Category: Uncategorized

German Merck Suffers Setback — In Potential MS Candidate, Evobrutinib… So It Goes.

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Thus Sanofi’s Aubagio® (the current standard of care, in MS) remains the top of the heap. Many pharmacos were looking at BTK inhibitors as the next generation — for MS therapy. It is fair to say that the Germans’ misses have chilled the entire space. But that — after all — is what science is about: trial and error; and then a redirecting of efforts based on the shared learnings.

Are Biogen, Novartis and Roche each re-evaluating their MS / BTK development programs? We shall soon see. In the meantime, here’s some of Fierce’s fine reporting on it all:

…It’s been a quick fall from grace for evobrutinib. Only months ago, Merck KGaA was outlining hopes for a major commercialization push for the BTK inhibitor — and now the German pharma has dropped the drug completely.

Merck told Fierce Biotech that the decision was made in response to the failure of evobrutinib to beat Sanofi’s Aubagio in two phase 3 multiple sclerosis (MS) clinical trials in December 2023. With Merck having pinned blockbuster hopes on the drug, the pair of failures sent shockwaves through the BTK inhibitor space at the time….

Up to the phase 3 readouts, the company had maintained sky-high hopes for the drug. As recently as November, Merck had outlined plans to support evobrutinib with a major commercialization push, telling investors that launch preparations would drive up costs starting in the fourth quarter and mulling whether to use a voucher to accelerate the FDA review.

On a call with analysts to discuss the earnings results, Merck CEO Belén Garijo admitted the BTK inhibitor’s failure “was no doubt a disappointment….”

Onward, smiling into the Sunday sunshine — for a brisk ride by the lake….

नमस्ते

Trivial — But Interesting, To Me, At Least… At The Main Site…

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I guess I ought to invite my own… absence, more often. Heh.

Unlike at least the prior three years, this past one has seen my traffic spike as I take more extended, off-grid trips… almost exclusively for… pleasure.

But it truly is of no moment, since I never have — and never will — sell ads, or try to monetize my traffic. It is more a tool for gauging reader interest, in my case.

I gather (from my phone calendar) once in a great while, during one of the red trips — I had a quick lunch or afternoon biz meeting there somewhere in the middle, but mostly… I am out of pocket, and posting far less material during the red arrow intervals, at right.

So… I’d guess the data in 2023… says I am a man who has much about which to be… modest. Hah! Onward.

नमस्ते

Of Hinderaker’s Thinking: Fish Need… Bicycles?!

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Welp. We all well now know that the GOP / MAGAts see the coming light, in the tunnel… and most of them are finally figuring it out — it is an oncoming freighter, under a head of steam. That’s Mr. Biden — post, the SOTU.

So John this morning clutches at straws.

He complains that Mr. Biden’s speech started late, due to a protest on the streets of DC tying up traffic for about 10 minutes.

Okay. Whatever — the First Amendment is still… a thing, John.

But he goes on to equate this 10 minute tie up to… wait for it: January 6 2021.

You know, when ruffians stormed the Capitol, killed people in the process, and tried to find and hang the GOP Veep, all on the “Cheeto-lini’s” exhortations to stop his winning opponent from being certified as the new Commander in Chief.

Yes. Those two things are… fish and bicycles, John.

Your senility is showing, man.

Out.

Power Alley Saturday: We Have Said For Quite A While That Wall Street Has Under-Estimated Keytruda®’s Patent Life [Extenders]…

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Much of the current analysts’ writing — at Wall and Broad — operates from the assumption that when Merck’s first patent on pembrolizumab (branded as Keytruda®) expires, a generic / biosimilar “gold rush” will take place. The bulk of them put that as a 2027 event (and harm Merck’s present, and future cash flow juggernaut).

As I’ve said for over four years, here — that misunderstands the way the patent law in the US favors… extensions, and new formulations. To be sure, at over $25 billion a year in revenue, there will be many competitors hoping to enter, with bio-similar versions… but Merck is presently conducting several Phase 2 and Phase 3 studies showing that a much more convenient “shot version” (subcutaneous) — as opposed to an hours long IV drip version, as presently patented — will do the job just as well.

Candidly, that effort (based on already-well-known, “generally recognized as safe” processes) is nearly certain to deliver, in demonstrating comparable efficacy — i.e., succeed, and thus support an entirely new FDA approval (and new US issued patents, to boot!) — for this far more convenient formulation.

By my lights, this would extend the highest margin markets’ patent protection to the mid-2040s. And there may well be other reformulations, or combos-, that make the old IV patented version… less attractive in the high-end oncology suites.

Sure, the generic manufacturers will come with various bio-similars, but those — relegated to the IV formulation — will be seen mostly in China and Russia, and India… and eventually parts of Sub-Saharan Africa, and South America. But that will be, net-net, only about five to ten percent of the overall revenue — and less than one to two percent of the profits, that Keytruda will be racking up, as a subcutaneous injection… in the EU, UK, Australia and Japan — and of course, the vast US and Canadian markets.

That is my candid assessment. So, in general — this is in no manner akin to the situation in 2008-09 that legacy Schering-Plough faced when one franchise was over 65 percent of the company profits, and over 40 percent of the company revenue… and was then determined to be an expensive placebo. Do trade with this in mind, as you look at Merck around $123 a share on the NYSE.

It has quite a bit of blue sky ahead, in a series of wildly profitable, and vitally life saving markets, around the globe. Smile.

नमस्ते

Bill Otis Wrote A Thing BEFORE The SOTU. I Doubt He Believes It, Now.

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Read it solely for its comical appeal — if you do decide to read it, at all.

But to be fair — he wrote it about 20 hours before Mr. Biden delivered his SOTU.

Yes we are still eight months away from voting.

But Bill is correct that there is a probable scenario where Cheeto-lini is a convicted felon by then. And in this new world, that well may be lethal. And that is after the public will have seen headlines for days that he’s had to post over $600 million in bonds, in the courts, due to his losses on fraud charges — and on libel and defamation. Libel and defamation related to his lies about forcibly sexually assaulting a woman in a dressing room in a Manhattan department store.

So Bill’s headline gets it… exactly bass-ackwards. It is Cheeto who is DOA.

Out.

John Keats’ Headstone Reads “Writ in Water…” — And The Forthcoming JPL Europa Clipper Mission Will Take Him Literally At His Word…

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John Keats1 had once penned a few lines… and then asked that one part in particular, be inscribed on his tombstone — as he lay dying at 25, in 1820. So it reads “here lies one whose name is… writ, in water…” — so true. All of our lives, it seems, are writ in water — ethereal, beautiful, fragile and fleeting.

And the mission to search for water, on Europa, called Clipper — will carry a tile with the wave form of human voices, in over 100 languages… saying the word “water”.

We need not explain why the finding of that silvery liquid on out-worlds means… everything, in our search for life, like ours. Just know that Mr. Keats is… smiling, this evening… somewhere, out there. Here’s the story, for a rain-soaked Friday:

…Made of the metal tantalum and about 7 by 11 inches (18 by 28 centimeters), the plate features graphic elements on both sides. The outward-facing panel features art that highlights Earth’s connection to Europa. Linguists collected recordings of the word “water” spoken in 103 languages, from families of languages around the world. The audio files were converted into waveforms (visual representations of sound waves) and etched into the plate. The waveforms radiate out from a symbol representing the American Sign Language sign for “water.”

To hear audio of the spoken languages and see the sign, go to: go.nasa.gov/MakeWaves.

In the spirit of the Voyager spacecraft’s Golden Record, which carries sounds and images to convey the richness and diversity of life on Earth, the layered message on Europa Clipper aims to spark the imagination and offer a unifying vision….

Ada Limon’s sublime poem appears on the reverse of this tile. Onward, smiling here in the steel and glass canyons… ever, smiling:

नमस्ते

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1. An earlier version of this post had mis-attributed the quote to William Butler Yeats. In was, in fact, John Keats, nearly a century earlier. The mistake was the author’s alone. So it goes.

Just The Tip Of The Iceberg — $93 Million Bond, Signed By Cheeto-lini, In Carroll Libel Judgment Case.

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Well… this ABSOLUTELY has to be a first: the presumptive GOP nominee in ’24 has just posted a $93 million — insurer backed — bond, in the Southern District of New York, and it will shortly be followed by a perhaps nearly $500 million bond, in state court in New York (on the fraud judgment)…

The GOP is backing a guy who owes, under judgments of competent courts — nearly $600 million for fraud — and Libel. Libel involving a forcible sexual assault.

This is the best guy they could find.

But — if it means the Democratic Party retains the West Wing of 1600 Penn, for another four years…. I concur.

Let Tangerine lose… and lose… and… lose.

Onward.

In Friday Ebola Research News… Promising In Vitro Results, From A Strain Of Perhaps The Planet’s Oldest Bacterium…

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To be clear, this would be a therapeutic, not a vaccine. For use in humans who’ve already presented with symptoms of Ebola.

Of the potentially greatest significance, it can be safely stored at room temperature, rather than the deep sub zero temps needed (and in scarce supply, in much of rural Africa) for the current and effective vaccine stocks.

The team at the University of Nebraska is beginning mouse models this year. We will keep our fingers crossed, but here is the story, from Phys.org:

…Nebraska’s Shi-Hua Xiang, Joshua Wiggins and colleagues took a special interest in scytovirin, a type of lectin produced by cyanobacteria, likely the Earth’s first oxygen-producing organisms. Because scytovirin had shown some early success in inhibiting Ebola, the Husker team went about engineering two strains of lactic acid bacteria, which can safely colonize the human body, to display scytovirin on their own surfaces. The study is published in the journal Frontiers in Microbiology.

After constructing research-safe shells of Ebola particles, the virologists introduced them to the two bacterial strains. Their experiments revealed that one of the engineered strains, Lactococcus lactis, could neutralize roughly 54% of the Ebola particles—more than twice the rate of scytovirin-free L. lactis.

Xiang, Wiggins and the team are now testing their bacteria-delivered antiviral in mice, where the virologists are determining whether the engineered L. lactis can neutralize Ebola the way it did in cell cultures. Passing that test could eventually lead to human trials.

If it does continue to perform, L. lactis — which is already used to make cheese and buttermilk — could become a relatively simple, inexpensive, long-term way to protect vulnerable populations against the devastating virus, the team said….

Now you know — a hopeful time, for advances in human disease management sciences. Onward.

नमस्ते