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.

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

No­var­tis' sec­ond at­tempt to repli­cate a stun­ning can­cer re­sult falls flat

Novartis’ hopes of turning one of the most surprising trial data points of the last decade into a lung cancer drug has taken another setback.

The Swiss pharma announced Monday that its IL-1 inhibitor canakinumab did not significantly extend the lives or slow the disease progression of patients with previously untreated locally advanced or metastatic non-small cell lung cancer when compared to standard of-care alone.

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Robert Califf (Pablo Martinez Monsivais, AP Images, File)

As buzz on Califf FDA nom heats up, in­dus­try and agency in­sid­ers of­fer a strong nod for the ‘per­fect’ choice

For once in this long, dramatic road to finding a new FDA commissioner, there’s been some continuity. Both CNN and Politico reported this weekend that Rob Califf met with President Biden to discuss the permanent commish role, following earlier news broken by the Washington Post that all signs point to Califf.

Although there may be a few Democrats who continue to grandstand about the dangers of COI (Califf has worked for Verily, sits on the board of Centessa Pharmaceuticals, and has other ties to industry research), with the pandemic ongoing and the need for some kind of continuity at FDA mounting, Califf is likely to meet the same fate as when he first won Senate confirmation in 2016, by a vote of 89-4 — Bernie Sanders and 6 others didn’t vote.

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AstraZeneca CEO Pascal Soriot (Raphael Lafargue/Abaca/Sipa USA)

A com­bo of As­traZeneca's Imfinzi and chemo wins where oth­ers have failed in piv­otal bil­iary tract test

Looking to run with the big dogs in the PD-(L)1 class, AstraZeneca’s Imfinzi has a tall hill to climb to compete in an increasingly bustling market. An aggressive combo strategy for the drug has paid off so far, and now AstraZeneca is adding another notch to its belt.

A combo of Imfinzi (durvalumab) and chemotherapy significantly extended the lives of first-line patients with advanced biliary tract cancer over chemo alone, according to topline results from the Phase III TOPAZ-1 study revealed Monday.

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Sean Ianchulev, Eyenovia CEO and CMO

Re­cent court de­ci­sion push­es FDA to re­ject and re­clas­si­fy drug-de­vice com­bo, crush­ing shares

Back in April, the FDA lost a crucial court case in which its broad discretion of regulating medical products that might satisfy the legal definitions of either “drug” and/or “medical device” was sharply curtailed.

In addition to the appeals court ruling that Genus Medical Technologies’ contrast agent barium sulfate (aka Vanilla SilQ) should not be considered a drug, as the FDA had initially ruled, but as a medical device, the agency also was forced to spell out which drugs would transition to devices as a result of the ruling.

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Peter Greenleaf, Aurinia CEO

Af­ter pass­ing on Ac­celeron, Bris­tol My­ers eyes bolt-on ac­qui­si­tion of au­toim­mune spe­cial­ist — re­port

Bristol Myers Squibb is looking to beef up its autoimmune portfolio by scooping up Aurinia Pharmaceuticals, Bloomberg reported.

The recent overtures to Aurinia, relayed by anonymous insiders, came just as Bristol Myers turned down buyout talks with partners at Acceleron — which Merck ultimately struck a deal to acquire for $11.5 billion. Bristol Myers has reportedly decided to cash out on its minority stake, likely bagging $1.3 billion in the process, while keeping the royalty deals on two of Acceleron’s blood disorder drugs.

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So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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