Jennifer Pietenpol (Joe Howell for Vanderbilt)

Back to the draw­ing board for triple-neg­a­tive breast can­cer tar­gets, re­searchers pro­pose new com­bo ap­proach

The rea­son why triple-neg­a­tive breast can­cer is such a tough dis­ease to treat is large­ly giv­en away in its name. Such tu­mors can’t be de­fined by tra­di­tion­al bio­mark­ers — nei­ther es­tro­gen re­cep­tors, prog­es­terone re­cep­tors, nor ex­cess HER2 pro­tein — forc­ing drug hunters down un­chart­ed new path­ways.

Re­searchers at Van­der­bilt-In­gram Can­cer Cen­ter ex­plored one of them, and turned up with some new sug­ges­tions.

Jo­han­na Schafer

In a new pa­per, the sci­en­tists be­gan with the ob­ser­va­tion that dereg­u­lat­ed MY­CN — a mem­ber of the tran­scrip­tion fac­tor fam­i­ly that ac­ti­vates ex­pres­sion of some onco­genes — has been im­pli­cat­ed in a sub­set of breast can­cers with un­fa­vor­able prog­nos­tic fea­tures and clin­i­cal out­comes. They end­ed by putting forth a new drug reg­i­men that could spark new hope.

“Giv­en that pa­tients with TNBC pri­mar­i­ly re­ceive sys­temic cy­to­tox­ic chemother­a­pies that fre­quent­ly re­sult in un­fa­vor­able out­comes,” they wrote in Sci­ence Trans­la­tion­al Med­i­cine, “we pro­pose the clin­i­cal de­vel­op­ment of com­bi­na­tion BETi and ME­Ki for pa­tients with ad­vanced TNBC, with par­al­lel eval­u­a­tion of MY­CN as a po­ten­tial mark­er for pa­tient se­lec­tion.”

Jo­han­na Schafer, a grad­u­ate stu­dent work­ing in Jen­nifer Pieten­pol’s lab, is the first au­thor, while the pro­fes­sor is the se­nior au­thor.

The MY­CN pro­tein, some­times dubbed N-Myc, has long been stud­ied as a tar­get in neu­ronal or neu­roen­docrine tu­mors, but its role in breast can­cer is less clear. It’s dis­tinct from MYC (c-Myc), though the two are be­lieved to af­fect each oth­er.

Their in­tri­cate re­la­tion­ship would prove cru­cial in ther­a­peu­tic de­vel­op­ment. But the first ques­tion is just how com­mon they are, and ac­cord­ing to the study, the two fam­i­ly mem­bers are “het­ero­ge­neous­ly ex­pressed in sep­a­rate cell nu­clei with­in a giv­en tu­mor in at least 40% of TNBC tu­mors.” In fact, the ex­pres­sion of MY­CN ap­peared to in­crease af­ter neoad­ju­vant chemother­a­py, part of the cur­rent stan­dard of care.

The preva­lence gave them enough rea­son to think about how to tar­get it. When the team se­lect­ed a cell line mod­el, they had an­oth­er find­ing that MY­CN-ex­press­ing cells were es­sen­tial­ly more prone to re­sis­tance to PI3K in­hibitors, which block an al­ter­na­tive path­way for tu­mor growth.

Be­cause the MYC fam­i­ly lack cat­alyt­ic do­mains, the team re­sort­ed to epi­ge­net­ic reg­u­la­tors, screen­ing 158 com­pounds against the cell lines. BET drugs, which block the bro­mod­omain (BRD)-con­tain­ing fam­i­ly of tran­scrip­tion­al reg­u­la­tors, emerged as the win­ner.

It echoes an ear­li­er study, done at Michi­gan State Uni­ver­si­ty, show­ing that the ex­per­i­men­tal class of mol­e­cules can pre­vent the growth of breast and lung can­cers.

But that’s not it — and here’s where the MEK in­hibitors come in.

Most of the MYNC-ex­press­ing TNBCs al­so con­tain MYC-ex­press­ing cells, the re­searchers not­ed, which can still dri­ve can­cer growth. In fact, sin­gle-agent treat­ment with a BETi seemed to have in­creased MYC ex­pres­sion. Adding tram­e­tinib (Mekin­ist) to the cells, how­ev­er, de­creased the amount of both pro­teins. The re­sults were fur­ther test­ed and con­firmed in mouse mod­els.

“As a next step, our re­search team is propos­ing the fur­ther de­vel­op­ment and clin­i­cal tri­als of this com­bi­na­tion ther­a­py,” Pieten­pol, the di­rec­tor of Van­der­bilt-In­gram and EVP for re­search at Van­der­bilt Uni­ver­si­ty Med­ical Cen­ter, said in a state­ment.

In­cyte, which has a pact in place to fund Van­der­bilt re­search such as this study, has a BET in­hibitor in ear­ly de­vel­op­ment.

Why it Works: Man­u­fac­tur­ing a Vac­cine in a Mul­ti-Prod­uct Fa­cil­i­ty.

COVID-19 launched the pharmaceutical industry to the frontline in the battle against the fast-spreading global pandemic. The goal: distribute a safe, effective vaccine as quickly as possible. Major players in the vaccine market needed to partner with contract development and manufacturing organizations (CDMOs) to achieve the goal of mass vaccine quantities under expedited timelines. With CDMOs stepping up to play a critical role in the vaccine manufacturing process, multi-product CDMO facilities took the spotlight. Partnerships quickly formed as the race to save lives and fight a pandemic was on.

Merck CEO Rob Davis

Mer­ck emerges as lead bid­der in po­ten­tial Ac­celeron buy­out with deal pos­si­ble this week — re­port

With rumors swirling about a potential buyout of biotech Acceleron and its lead PAH drug sotatercept, market watchers have been keeping close tabs on industry movers and shakers due up for an expensive bolt-on. According to a new report, it appears Merck may be the one.

Merck is in “advanced talks” on a deal to acquire Cambridge, MA-based Acceleron in what previous reports pegged as a potential $11 billion buyout, the Wall Street Journal reported Monday. A deal could come as early as this week, according to the Journal.

Alexander Lefterov/Endpoints News

The coro­n­avirus vac­cine that the world for­got could still help save it

Back at the beginning of the pandemic — back when we still called the virus “novel” and a single case in Washington state could make headlines — there emerged the story of the coronavirus vaccine that the world forgot.

It was an allegory for our pandemic ill-preparedness. At a time when the world had been caught so flat-footed, there were a pair of scientists who had seen the crisis coming, lab-coated Cassandras with an antidote if only the world had listened sooner.

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Habib Dable, Acceleron CEO

Days of heat­ed ru­mors cul­mi­nate in a re­port that Ac­celeron is in ad­vanced buy­out talks

Days of frothy rumors about possible M&A discussions at Acceleron were capped late Friday with a Bloomberg report asserting that the biotech company is in advanced talks for an $11 billion buyout deal.

Bloomberg was unable to identify any bidders in the deal, but speculation has been running rampant that the surging value of Acceleron stock had to be the result of leaks around the auction of the company. As of early Monday morning, we’re still awaiting the final word.

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Anthony Fauci, NIAID director (AP Images)

NIH spot­lights trio of aca­d­e­m­ic teams chas­ing af­ter 'pan-coro­n­avirus' vac­cines

Having made loud and clear its call for new research on vaccines that can tackle future pandemics, the NIH is shedding light on some of the projects it’s funding.

The National Institute of Allergy and Infectious Diseases (NIAID) has awarded around $36.3 million to three academic groups that are working on developing “pan-coronavirus vaccines” — inoculations that can protect against a diverse family of coronaviruses, especially the voracious ones like SARS-CoV-2.

Safe­ty fears force Pfiz­er to change piv­otal DMD gene ther­a­py tri­al pro­to­col

As one of the biggest players in an increasingly packed gene therapy space, Pfizer has taken an early lead over specialists like Sarepta in taking a Duchenne muscular dystrophy (DMD) candidate into late-stage testing. But new safety fears have led Pfizer to scale back that trial, cutting out patients with certain genetic mutations.

Pfizer has amended its enrollment protocol for a Phase III test for gene therapy fordadistrogene movaparvovec in DMD after investigators flagged severe side effects tied to specific mutations, according to a letter the drugmaker sent to Parent Project Muscular Dystrophy, a patient advocacy group.

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Albert Bourla, Pfizer CEO (John Thys, Pool via AP Images)

Covid-19 roundup: Pfiz­er/BioN­Tech sub­mit vac­cine da­ta to FDA for younger chil­dren; Doc­tors kept pre­scrib­ing hy­drox­y­chloro­quine

Pfizer and BioNTech said Tuesday they submitted to FDA positive data from a Phase II/III trial of their Covid-19 vaccine in children aged 5 to less than 12 years old.

A formal EUA submission for the vaccine in these children is expected to follow “in the coming weeks,” the companies said in a statement.

The trial of 2,268 healthy participants aged 5 to less than 12 years old showed the vaccine was safe and elicited robust neutralizing antibody responses using a two-dose regimen of 10 μg doses, which is one-third the dose that’s administered to adults.

From left to right: Mark Springel, Kristina Wang, Lin Ao, Soufiane Aboulhouda

George Church, his stu­dents, and top VCs go na­tion­wide with a biotech train­ing camp

One night last fall, Floris Engelhardt sat down in her Boston apartment and logged onto a Zoom call, armed with a comic and a vague idea about starting a biotech.

Engelhardt was joining a student-run “match night.” A postdoc at MIT’s Bathe BioNanoLab, where researchers use DNA and RNA like Lego blocks for nanometer-sized structures, Engelhardt wanted to find real-world applications for her work. She sketched out — literally — a plan to use DNA origami, a decade-old technique for precisely folding DNA, to make therapies.

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Paul Hudson, Sanofi CEO (Cyril Marcilhacy/Bloomberg via Getty Images)

Sanofi calls it quits on mR­NA Covid-19 shots, scrap­ping vac­cine from $3.2B Trans­late Bio buy­out

Sanofi is throwing in the towel on mRNA-based Covid-19 vaccines.

The French drugmaker will halt development on its unmodified mRNA Covid-19 shot despite what it said were positive Phase I/II results, a spokesperson told Endpoints News on Tuesday morning. Sanofi said the reason it’s stopping the Covid-19 mRNA program, developed in partnership with its new $3.2 billion acquisition Translate Bio, is because the market is too crowded.