Rajesh Devraj, Rectify Pharmaceuticals CEO

At­las backs a long­time Ver­tex em­ploy­ee’s quest to bring CF suc­cess to nu­mer­ous oth­er dis­eases

One of Ver­tex’s longest-tenured em­ploy­ees be­lieves he can take the biotech’s biggest med­ical and sci­en­tif­ic ac­com­plish­ments and use it to de­vel­op treat­ments for more than just cys­tic fi­bro­sis.

Three years ago, Jonathan Moore, a sci­en­tist and then ex­ec­u­tive at Ver­tex from 1990 to 2018, found­ed a com­pa­ny to de­vel­op treat­ments for dis­eases that, like CF, are caused by mu­ta­tions in a “su­per fam­i­ly” of pro­teins known as ABC trans­porters.

Jonathan Moore

He’s since man­aged to con­vince a few in­vestors. On Thurs­day, Moore, At­las Ven­ture and a hand­ful of oth­er blue-chip funds de­buted Rec­ti­fy Phar­ma­ceu­ti­cals, backed with $100 mil­lion in Se­ries A funds to find small mol­e­cules that can cor­rect such mu­ta­tions in a broad suite of ge­net­ic dis­or­ders. They’ll start in the liv­er, but even­tu­al­ly plan to hit dis­eases in near­ly every or­gan in the body.

“These are ex­pressed in all dif­fer­ent or­gans, liv­er, lungs, brain, and they play an im­por­tant role in the body,” CEO Ra­jesh De­vraj told End­points News. “You can imag­ine the amount of tar­gets that are avail­able and de­liv­ered for us to go af­ter.”

The new com­pa­ny builds off Ver­tex’s suc­cess in de­vel­op­ing a type of drug that es­sen­tial­ly had nev­er been built be­fore, a small mol­e­cule that can take a mu­tant, dys­func­tion­al pro­tein and morph it back in­to a func­tion­al one.

That work, con­ceived of and fund­ed in part by the CF Foun­da­tion, ul­ti­mate­ly led to four it­er­a­tions of mol­e­cules and com­bi­na­tions of mol­e­cules that over a decade turned one of the most com­mon ge­net­ic dis­eases from a like­ly death sen­tence in­to a treat­able con­di­tion for most pa­tients.

The pro­tein be­hind CF, known as CFTR, is not unique, though. It’s a trans­port pro­tein, shep­herd­ing salts in­to and out of cells. And the con­stant­ly whirling, busy, huffy place that is the hu­man body has many such trans­port pro­teins — 48 to be ex­act. Ac­cord­ing­ly, hu­mankind has many dis­eases as­so­ci­at­ed with mu­ta­tions in those pro­teins.

There are nu­mer­ous ben­e­fits to go­ing af­ter this class of dis­ease, De­vraj points out: They are mono­genic and re­searchers can be cer­tain that, if they suc­cess­ful­ly cor­rect the pro­tein, they can slow or re­verse the dis­ease; and it’s been done be­fore, in­clud­ing by Rec­ti­fy’s founder.

Small mol­e­cules are al­so eas­i­er to de­vel­op, make and de­liv­er than gene ther­a­py or oth­er bi­o­log­ic drugs, es­pe­cial­ly for rare dis­eases that of­ten get over­looked by drug de­vel­op­ers.

“We are — I think we are the foun­da­tion,” De­vraj said. “We are the lead­ers in ABC trans­porter bi­ol­o­gy.”

But there are al­so key hur­dles. Al­though Ver­tex proved that one could de­vel­op a small mol­e­cule to trans­form a mu­tant pro­tein, no one has yet done it suc­cess­ful­ly for any oth­er dis­ease. The big biotech has had its own trou­bles ap­ply­ing the strat­e­gy to a new con­di­tion.

Among the biggest chal­lenges with these dis­eases, De­vraj ac­knowl­edged, is that of­ten dif­fer­ent pa­tients with a sin­gle dis­ease have dif­fer­ent ge­net­ic mu­ta­tions. Like words, genes can be mis­pelled in any num­ber of ways.

That means Rec­ti­fy will po­ten­tial­ly need dif­fer­ent drugs or dif­fer­ent com­bi­na­tions of drugs to fix all or most of the mu­ta­tions in a giv­en dis­ease. It took Ver­tex a decade to find the right tri­ad of mol­e­cules that work for 90% of pa­tients’ CF and it could be even hard­er, both sci­en­tif­i­cal­ly and eco­nom­i­cal­ly, to do the same for dis­or­ders that are even more rare — as the ones Rec­ti­fy pur­sues will al­most cer­tain­ly be.

To over­come those chal­lenges, Rec­ti­fy is ap­ply­ing some of the same tricks Ver­tex did, in­clud­ing de­vel­op­ing tests that, in the­o­ry, could al­low them to quick­ly tell in a lab whether a mol­e­cule is hav­ing its in­tend­ed ef­fect and restor­ing ship­ping lanes in­to and out of cells. De­vraj said they have al­ready de­vel­oped the first as­says but de­clined to de­scribe them.

The com­pa­ny is keep­ing its in­di­ca­tions undis­closed for now, too, ex­cept that they will start in the liv­er, be­fore hope­ful­ly ex­pand­ing to the lung and cen­tral ner­vous sys­tem. The cur­rent fi­nanc­ing, co-led by Omega, For­bion and Long­wood, should get them through proof-of-con­cept clin­i­cal tri­als for the first mol­e­cule.

“Noth­ing is go­ing to be easy,” De­vraj said. That’s “why we do this job.”

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

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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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty


I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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Luc Boblet, Egle Therapeutics CEO

A new Treg play­er emerges with $46M and back­ing from Take­da

In recent years, the chorus of biotechs and Big Pharma backers targeting regulatory T cells — also known as “Tregs” — for cancer and autoimmune diseases has only grown louder.

The newest voice is from Egle Therapeutics, which sang out a $46.4 million Series A round on Friday led by LSP and Bpifrance through their InnoBio 2 fund. Takeda’s venture arm also chipped in, about a year after the pharma struck a research pact with the Paris-based upstart.

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René Russo, Xilio CEO (Alicia Petitti for Xilio)

Xilio Ther­a­peu­tics goes pub­lic as bio­phar­ma IPOs rum­ble for­ward in Q4

It’s been a busy fall on Wall Street — and this week, we’ve got another biotech going public after Ventyx yesterday.

Massachusetts solid-tumor biotech Xilio Therapeutics made its public debut today, joining 149 other biotechs that have gone public so far this year.

Back on October 1st, Xilio filed its S-1 with the SEC to make its IPO debut for $100 million — the next step in financing after completing a $95 million Series C back in February.