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.

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.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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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.

Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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Per­cep­tive's fourth — yes, fourth — SPAC jumps to Nas­daq as the blank check tree con­tin­ues to ripen

The biotech SPAC boom has gone almost hand-in-hand with the industry’s IPO gold rush, and this week saw more blank check companies hop aboard the train.

Leading the way is Perceptive Advisors’ fourth SPAC, appropriately named Arya Sciences Acquisition IV, which priced Friday morning after raising $130 million. And on top of that, new Ziopharm executive chair James Huang is launching his own SPAC with MSD Partners and Panacea Venture, filing S-1 paperwork Thursday with plans to raise $200 million.

CEO Fred Aslan (Artiva)

NK cell ther­a­py play­er Arti­va makes some more noise, pulling in $120M Se­ries B less than a month af­ter Mer­ck deal

Not even one month after Big Pharma took notice of Artiva when Merck signed a collaboration worth nearly $2 billion in milestones, the off-the-shelf NK cell biotech already has its next big fundraise.

Artiva returns from the venture well Friday with a $120 million Series B round, money they will use to get their first program into the clinic and to file INDs for another two candidates. The raise marks the latest development in a rapidly expanding footprint for Artiva, which, in addition to the Merck deal last month, has now raised almost $200 million since its Series A last June.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

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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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