Mark Gold­smith Rev­o­lu­tion

Gilead is jump­ing on board the pro­tein degra­da­tion band­wag­on. And they’re turn­ing to a low-pro­file Third Rock start­up for the ex­per­tise. But if you were look­ing for a trans­for­ma­tion­al deal to kick up fresh en­thu­si­asm for Gilead, you’ll have to re­main pa­tient.

This one will have a long way to go be­fore they get in­to the clin­ic.

The big biotech said Wednes­day morn­ing that it is pay­ing $45 mil­lion up­front and re­serv­ing a whop­ping $2.3 bil­lion in biotech bucks if San Fran­cis­co-based Nurix can point the way to new can­cer ther­a­pies, as well as drugs for oth­er, un­spec­i­fied dis­eases.

John McHutchi­son Gilead

Still in the pre­clin­i­cal phase 5 years af­ter Mark Gold­smith — dis­patched by Third Rock to launch West Coast biotechs and now CEO at Rev­o­lu­tion — boot­ed up the com­pa­ny with an un­usu­al­ly lean $25 mil­lion ven­ture round, Nurix quick­ly picked up an im­pres­sive $150 mil­lion up­front from a new deal back in 2015 with the then pro­lif­ic Cel­gene. It has 2 pre­clin­i­cal ef­forts un­der­way, one in house and a CDL-B pro­gram paired with Cel­gene, which will soon mi­grate to Bris­tol-My­ers Squibb.

Gilead CSO John McHutchi­son counts him­self as an ad­mir­er of Nurix’s tech plat­form, hop­ing it pans out “as we con­tin­ue to build a pipeline of small mol­e­cule ther­a­peu­tics for pa­tients with can­cers and oth­er dis­eases.”

Jay Brad­ner No­var­tis

The fo­cus at Nurix, and now Gilead, is the ubiq­ui­tin sys­tem and key en­zymes called E3 lig­as­es. Pro­tein degra­da­tion has proved a promis­ing ap­proach in on­col­o­gy, at­tract­ing a group of play­ers to the field. Arv­inas is one of the most promi­nent, adding an ag deal with Bay­er a few days ago with $115 mil­lion built-in up­front. But it is by no means play­ing so­lo in the sec­ond-gen pro­tein degra­da­tion field. Ri­vals to the pro­tein degra­da­tion ti­tle in­clude C4 Ther­a­peu­tics — out of Jay Brad­ner’s lab at Dana Far­ber be­fore he took the helm at NI­BR — and the start­up Kymera. And not sur­pris­ing­ly, Brad­ner — who now runs NI­BR — re­cent­ly forged a close re­la­tion­ship with UC Berke­ley on pro­tein degra­da­tion as well.

Nurix gets a chance to co-pro­mote drugs in the deal they did with Gilead, pro­vid­ed they pick up half the de­vel­op­ment costs.

So­cial im­age: Er­ic Ris­berg, AP Im­ages

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.