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.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA chief Stephen Hahn on Capitol Hill earlier this week (Getty Images)

As FDA’s work­load buck­les un­der the strain, Trump again ac­cus­es the agency of a po­lit­i­cal hit job

Peter Marks appeared before a virtual SVB Leerink audience yesterday and said that his staff at FDA’s CBER is on the verge of working around the clock. Manufacturing inspections, policy work and sponsor communications have all been pushed down the to-do list so that they can be responsive to Covid-related interactions. And the agency’s objective right now? “To save as many lives as we can,” Marks said, likening the mortality on the current outbreak as equivalent to “a nuclear bomb on a small city.”

David Berry (Flagship)

Flag­ship's next big tech­no­log­i­cal bet? The cloud

Earlier this month, Flagship announced their big bet on the software half the industry is talking about, launching the AI and machine learning startup. Now, they and a couple other investors are gambling $100 million on a software that much of the public generally thinks of as a cool, IT afterthought: cloud computing.

The idea, says founder and Flagship partner David Berry, is one of scale: The sheer magnitude of biological data that you can store on cloud technology is unprecedented. And that size, when leveraged properly, can allow you to ask questions and form insights that are similarly unprecedented.

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Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

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The win­dow is wide open as four more biotechs join the go-go IPO class of 2020

It’s another day of hauling cash in the biopharma world as four more IPOs priced Friday and a fifth filed its initial paperwork.

The biggest offering comes from PMV Pharma, an oncology biotech focusing on p53 mutations, which raised $211.8 million after pricing shares at $18 apiece. Prelude Therapeutics, developing PRMT5 inhibitors for rare cancers, was next with a $158 million raise, pricing shares at $19 each. Graybug Vision raised $90 million after pricing at $16 per share for its wet AMD candidates, and breast cancer biotech Greenwich Lifesciences brought up the rear with a small, $7 million raise after pricing shares at $5.75.

J&J of­fers PhI/IIa da­ta show­ing its sin­gle-dose vac­cine can stir up suf­fi­cient im­mune re­sponse

Days after J&J dosed the first participants of its Phase III ENSEMBLE trial, the pharma giant has detailed the early-stage data that gave them confidence in a single-dose regimen.

Testing two dose levels either as a single dose or in a two-dose schedule spaced by 56 days in, the scientists from Janssen, the J&J subsidiary developing its vaccine, reported that the low dose induced a similar immune response as the high dose. The interim Phase I/IIa results were posted in a preprint on medRxiv.

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Play-by-play of Gilead­'s $21B Im­munomedics buy­out de­tails a fren­zied push — and mints a new biotech bil­lion­aire

Immunomedics had not really been looking for a buyout when the year began. Excited by its BLA for Trodelvy, submitted to the FDA in late 2019, executive chairman Behzad Aghazadeh started off looking for potential licensing deals and zeroed in on four potential partners, including Gilead, following January’s JP Morgan Healthcare Conference in San Francisco. Such talks advanced throughout the year, with discussions advancing to the second round in mid-August.

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President Donald Trump reacts after signing an executive order following his remarks on his healthcare policies yesterday in Charlotte, North Carolina (Getty Images)

Op-ed: Will phar­ma re­al­ly pay for Trump’s lat­est law­less promise to 33 mil­lion Medicare ben­e­fi­cia­ries? Not like­ly

Sitting atop the executive branch, President Donald Trump is the ultimate authority at the FDA. He can fast track any vaccine to approval himself. If it came to that, of course.

What he can’t do is unilaterally order the legislative branch to loosen the Treasury’s coffers for $6.6 billion. Nor can he command pharmaceutical companies to pay for $200 vouchers sent to 33 million Medicare beneficiaries for prescription drugs before the election.

Pal­la­dio bags $20 mil­lion Se­ries B to top­ple a prob­lem­at­ic kid­ney dis­ease drug

Palladio Biosciences just took one step further in its quest to topple Otsuka’s Samsca with its own — it hopes safer — autosomal dominant polycystic kidney disease (ADPKD) drug.

The Pennsylvania-based biotech announced a $20 million Series B on Friday, which will fund a 10-person Phase III trial of its vasopressin V2 receptor agonist, lixivaptan. CEO Alex Martin expects to read out data in the first half of next year, then launch straight into a larger pivotal Phase III study with about 1,200 participants.