

Novo Nordisk is getting its NLRP3 inhibitors from Ventus Therapeutics, a Versant-backed startup that set out to make some of the best NLRP3 drugs out there by incorporating new insights into the structure of the target complex.

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