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.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

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WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

Scoop: Gilead ter­mi­nates ear­ly-stage FLT3 tri­al in sol­id tu­mors

Gilead chopped a Phase Ib dose escalation study in recent days, with an update to the federal trials database saying the premature termination followed an “internal safety assessment.”

The IV-administered FLT3 agonist, dubbed GS-3583, was being tested as a monotherapy in 13 patients with advanced solid tumors. The goal of the trial was to find out what dose to test in a Phase II, or maximum tolerated dose.

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Susan Galbraith, AstraZeneca EVP, oncology R&D, at EUBIO22 (Rachel Kiki for Endpoints News)

As­traZeneca’s Su­san Gal­braith high­lights twin wins for the can­cer drug pipeline at SABCS, as oral SERD ex­cels

It’s a good time to be the head of R&D for oncology at AstraZeneca. And no one gets that quite like Susan Galbraith.

Today, Galbraith is at the San Antonio Breast Cancer Symposium, highlighting the data on two key drugs in the cancer pipeline: mid-stage results for its oral SERD camizestrant among patients after one line of therapy, and the AKT drug capivasertib, wrapping the Phase III. Both fall neatly into the range of successes, beating out fulvestrant in hormone receptor-positive, HER2-negative breast cancer.

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