Rosana Kapeller listening to a member on the breakfast panel at #BIO19 discuss AI in R&D in Philadelphia (Jeff Rumans for Endpoints News)

Nim­bus founder Rosana Kapeller has a new com­pa­ny, with $50M and an eye on the ‘re­peatome’

Rosana Kapeller left Nim­bus two years ago de­ter­mined, af­ter 2 decades and 3 com­pa­nies, that her next spot would be as CEO. To­day, af­ter a 7-month sab­bat­i­cal and a stint at a top VC firm, the joc­u­lar com­pu­ta­tion­al bi­ol­o­gy pi­o­neer is back. And with full con­trol.

“I re­al­ly want­ed to… make a unique or­ga­ni­za­tion, a unique cul­ture,” Kapeller told End­points News. I want­ed that chal­lenge.”

And a chal­lenge it will be, both sci­en­tif­i­cal­ly and be­cause, well, there’s a pan­dem­ic keep­ing much of her 10-per­son team work­ing from her home. “This is a hard time to start a com­pa­ny,” she ac­knowl­edged.

Still, Kapeller is con­fi­dent, plac­ing her faith both in the am­bi­tious sci­ence of her new com­pa­ny and in her own ex­pe­ri­ence as a busi­ness­woman, dat­ing back to her up­bring­ing in a busi­ness-fo­cused fam­i­ly in Brazil. The new com­pa­ny is ROME Ther­a­peu­tics and it’s launch­ing out of stealth mode with $50 mil­lion in Se­ries A fund­ing from GV — where Kapeller served as en­tre­pre­neur-in-res­i­dence for the last year — ARCH Ven­tures, and Part­ners In­no­va­tion Fund. The biotech is one of a se­ries that have arisen in the past few years to tar­get parts of what was once deemed “junk DNA”: the 97-99% of ge­net­ic code that doesn’t code for pro­teins. Al­though sci­en­tists have known for decades now that at least parts of this vast nu­cle­ic flot­sam serve key func­tions, un­tan­gling those func­tions has been a ma­jor hur­dle. Drug­ging them has been an even larg­er one.

ROME will tar­get one seg­ment of this erst­while junk called the “re­peatome.” The name has yet to catch on — a PubMed search pro­duced 22 re­sults and the Wikipedia page is a sin­gle para­graph at­trib­uted to one PLOS pa­per out of France — but the field has slow­ly gained steam since a 2011 Sci­ence pa­per, on which ROME co-founder David Ting was lead au­thor.

The re­peatome refers to some 50% of hu­man DNA that is made up of se­quences that re­peat over and over again — like a mu­si­cal or lit­er­ary mo­tif — and that don’t make any pro­teins. Some of these, as sci­en­tists have long known, are retro­virus­es that in­fect­ed us and em­bed­ded their codes in our DNA over mil­lions of years of evo­lu­tions. Oth­er se­quences, though, are “virus-like,” said Ting. Most of the time these se­quences are blocked from do­ing any­thing, trapped by methyl agents or hi­s­tones that wrap like chains around DNA. But in some in­stances — such as some can­cers — dis­tressed cells take the chains off and trans­late the se­quences in­to RNA. Those RNA se­quences don’t make any pro­teins. But they look like RNA virus­es and ac­ti­vate the in­nate im­mune sys­tem as a virus would, call­ing it to at­tack a tu­mor.

“These re­peats are like the first re­spon­ders, telling the body these cells are be­com­ing un­con­trol­lable — con­trol it,” Kapeller said.

Two prob­lems can emerge. First, can­cer cells can de­vel­op ways of re­verse tran­scrib­ing these RNA se­quences back in­to their genome, both si­lenc­ing the im­mune sig­nals and adding to the can­cer’s ge­net­ic vari­abil­i­ty. In some au­toim­mune con­di­tions, the op­po­site prob­lem is at play, Kapeller said. Healthy cells send off these RNA re­peats, trig­ger­ing a dam­ag­ing im­mune re­sponse.

Kapeller talks about ROME’s role as restor­ing “yin and yang”: Keep­ing the im­mune sig­nals go­ing in can­cer and turn­ing them off in au­toim­mune dis­eases. ROME has not yet re­vealed how they plan on do­ing that, but when Ting first hy­poth­e­sized that can­cers were tran­scrib­ing these sig­nals, he start­ed a clin­i­cal tri­al with a com­mon HIV drug on 4th line colon can­cer pa­tients. The HIV drug, which is meant to stop the HIV virus from re­verse tran­scrib­ing it­self, ap­peared to in­hib­it the can­cer’s abil­i­ty to re­verse tran­scribe the RNA sig­nals. The pa­tients on the study main­tained their con­di­tion, a rar­i­ty for that form and stage of can­cer.

“Some­how can­cer has re­pur­posed this process to repli­cate and grow in­to tu­mor,” Ting told End­points, de­scrib­ing his dis­cov­ery. “It was kind of an ac­ci­dent, an ac­ci­dent of some­thing we were told was junk and find­ing the junk was ac­tu­al­ly do­ing some­thing.”

David Ting

Click on the im­age to see the full-sized ver­sion

That some­thing evad­ed sci­en­tists in part be­cause ear­ly DNA se­quencers lacked the abil­i­ty to pick up and an­a­lyze these vast codex­es of DNA and study which re­peats were be­ing tran­scribed in­to RNA. To do so, ROME will re­ly on two new but es­tab­lished tech­niques, se­quenc­ing of long stretch­es of DNA and se­quenc­ing of the RNA be­ing tran­scribed in­side a cell, along­side a ma­chine learn­ing ap­proach set up by the­o­ret­i­cal physi­cist Ben­jamin Green­baum. In part, that’s what made it a fit­ting project for Kapeller, who did com­pu­ta­tion­al work at Mil­len­ni­um and Ailleron and then was en­list­ed by At­las Ven­tures to launch Nim­bus, one of the first ma­jor com­pu­ta­tion­al biotechs.

Al­though it will be Kapeller’s first stint as a CEO, it will hard­ly be her first time in lead­er­ship. Nim­bus lacked a CEO for its first 4.5 years, she notes, leav­ing con­trol of the biotech be­tween her­self and the board. She says that she’s learned a few things from her ex­pe­ri­ence with past com­pa­nies: That con­trol and com­mand doesn’t work, trans­paren­cy is nec­es­sary, and di­ver­si­ty and putting women in man­age­ment mat­ters. She brings an MD-PhD’s un­der­stand­ing of pa­tients, she said, and she took some­thing be­sides busi­ness acu­men back from her home­town of Rio de Janeiro: a cer­tain warmth.

“I’m from Brazil and Brazil­ians love to use hu­mor a lot,” Kapel­lar said.

For in­stance, she led off the com­pa­ny’s first meet­ing with their PR firm with a slide of her­self and her co-founders in Ro­man glad­i­a­tor cos­tumes. She’s re­luc­tant to men­tion those jokes in in­ter­views, though, weary af­ter enough years as an ex­ec­u­tive of how it might be trans­lat­ed.

With the sci­ence, she’s bold­er. They’re one of the first jump­ing in­to a still-emerg­ing field, she said, and their goal is sus­tained re­mis­sion: can­cer and au­toim­mune treat­ments that won’t stop work­ing af­ter a few months, or years.

This is “com­plete­ly un­chart­ed ter­ri­to­ry,” Kapeller said.

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.

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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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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?

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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.

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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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Work taking place in the clean rooms at Vor (Credit: Vor)

Vor Bio opts to keep man­u­fac­tur­ing op­er­a­tions in-house for de­vel­op­ing stem cell, CAR-T ther­a­pies

While it is not uncommon for a biotech to go down the route of having the product manufactured by a contract organization, one small biotech is looking to keep its card close to its chest.

Vor Biopharma has started manufacturing operations at an in-house facility at its HQ in Cambridge, MA after beginning construction last summer.

According to the biotech, the facility aims to develop Vor’s hematopoietic stem cells (eHSCs) and CAR-T therapies for patients with blood cancers. The site will initially manufacture a clinical supply of its candidate VCAR33allo to support its IND, which is slated to be submitted in the first half of next year. It also plans to transfer the production of VOR33 to the facility. Vor is getting to work quickly as engineering runs for VCAR33allo has started this week.

Aim­ing for fourth nod, Sarep­ta files an­oth­er DMD gene ther­a­py to FDA; Ax­some head­ed to­ward mi­graine re­sub­mis­sion

Sarepta Therapeutics has filed the data needed for an FDA accelerated approval, which would be the biotech’s fourth if granted by the agency.

The biotech has yet to complete confirmatory trials for those first three conditional nods. The filing for its fourth Duchenne muscular dystrophy treatment, disclosed Thursday, is not a surprise. Sarepta said in late-July it would do so after releasing positive results for the Roche-partnered gene therapy.