Bonnie Berger, MIT professor of mathematics (via MIT)

MIT lab cre­ates tool to find can­cer mu­ta­tion dri­vers 'any­where in the genome'

Pre­ci­sion on­col­o­gy has been her­ald­ed as the way for­ward in treat­ing can­cer, but search­ing for dri­ver mu­ta­tions has com­pli­cat­ed that jour­ney as ex­ist­ing meth­ods can’t be ap­plied to the en­tire genome.

But a new method out of MIT looks to change the way can­cer dri­ver mu­ta­tions are found and, in do­ing so, speed up the process. A group out of Bon­nie Berg­er’s lab at the in­sti­tu­tion has de­vel­oped what they named “Dig,” an in­ter­ac­tive map for find­ing dri­ver el­e­ments and mu­ta­tions “any­where in the genome,” ac­cord­ing to a pa­per pub­lished this week in Na­ture Biotech­nol­o­gy.

The group de­vel­oped a deep learn­ing mod­el by train­ing the AI to map can­cer-spe­cif­ic so­mat­ic mu­ta­tion rates us­ing the Pan-Can­cer Analy­sis of Whole Genomes, or PCAWG, a dataset in­clud­ing 37 can­cer types. The team used high-res­o­lu­tion epi­ge­net­ic as­says from healthy tis­sues to guide the pre­dic­tions.

To dig deep­er, the lab ap­plied Dig to an­oth­er task: find­ing new cod­ing and non-cod­ing can­di­date dri­vers of can­cer us­ing whole-genome, whole-ex­ome and tar­get­ed se­quenc­ing can­cer datasets avail­able to the pub­lic.

Dig ap­peared to beat out many com­pet­ing meth­ods, the group found, not­ing their tool had the high­est mea­sure of ac­cu­ra­cy in 24 out of 32 co­horts in PCAWG. Skin and blood can­cers in PCAWG were ex­clud­ed be­cause of “lo­cal hy­per­mu­ta­tion process­es,” they wrote.

The group’s tool al­so “matched or ex­ceed­ed the per­for­mance” of ex­ist­ing meth­ods used to search ex­cess of mu­ta­tions in dri­ver el­e­ments that had al­ready been iden­ti­fied.

The ac­cu­ra­cy is thanks, in part, to the deep learn­ing tool’s abil­i­ty to find ac­tive tran­scrip­tion start sites and oth­er epi­ge­net­ic struc­tures and then as­so­ciate those struc­tures with the mu­ta­tion rates, the group wrote.

In essence, the com­put­er sci­ence and AI lab led by Berg­er, head of the com­pu­ta­tion and bi­ol­o­gy group, used AI to pre­dict mu­ta­tion rates and com­pared it to re­al da­ta to help train the mod­el to look for mu­ta­tions through­out the genome.

Find­ing dri­ver mu­ta­tions has typ­i­cal­ly been done us­ing ar­bi­trary re­gions of the genome, rather than the broad­er ge­net­ic land­scape, a process that is time-con­sum­ing and ex­pen­sive, the group writes in their pa­per. Pre­vi­ous meth­ods have fo­cused on DNA se­quences that are in­volved in mak­ing pro­teins, like cod­ing and pro­mot­er se­quences, which leave out a big swath of the genome.

“These lim­i­ta­tions con­tribute to cat­a­logs of can­cer dri­ver el­e­ments re­main­ing in­com­plete, par­tic­u­lar­ly in the non-cod­ing genome, hin­der­ing pre­ci­sion on­col­o­gy,” ac­cord­ing to the pa­per.

The group found rare mu­ta­tions re­spon­si­ble for can­cer that oc­cur out­side the al­ready ex­plored re­gions, per­haps shin­ing a light on as much as one-tenth of tu­mors.

“Al­though the dri­ver can­di­dates we re­port — in cryp­tic splice sites, 5′ UTRs and rarely mu­tat­ed genes — oc­curred at low fre­quen­cies in­di­vid­u­al­ly, our es­ti­mates sug­gest that they col­lec­tive­ly con­tribute to the dis­ease pathol­o­gy of up to 10% of tu­mors (sum­ming across the per­cent of tu­mors pre­dict­ed to car­ry ex­cess mu­ta­tions in each of these el­e­ments),” the group wrote in the pa­per.

The team claims the tool can be used quite broad­ly and can churn out re­sults in a mat­ter of min­utes. They have made it pub­licly avail­able.

“Through this frame­work, our maps en­able mil­lions of mu­ta­tions to be eval­u­at­ed in ar­bi­trary can­cer co­horts in min­utes us­ing the re­sources of a per­son­al com­put­er,” the MIT lab wrote in the pa­per.

M&A: a crit­i­cal dri­ver for sus­tain­able top-line growth in health­care

2021 saw a record $600B in healthcare M&A activity. In 2022, there is an anticipated slowdown in activity, however, M&A prospects remain strong in the medium to long-term. What are future growth drivers for the healthcare sector? Where might we see innovations that drive M&A? RBC’s Andrew Callaway, Global Head, Healthcare Investment Banking discusses with Vito Sperduto, Global Co-Head, M&A.

15 LGBTQ lead­ers in bio­phar­ma; Paul Stof­fels’ Gala­pa­gos re­vamp; As­traZeneca catch­es up in AT­TR; 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.

A return to in-person conferences also marks a return to on-the-ground reporting. My colleagues Beth Synder Bulik and Nicole DeFeudis were on-site at Cannes Lions, bringing live coverage of pharma’s presence at the ad festival — accompanied by photos from Clara Bui, our virtual producer, that bring you right to the scene. You can find a recap (and links to all the stories) below.

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David Loew (Ipsen)

Ipsen snags an ap­proved can­cer drug in $247M M&A deal as an­oth­er bat­tered biotech sells cheap

You can add Paris-based Ipsen to the list of discount buyers patrolling the penny stock pack for a cheap M&A deal.

The French biotech, which has had plenty of its own problems to grapple with, has swooped in to buy Epizyme $EPZM for $247 million in cash and a CVR with milestones attached to it. Epizyme shareholders, who had to suffer through a painfully soft launch of their EZH2a inhibitor cancer drug Tazverik, will get $1.45 per share along with a $1 CVR tied to achieving $250 million in sales from the drug over four consecutive quarters as well as an OK for second-line follicular lymphoma by 1 Jan. 2028.

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AstraZeneca's new Evusheld direct to consumer campaign aims to reach more immunocompromised patients.

As­traZeneca de­buts first con­sumer cam­paign for its Covid-19 pro­phy­lac­tic Evusheld — and a first for EUA drugs

AstraZeneca’s first consumer ad for Evusheld is also a first for drugs that have been granted emergency use authorizations during the pandemic.

The first DTC ad for a medicine under emergency approval, the Evusheld campaign launching this week aims to raise awareness among immunocompromised patients — and spur more use.

Evusheld nabbed emergency authorization in December, however, despite millions of immunocompromised people looking for a solution and now more widespread availability of the drug.

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GSK says its drug for chron­ic hep B could ‘lead to a func­tion­al cure’ — but will it be alone or in com­bi­na­tion?

GSK, newly branded and soon-to-be demerged, shared interim results from its Phase II trial on its chronic hepatitis B treatment, one that it says has the “potential to lead to a functional cure.”

At a presentation at the EASL International Liver Congress, GSK shared that in around 450 patients who received its hep B drug bepirovirsen for 24 weeks, just under 30% had hepatitis B surface antigen and viral DNA levels that were too low to detect.

De­spite a slow start to the year for deals, PwC pre­dicts a flur­ry of ac­tiv­i­ty com­ing up

Despite whispers of a busy year for M&A, deal activity in the pharma space is actually down 30% on a semi-annualized basis, according to PwC’s latest report on deal activity. But don’t rule out larger deals in the second half of the year, the consultants said.

PwC pharmaceutical and life sciences consulting solutions leader Glenn Hunzinger expects to see Big Pharma companies picking up earlier stage companies to try and fill pipeline gaps ahead of a slew of big patent cliffs. Though a bear market continues to maul the biotech sector, Hunzinger said recent deals indicate that pharma companies are still paying above current trading prices.

Abortion-rights protesters regroup and protest following Supreme Court's decision to overturn Roe v. Wade. (AP Photo/Gemunu Amarasinghe)

Fol­low­ing SCO­TUS de­ci­sion to over­turn abor­tion pro­tec­tions, AG Gar­land says states can't ban the abor­tion pill

Following the Supreme Court’s historic decision on Friday to overturn Americans’ constitutional right to an abortion after almost 50 years, Attorney General Merrick Garland sought to somewhat reassure women that states will not be able to ban the prescription drug sometimes used for abortions.

Following the decision, the New England Journal of Medicine also published an editorial strongly condemning the reversal, saying it “serves American families poorly, putting their health, safety, finances, and futures at risk.”

Joe Wiley, Amryt Pharma CEO

Am­ryt Phar­ma sub­mits a for­mal dis­pute res­o­lu­tion to the FDA over re­ject­ed skin dis­ease drug

The story of Amryt Pharma’s candidate for the genetic skin condition epidermolysis bullosa, or EB, will soon enter another chapter.

After the Irish drugmaker’s candidate, dubbed Oleogel-S10 and marketed as Filsuvez, was handed a CRL earlier this year, the company announced in a press release that it plans to submit a formal dispute resolution request for the company’s NDA for Oleogel-S10.

Sen. Thom Tillis (R-NC) (J. Scott Applewhite/AP Images)

Phar­ma-friend­ly sen­a­tor calls on FDA for a third time to show patent pro­tec­tions should­n't be blamed for high drug prices

North Carolina Republican Sen. Thom Tillis made a name for himself in the 2020 election cycle as the darling of the pharma industry, accepting hundreds of thousands in campaign contributions, even from the likes of Pfizer CEO Albert Bourla.

Those contributions have led Tillis to attempt to re-write patent laws in pharma’s favor, a move which failed to gain steam in 2019, and request for a third time since January that the FDA should help stop “the false narrative that patent protections are to blame for high drug prices.”