Mike Garrett, Flamingo

Io­n­is col­lab­o­ra­tor Flamin­go is ready to take flight with 3 an­ti­sense drugs in the clin­ic and mys­te­ri­ous RNA in its sights

As the biggest name in an­ti­sense tech­nol­o­gy, Io­n­is has long fo­cused on test­ing the in­ter­play be­tween oligonu­cleotides and RNA for ther­a­peu­tic ef­fect. But one class of RNA has most­ly stumped re­searchers — un­til now.

Flamin­go Ther­a­peu­tics of­fi­cial­ly de­buted Thurs­day with three clin­i­cal and one pre­clin­i­cal can­cer drugs hand­ed off from an­ti­sense gu­ru Io­n­is, and an in­trigu­ing if un­proven dis­cov­ery en­gine gun­ning for mys­te­ri­ous long non-cod­ing RNA tar­gets.

It’s not com­mon to see a biotech launch with three clin­i­cal drugs in the fold, but Flamin­go’s short his­to­ry and close re­la­tion­ship with Io­n­is puts it in a unique po­si­tion for suc­cess. The com­pa­ny was found­ed in 2019 with some time in in­cu­ba­tion be­fore that, and it was co-found­ed by the re­search in­sti­tute VIB, Ghent Uni­ver­si­ty, KU Leu­ven, the Uni­ver­si­ty of Michi­gan, Kur­ma Part­ners and PMV.

Chris Mirabel­li

Now, the team is head­ed by CEO Mike Gar­rett and CSO Rob MacLeod, with Io­n­is co-founder Chris Mirabel­li cur­rent­ly serv­ing as chair­man of the board. For Mirabel­li, who left Io­n­is way back in 1993 but was there ear­ly in the an­ti­sense move­ment, Flamin­go rep­re­sents a ma­jor break­through for ASO tech­nol­o­gy and a sign of how the field has come in the past few decades.

“It re­al­ly is a rich area for drug dis­cov­ery and par­tic­u­lar­ly on­col­o­gy,” Mirabel­li told End­points News. “When I got rein­tro­duced to take a look at this par­tic­u­lar com­pa­ny, it was this sort of in­tro­duc­tion to lncR­NAs and my re-in­tro­duc­tion to have far the field had come with oligonu­cleotides and how much each chal­lenge had been met and knocked down. It was the abil­i­ty to get back to my roots.”

The biotech’s lead “Gen 2.5” ASOs tar­get gene tran­scrip­tion fac­tors and what are known as splice-site vari­ants, but the work gets re­al­ly in­ter­est­ing with its on­ly de­clared pre­clin­i­cal can­di­date tar­get­ing MALAT1 — an lncR­NA tar­get Flamin­go thinks could have a big ther­a­peu­tic ben­e­fit in breast can­cer and oth­er tu­mor types. The drug is a prod­uct of re­search out of David Spec­tor’s lab at Cold Spring Har­bor, the fer­tile ground from which Io­n­is and Bio­gen’s Spin­raza sprung.

The mys­te­ri­ous lncR­NA — pro­nounced “link RNA” — is a form of RNA which has a func­tion still lit­tle known to sci­ence. You may re­mem­ber it in its cir­cu­lar form as the back­bone be­hind Flag­ship start­up Laronde, which is aim­ing to de­sign pro­gram­ma­ble “eR­NA” based on the lncR­NA de­sign. But Flamin­go wants to test lncR­NA’s con­nec­tion to can­cer, a still nascent sci­en­tif­ic field but one the biotech be­lieves could of­fer a ma­jor ther­a­peu­tic break­through.

Rob MacLeod

“On­col­o­gy typ­i­cal­ly leads the cut­ting edge be­cause of ac­cess to tu­mor tis­sue and ma­te­ri­als so more is known about lncR­NA in on­col­o­gy than any oth­er ther­a­peu­tic area,” MacLeod told End­points. “More­over, with func­tion­al screens, CRISPR screens and oth­er ways to func­tion­al­ize the genome, it’s be­com­ing clear that there are dri­ver lncR­NAs im­por­tant in cer­tain ma­lig­nan­cies and sub­sets of cer­tain ma­lig­nan­cies.”

The Flamin­go team thinks that an­ti­sense oligonu­cleotides could have a ther­a­peu­tic ef­fect on lncR­NA, once thought to be an un­drug­gable tar­get. So far, the re­sults against MALAT1 are pre­clin­i­cal, but the team thinks those ear­ly da­ta could prove win­ning in hu­mans giv­en ear­ly re­sults show­ing a con­nec­tion be­tween MALAT1 ge­net­ic de­ple­tion and a “dra­mat­ic phe­no­type” in breast can­cer mod­els, MacLeod said.

“We’re go­ing ini­tial­ly in­to breast can­cer, but there are a large num­ber of op­por­tu­ni­ties for MALAT1 through­out on­col­o­gy — it’s been im­pli­cat­ed in many sol­id and hema­to­log­i­cal stud­ies,” MacLeod said. The team ex­pects a po­ten­tial Phase I to start as ear­ly as late 2022.

De­vel­op­ing even more lncR­NA-tar­get­ed drugs is the long-term goal, but the first check­point for Flamin­go will be its three clin­i­cal drugs tar­get­ing STAT-3, An­dro­gen Re­cep­tor (AR) and IRF4 — two tran­scrip­tion fac­tors and a splice-site vari­ant.

Both the STAT-3 and AR can­di­dates have turned out ear­ly hu­man da­ta, and Flamin­go sees a path for­ward in de­vel­op­ing both as per­son­al­ized med­i­cines for pre-se­lect­ed pa­tients as well as pur­su­ing an ag­gres­sive com­bi­na­tion pro­gram with oth­er drugs. In the case of the STAT-3 can­di­date, dubbed dan­vatirsen, the drug has shown some ben­e­fit when part­nered with As­traZeneca PD-1 drug Imfinzi, and the biotech is in­ter­est­ed in team­ing up with oth­er im­mune check­point in­hibitors to test ef­fi­ca­cy.

Mean­while, Flamin­go’s IRF4 can­di­date is just now en­ter­ing hu­man test­ing, and Flamin­go thinks it could be a nat­ur­al com­bo drug as can­cer meds like Revlim­id re­quire IRF4 knock­down to func­tion prop­er­ly.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

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Siddhartha Mukherjee (Brian Ach/Getty Images for The New Yorker)

All Blue's $733M bid to ac­quire Zymeworks turns hos­tile as board bat­tles back — af­ter a biotech celebri­ty jumps in

Yesterday, the team at All Blue Capital — bent on the takeover of a badly battered Zymeworks — brought in celebrated oncologist, Pulitzer prize-winning writer and biotech exec Siddhartha Mukherjee to add some glitz to their proposed board. But they’re still not winning over any converts.

This morning, Zymeworks’ board officially turned this acquisition offer into a hostile showdown, rejecting the unsolicited offer and marshaling its forces to prevent a buyout at $10.50 per share.

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Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Daisy Robinton, Oviva Therapeutics co-founder and CEO

A new spin­out wades in­to ovar­i­an ag­ing, armed with a seed round and ex­per­i­men­tal drugs from Mass Gen­er­al

There aren’t many biotechs emphasizing women’s health, but a new spinout is trying to change that.

Oviva Therapeutics, a pipeline company of New York-based Cambrian Biopharma, emerged from stealth earlier this week to dive into the idea of extending women’s “healthspans,” or what it says is the part of a person’s life spent in generally good health, with a specific focus on ovaries. The emergence comes both with a seed financing worth $11.5 million from Cambrian, and an in-licensing agreement with Massachusetts General Hospital for a trio of patents.

Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

Paul Hudson, Sanofi CEO (via Getty)

Sanofi's $20B buy­out of Gen­zyme pays off again with Eu­ro­pean OK for first Nie­mann-Pick drug

Sanofi CEO Paul Hudson has made clear his intention to develop new rare disease drugs and broaden his company’s offerings. That effort leaped forward on Friday with the EMA’s signing off on the company’s — and the EU’s — first drug to treat the non-central nervous system manifestations of the rare and debilitating Niemann-Pick disease.

The enzyme replacement therapy, developed to replace patients’ deficient or defective enzyme, known as acid sphingomyelinase, was first developed by Genzyme, which Sanofi acquired for more than $20 billion in 2011. That acquisition has also helped Sanofi pull in sales in the field of MS.

Saemundur 'Sam' Oddsson, Sidekick Health co-founder and CMO

Pfiz­er teams up with dig­i­tal ther­a­peu­tics part­ner for next prod­uct launch, this time in atopic der­mati­tis

Big Pharma has been slowly but surely warming up to the potential of digital therapeutics, as evidenced by Sanofi inking a deal two months ago with DarioHealth. And on Thursday, another Big Pharma will take a look at the space in what it deems as simply the next step in an ongoing partnership.

Icelandic biotech Sidekick Health announced the launch of its digital therapeutics product specifically geared for atopic dermatitis Thursday alongside Pfizer, its Big Pharma partner who collaborated on the indication. CMO and co-founder Saemundur “Sam” Oddsson told Endpoints News that this is not the first time that Pfizer and Sidekick Health have worked together — in fact, it is the fourth digital therapeutics product that the pair have co-launched.

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