Michael Davidson, NewAmsterdam CEO

A much-hyped CV drug failed, re­peat­ed­ly. Now, in­vestors are bet­ting near­ly $200M on one last PhI­II bid

Just un­der a decade ago, Eli Lil­ly an­nounced ear­ly re­sults for a new drug that low­ered bad cho­les­terol and raised good cho­les­terol. It was a “holy grail” re­sult, as JA­MA put it in a press re­lease, of­fer­ing a path for a pill that could curb car­dio­vas­cu­lar dis­ease, still the lead­ing cause of death in the US. Mer­ck, Am­gen, Roche, and Pfiz­er all jumped in with sim­i­lar mol­e­cules.

And then, be­gin­ning in 2015, it all fell apart. The mol­e­cules, known as CETP in­hibitor, boost­ed good cho­les­terol but piv­otal study af­ter piv­otal study showed they didn’t pre­vent heart at­tacks, strokes or oth­er car­dio­vas­cu­lar deaths. “CETP in­hibitor class fi­nal­ly dies,” ran one 2017 head­line, when Mer­ck aban­doned its ef­fort.

Now a group of in­vestors has de­cid­ed to make one last large bid at res­ur­rect­ing the field. The lengthy syn­di­cate, led by Morn­ing­side Ven­tures and For­bion, has put $196 mil­lion in­to a Se­ries A for NewAms­ter­dam Phar­ma, a small Dutch start­up that will take Am­gen’s old mol­e­cule and push it in­to Phase III lat­er this year.

The new ef­fort cen­ters around one of the on­ly CETP block­ers that didn’t make it in­to piv­otal stud­ies. In 2015, months be­fore Lil­ly’s drug bombed, Am­gen paid $300 mil­lion up­front and over a bil­lion in mile­stones to ac­quire Dez­i­ma and its CETP in­hibitor obice­trapib. By 2016, they had sus­pend­ed in­vest­ment. They put it on the shelf the fol­low­ing year, af­ter Mer­ck waived the white flag.

John Kastelein

The new com­pa­ny is led by CSO John Kastelein, one of the sci­en­tists who worked on the orig­i­nal obice­trapib tri­als, and CEO Michael David­son, who served as CSO of Cor­vidia Ther­a­peu­tics be­fore No­vo Nordisk bought out the car­dio-fo­cused com­pa­ny for up­front $725 mil­lion last June.

The two will have to prove that their mol­e­cule can work where sim­i­lar ef­forts have re­peat­ed­ly failed.

David­son, though, says they have good ev­i­dence for their ap­proach. Mer­ck’s CETP in­hibitor ac­tu­al­ly suc­ced­ed in Phase III, but didn’t pro­vide enough ben­e­fit for the com­pa­ny to file for ap­proval. Yet new long-term da­ta sug­gest that, over time, the drug’s ben­e­fit in­creased from a 9% rel­a­tive risk re­duc­tion in pre­vent­ing car­diac events to a 20% risk re­duc­tion.

And he says new ge­nom­ic da­ta sug­gest that re­searchers mis­un­der­stood the drug’s mech­a­nism: In­ves­ti­ga­tors orig­i­nal­ly thought that CETP in­hibitors were ben­e­fi­cial be­cause they boost­ed good cho­les­terol, HDL, by in­cred­i­bly high amounts, but they now think that it’s the mod­est re­duc­tion to bad cho­les­terol, LDL, that dri­ves ben­e­fit.

That means you should be tar­get­ing the drug in tri­als to pa­tients with high lev­els of LDL, David­son said, which the Big Phar­mas didn’t do.

“It’s not CETP in­hi­bi­tion that was the prob­lem,” David­son told End­points News. “It’s the ways drugs were used.”

He al­so point­ed to ev­i­dence from ear­ly stud­ies that their mol­e­cule was bet­ter at low­er­ing LDL than oth­ers, with few­er side ef­fects. They’ll now get a chance to prove it, with sig­nif­i­cant fund­ing to push the drug in­to the no­to­ri­ous­ly large and ex­pen­sive tri­als that car­dio­vas­cu­lar tri­als re­quire. They plan to start those at the end of 2021. They will like­ly take about two years.

“We have the right drug,” David­son said. “We have a safe drug.”

Kaiser Foun­da­tion Hos­pi­tals, BVF Part­ners L.P., Pop­u­la­tion Health Part­ners, LSP De­men­tia Fund, Pe­ter Thiel, Janus Hen­der­son In­vestors, Med­pace, GL Cap­i­tal, JVC In­vest­ment Part­ners, and Pre­sight Cap­i­tal round­ed out the syn­di­cate.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Hal Barron, GSK via YouTube

What does $29B buy you in Big Phar­ma? In Glax­o­SmithK­line’s case, a whole lot of un­com­fort­able ques­tions about the pipeline

Talk about your bad timing.

A little over a week ago, GSK R&D chief Hal Barron marked his third anniversary at the research helm by taking a turn at the virtual podium during JP Morgan to make the case that he and his team had built a valuable late-stage pipeline capable of churning out more than 10 blockbusters in the next 5 years.

And then, just days later, one of the cancer drugs he bet big on as a top prospect — bintrafusp, partnered with Merck KGaA — failed its first pivotal test in non-small cell lung cancer.

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Matt Gline (L) and Vivek Ramaswamy

Scoop: Vivek Ra­maswamy is hand­ing the CEO job to a top lieu­tenant at Roivant — but he’s not ex­act­ly leav­ing the biotech scene

Over the past 7 years since founding Roivant, Vivek Ramaswamy has been a constant blur of biotech building motion.

He launched his first biotech with an Alzheimer’s drug he picked up cheap, and watched the experiment implode in one of the highest profile pivotal disasters seen in the last decade. But it didn’t slow the 30-something exec down; if anything, he hit the accelerator. Ramaswamy blazed global paths and went on to raise billions to spur the creation of a large lineup of little Vants promising big things at a fast pace. He sold off a section of the Vant brigade to Sumitomo Dainippon for $3 billion. And more recently the relentless dealmaker has been building a computational discovery arm to add an AI-driven approach to kicking up new programs and companies, supplementing the in-licensing drive while pursuing advances that have created more than 700 jobs at Roivant, with $2 billion in reserves.

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José Baselga, AstraZeneca cancer chief (Brent N. Clarke/FilmMagic via Getty Images)

As­traZeneca's Calquence nabs an­oth­er win against Im­bru­vi­ca, but Eli Lil­ly is on its heels

Three years after first launching Calquence as a second generation BTK inhibitor, AstraZeneca continues to tout new data to compete with J&J and AbbVie’s first generation blockbuster Imbruvica.

The British pharma announced on Monday that Calquence passed a head-to-head Phase III study against Imbruvica in chronic lymphocytic leukemia, proving non-inferior — i.e. just as good — as the older drug. Although AstraZeneca did not break down any of the numbers, they said the drug proved superior on safety, triggering fewer cases of atrial fibrillation, an irregular heartbeat that can lead to stroke or heart failure.

Ron Cooper, Albireo CEO

Al­bireo just ad­vanced down to the 10-yard line at the FDA. And Ron Coop­er’s team is get­ting prepped for the next big play

When Albireo Pharma’s board $ALBO moved to bring in Ron Cooper as the CEO more than 5 years ago, the development-stage company went with an experienced commercial player who had a big-time position on his resume after running Bristol Myers’ commercial ops in Europe.

Now, after successfully navigating a pivotal study, putting them in a foot race with a rival toward an FDA OK, Cooper is getting a boost from regulators on the last drive back to an arena he understands completely.

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Roche amps up its bis­pe­cif­ic at­tack on Eylea with more PhI­II da­ta — but just how threat­en­ing is it?

Roche has another stack of data to back up its longer-acting challenger to Eylea — although it’s still far from certain just how much they can threaten Regeneron’s dominance.

The latest Phase III results come from two trials that enrolled 1,329 patients with neovascular age-related macular degeneration. With 45% of people in both studies getting faricimab 16 weeks apart during the first year, the bispecific still induced the same level of gains in visual acuity as Eylea every 8 weeks did, Roche’s Genentech reported.

Can strug­gling Iterum turn the cor­ner to an an­tibi­ot­ic suc­cess sto­ry? They will know in six months

More than five years after Corey Fishman and Michael Dunne dusted sulopenem off Pfizer’s shelves — the second castoff antibiotic they’ve brought out of the pharma giant — and founded Iterum Therapeutics around that single drug, they have lined up a quick shot at approval with priority review from the FDA.

The decision, six months from now, will mark a make-or-break moment for a struggling biotech that has just enough cash to keep the lights on until the third quarter.

Bahija Jallal, Immunocore

Buried in Im­muno­core's IPO fil­ings? A kick­back scheme from a now for­mer em­ploy­ee

Immunocore spent much of 2019 dealing with the fallout of the Neil Woodford scandal, as the former star investor’s fall crashed the biotech’s valuation out of unicorn range. Now it turns out that the company spent 2020 dealing with another internal scandal.

The longtime UK biotech darling disclosed in their IPO filing last week that they had fallen victim to an alleged kickback scheme involving one of their employees. After a whistleblower came forward, they said in their F-1, they spent the summer and spring investigating, finding fraud on the part of an employee and two outside vendors.