Sci­en­tists find un­ex­pect­ed an­ti-can­cer ac­tiv­i­ty in range of non-on­col­o­gy drugs — study

As the sec­ond lead­ing cause of mor­tal­i­ty glob­al­ly, the lu­cra­tive field of can­cer treat­ment has elicit­ed a fren­zy of drug de­vel­op­ment and bil­lions in ven­ture fund­ing. But a new study sug­gests that can­cer-killing com­pounds may be lurk­ing in the ex­ist­ing ar­se­nal of non-on­col­o­gy med­i­cines.

By an­a­lyz­ing thou­sands of FDA-ap­proved drugs and com­pounds that have been proven safe in clin­i­cal tri­als, sci­en­tists at the Broad In­sti­tute of MIT and Har­vard and Dana-Far­ber Can­cer In­sti­tute found near­ly 50 com­pounds — in­clud­ing drugs for di­a­betes, in­flam­ma­tion, al­co­holism and even a treat­ment for arthri­tis in dogs — with pre­vi­ous­ly un­de­tect­ed an­ti-can­cer ac­tiv­i­ty.

Todd Gol­ub

“We thought we’d be lucky if we found even a sin­gle com­pound with an­ti-can­cer prop­er­ties, but we were sur­prised to find so many,” said Todd Gol­ub, chief sci­en­tif­ic of­fi­cer and di­rec­tor of the Can­cer Pro­gram at the Broad, Charles A. Dana In­ves­ti­ga­tor in Hu­man Can­cer Ge­net­ics at Dana-Far­ber, and pro­fes­sor of pe­di­atrics at Har­vard Med­ical School, in a state­ment.

The study, pub­lished in the jour­nal Na­ture Can­cer, em­ployed the Broad’s Drug Re­pur­pos­ing Hub, an­a­lyz­ing 4,518 drugs against 578 hu­man can­cer cell lines from the Broad’s Can­cer Cell Line En­cy­clo­pe­dia. Af­ter tag­ging each cell line with a DNA bar­code, the re­searchers ex­posed each pool of bar­cod­ed cells to a sin­gle com­pound from the re­pur­pos­ing li­brary and mea­sured the sur­vival rate of can­cer cells.

Some of the can­cer-slay­ing com­pounds kill in un­fore­seen ways, study lead au­thor Steven Corsel­lo said. Corsel­lo is an on­col­o­gist at Dana-Far­ber and founder of the Drug Re­pur­pos­ing Hub.

Most ex­ist­ing can­cer drugs work by sti­fling pro­teins — but some of the can­cer-killing com­pounds Corsel­lo et al came across ap­peared to work by ac­ti­vat­ing a pro­tein or sta­bi­liz­ing a pro­tein-pro­tein in­ter­ac­tion. For ex­am­ple, the team found that near­ly a dozen non-on­col­o­gy drugs killed can­cer cells that ex­press a pro­tein called PDE3A by sta­bi­liz­ing the in­ter­ac­tion be­tween PDE3A and an­oth­er pro­tein called SLFN12.

Steven Corsel­lo

The re­sults of the analy­sis — which scoured near­ly half of all drugs ever test­ed in hu­mans — sug­gests that some non-on­col­o­gy drugs could be tak­en straight in­to clin­i­cal test­ing in can­cer pa­tients, al­though sci­en­tists will need to en­sure the can­cer culling ac­tiv­i­ty of these drugs is ob­served at con­cen­tra­tions that are tol­er­a­ble in hu­mans. It is al­so im­per­a­tive to con­firm that the pre­dic­tive bio­mark­ers iden­ti­fied in cell lines rep­re­sent dis­tinct pop­u­la­tions of hu­man tu­mors, the re­searchers cau­tioned.

“In con­trast to the repo­si­tion­ing of ex­ist­ing drugs for new in­di­ca­tions, the…re­sults re­port­ed here al­so rep­re­sent start­ing points for new drug de­vel­op­ment. In par­tic­u­lar, when the an­ti-can­cer ac­tiv­i­ty of a drug oc­curs via an off-tar­get mech­a­nism, it is like­ly that fur­ther op­ti­miza­tion for this new tar­get will re­sult in more po­tent and se­lec­tive drug can­di­dates,” the re­searchers wrote.

Re­pur­pos­ing drugs on pur­pose (or by ac­ci­dent) has yield­ed some suc­cess — that the process in­volves large­ly de-risked com­pounds, low­er de­vel­op­men­tal costs, and briefer time­lines don’t hurt ei­ther.

Aside from as­pirin’s car­dio­vas­cu­lar ben­e­fits, Vi­a­gra is an­oth­er heav­i­ly cit­ed ex­am­ple. The drug was orig­i­nal­ly be­ing test­ed as a treat­ment for coro­nary hy­per­ten­sion — but a pesky side ef­fect felt by pa­tients in tri­als cul­mi­nat­ed in its even­tu­al ap­proval as an erec­tile dys­func­tion drug.

Then there’s the seda­tive thalido­mide — which gained no­to­ri­ety af­ter its link to se­vere skele­tal birth de­fects trig­gered its with­draw­al in 1957. How­ev­er, years lat­er it was deemed ef­fec­tive as a can­cer treat­ment, even breed­ing the de­vel­op­ment and ap­proval of even more suc­cess­ful de­riv­a­tives, such as Cel­gene’s block­buster Revlim­id.

Mean­while, Mer­ck’s Vioxx — which was un­cer­e­mo­ni­ous­ly tak­en off shelves af­ter its link to dou­bling pa­tients’ risk of heart at­tack and stroke emerged — could resur­face as a gener­ic treat­ment for a side ef­fect ex­pe­ri­enced by he­mo­phil­ia pa­tients.

But akin to tra­di­tion­al drug de­vel­op­ment, drug re­pur­pos­ing has al­so seen its share of set­backs. Two ex­am­ples of late-stage fail­ures in­clude a bid to use the an­ti­his­t­a­mine, la­trepir­dine, as a treat­ment for Hunt­ing­ton’s dis­ease, as well as the pur­suit of re­pur­pos­ing the an­tibi­ot­ic, cef­tri­ax­one, as a med­i­cine for ALS.

Alaa Halawaa, executive director at Mubadala’s US venture group

The ven­ture crew at Mubadala are up­ping their biotech cre­ation game, tak­ing care­ful aim at a new fron­tier in drug de­vel­op­ment

It started with a cup of coffee and a slow burning desire to go early and long in the biotech creation business.

Wrapping up a 15-year discovery stint at Genentech back in the summer of 2021, Rami Hannoush was treated to a caffeine-fueled review of the latest work UCSF’s Jim Wells had been doing on protein degradation — one of the hottest fields in drug development.

“Jim and I have known each other for the past 15 years through Genentech collaborations. We met over coffee, and he was telling me about this concept of the company that he was thinking of,” says Hannoush. “And I got immediately intrigued by it because I knew that this could open up a big space in terms of adding a new modality in drug discovery that is desperately needed in pharma.”

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Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Rohan Palekar, 89bio CEO

89bio’s PhII da­ta add to quick suc­ces­sion of NASH read­outs as field seeks turn­around

89bio said its drug was better than placebo at lessening fibrosis without worsening nonalcoholic steatohepatitis, or NASH, in two of three dose groups.

The San Francisco biotech said it thinks the Phase IIb data pave the way for a potential Phase III, following in the footsteps of another biotech in its drug class, Akero Therapeutics. To fund a late-stage study, CEO Rohan Palekar told Endpoints News 89bio “would need to raise additional capital,” with the company having about $188 million at the end of last year.

FDA in­di­cates will­ing­ness to ap­prove Bio­gen ALS drug de­spite failed PhI­II study

Ahead of Wednesday’s advisory committee hearing to discuss Biogen’s ALS drug tofersen, the FDA appeared open to approving the drug, newly released briefing documents show.

Citing the need for flexibility in a devastating disease like ALS, regulators signaled a willingness to consider greenlighting tofersen based on its effect on a certain protein associated with ALS despite a failed pivotal trial. The documents come after regulatory flexibility was part of the same rationale the agency expressed when approving an ALS drug last September from Amylyx Pharmaceuticals, indicating the FDA’s openness to approving new treatments for the disease.

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Roche and Lil­ly team up to de­vel­op blood test to de­tect ear­ly signs of Alzheimer's

Eli Lilly is teaming up with Roche to help develop a blood test to detect early signs of Alzheimer’s disease and determine whether a patient should go for further confirmatory testing.

Roche’s Elecsys Amyloid Plasma Panel (EAPP) measures pTau 181 protein assay and APOE E4 assay in human blood plasma – elevations in pTau 181 are present in the early stages of Alzheimer’s, while the presence of APO E4 is the most common genetic risk factor for the disease.

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Flare Therapeutics biochemists Yong Li (L) and Valerie Vivat

A $123M Flare will get Third Rock on­col­o­gy biotech in­to the clin­ic this year

Flare Therapeutics will start its first human trial this year with an investigational urothelial cancer drug after pulling together a $123 million Series B from Big Pharmas, VCs and its incubator, Third Rock Ventures.

Launched in 2021 on the idea that a biotech could finally succeed at drugging the much-sought-after but stubborn transcription factor, Flare Therapeutics said Wednesday it is now primed for the clinic after closing its large financing haul earlier this year. The raise is a relatively stark figure in a tough startup financing environment but further buoys the upbeat signals coming out of other Third Rock biotechs in recent weeks, including the $200 million CARGO Therapeutics and $100 million Rapport Therapeutics rounds.

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Francesco Marincola, newly-appointed Sonata Therapeutics CSO

Kite's head of re­search leaves for Flag­ship start­up Sonata

Another leader is departing Kite Pharma, and will to spend the “last part” of his career exploring how cancer evades the immune system.

Kite’s senior VP and global head of cell therapy research Francesco Marincola left the Gilead CAR-T unit last week for Sonata Therapeutics. Flagship last May unveiled the startup, which was pieced together from two fledgling biotechs Inzen and Cygnal Therapeutics. As CSO, Marincola will lead Sonata’s push to reprogram cancer cells to make them more immunogenic.

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Vipin Garg, Altimmune CEO

Al­tim­mune’s shares halved af­ter in­ter­im look at PhII weight loss drug da­ta

Altimmune’s attempt to catch up to Novo Nordisk and Eli Lilly’s GLP-1 drugs hit an investor snag Tuesday after the biotech shared interim Phase II weight loss data.

The Maryland biotech’s pemvidutide is a GLP-1/glucagon dual receptor agonist meant to activate GLP-1 receptors to squash appetite and glucagon to ramp up energy use. The 2.4 mg dose showed a placebo-adjusted weight loss of 9.7% at week 24 of 48, which Jefferies analysts said would be comparable to Novo Nordisk’s semaglutide (Wegovy) and Eli Lilly’s tirzepatide (Mounjaro).

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Josep Bassaganya-Riera, NImmune Biopharma

Ex­clu­sive: Af­ter get­ting his drug back, Lan­dos founder as­sem­bles new start­up for the big PhI­II test

By the time Josep Bassaganya-Riera stepped down as founding CEO of Landos Biopharma in 2021, the company had racked up Phase II data for its top autoimmune program, completed what he called a positive end-of-Phase-II meeting with the FDA and plans to launch pivotal Phase III trials.

Since then, though, the new leaders at Landos have reshuffled their plans for the drug, omilancor, first announcing they will run a Phase IIb ahead of a Phase III and eventually shelving it altogether.

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