Mer­ck high­lights cru­cial hit for Keytru­da in sec­ond-line esophageal car­ci­no­ma — but there are al­so 2 miss­es

Mer­ck has un­veiled a Phase III da­ta pack­age back­ing Keytru­da’s case as a sec­ond-line treat­ment for the tough in­di­ca­tions of esophageal and esoph­a­gogas­tric junc­tion car­ci­no­ma, un­der­scor­ing its ear­li­er con­fi­dence that the PD-1 in­hibitor rep­re­sents a sig­nif­i­cant ad­vance in this field de­spite on­ly hit­ting one of three pri­ma­ry end­points.

The key num­ber the com­pa­ny wants to fo­cus on is 31% — the de­gree by which Keytru­da re­duced the risk of death com­pared to chemother­a­py in pa­tients with squa­mous cell car­ci­no­ma or ade­no­car­ci­no­ma, who had pro­gressed af­ter stan­dard ther­a­py and whose tu­mors ex­pressed PD-L1 (as quan­ti­fied by a com­bined pos­i­tive score, or CPS, of 10 or above).

That sub­group, which con­sti­tutes 222 out of 628 to­tal pa­tients in the KEYNOTE-181 study, reached a me­di­an OS of 9.3 months ver­sus 6.7 months for the chemo group. They al­so had a 12-month OS rate of 43% while the chemo arm ex­pe­ri­enced 20%.

These are pa­tients whose can­cer — in the esoph­a­gus or the esoph­a­gogas­tric junc­tion — pro­gressed af­ter ini­tial treat­ment, fol­low­ing a poor prog­no­sis to be­gin with, re­searchers added.

For the en­tire in­ten­tion-to-treat pop­u­la­tion, though, the dif­fer­ence in OS be­tween two arms was not sta­tis­ti­cal­ly sig­nif­i­cant with a me­di­an OS of 7.1 months for both treat­ment groups. Same goes for the oth­er sub­group an­a­lyzed for the study — the 401 pa­tients with squa­mous cell car­ci­no­ma — with the Keytru­da group see­ing a me­di­an OS of 8.2 months com­pared to 7.1 months in those re­ceiv­ing chemo.

These fail­ures kept in­ves­ti­ga­tors from for­mal­ly test­ing the sec­ondary end­points, mean­ing that we won’t know the pro­gres­sion-free sur­vival and ob­jec­tive re­sponse rate.

Mean­while, a sep­a­rate Phase III study — dubbed KEYNOTE-590 — is putting the block­buster check­point in­hibitor to first-line use in com­bi­na­tion with chemother­a­py for pa­tients with esophageal car­ci­no­ma.

Ri­vals are lin­ing up their own shots at esophageal and esoph­a­gogas­tric can­cers, with late-stage of­fer­ings from chief ri­val Bris­tol-My­ers Squibb. Cel­gene and BeiGene, which were slat­ed to notch the 7th PD-1 ap­proval in the US, were al­so in the game, though the pro­gram’s fate re­mains un­clear as Bris­tol-My­ers com­pletes its $74 bil­lion ac­qui­si­tion of Cel­gene.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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Genen­tech plots $53M dis­cov­ery quest aimed at spark­ing a 'Holy moly' piv­ot in neu­ro R&D

Genentech has committed $53 million to back a 10-year quest aimed at going back to the drawing board to use new technology and fresh scientific insights to generate a pipeline of drugs for neurological diseases.

Roche’s big South San Francisco hub will mix it up with the scientists drawn together for the Weill Neurohub — formed in 2019 as a joint research partnership involving UCSF, Berkeley and the University of Washington — in an exploration of the field to develop new therapies for some of the toughest diseases in drug R&D: Alzheimer’s, Parkinson’s, Huntington’s, ALS and autism.

Am­gen, As­traZeneca speed to­ward fil­ing next-gen an­ti­body for asth­ma af­ter un­cork­ing full late-stage da­ta

On the hunt for a novel competitor to Sanofi and Regeneron’s Dupixent in severe asthma, Amgen and AstraZeneca posted “exciting” results from their next-gen antibody late last year. Now, the partners are showing their hands, and the results look good enough for approval.

Amgen and AstraZeneca’s tezepelumab plus standard of care cut the rate of severe asthma attacks by 56% at the one-year mark compared with SOC alone, according to full data from the Phase III NAVIGATOR study presented Friday at the virtual American Academy of Allergy, Asthma & Immunology meeting. And those significant results were consistent regardless of patients’ baseline eosinophil counts.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

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Glax­o­SmithK­line re­thinks strat­e­gy for Covid-19 an­ti­body — not the Vir ones — af­ter tri­al flop. Is there hope in high-risk pa­tients?

In the search for a better Covid-19 therapeutic, GlaxoSmithKline and Vir have partnered up on two antibodies they hope have a chance. GSK is also testing its own in-house antibody, and early results may have shut the door on its widespread use.

A combination of GSK’s monoclonal antibody otilimab plus standard of care couldn’t best standard of care alone in preventing death and respiratory failure in hospitalized Covid-19 patients after 28 days, according to data from the Phase IIa OSCAR study unveiled Thursday.