Monday, March 18, 2024

Trump Has Been Unable To Find A Bond Insurer/Issuer, For The $454 Million He Needs, To Appeal His Fraud Loss In NY State At The Hands Of The Able AG's Office...


So his lawyers report, into the court, by letter this morning. It seems obvious, that if one claims to be worth many billions, one should not expect that the court will "waive" a bond, on a figure one owes to the people of the State of New York, to appeal.

Trump was found liable, at trial for $454 million (and over $500 million, when interest is added). That is money he owes to the State of New York. His own IOU -- as a fraudster -- cannot be adequate. So, it is likely he will not appeal -- since there is no "right" for fraudsters to escape paying their judgment debts, on time. From The Hill's reporting, now:

. . .“Defendants’ ongoing diligent efforts have proven that a bond in the judgment’s full amount is ‘a practical impossibility,’” the lawyers wrote, citing an affidavit signed by an insurance broker who testified for Trump during the trial last year.

Trump’s attorneys claim they have spent “countless hours negotiating with one of the largest insurance companies in the world” and have approached 30 companies to back the bond, efforts they said they were pursuing before the judgment was made.

“The amount of the judgment, with interest, exceeds $464 million, and very few bonding companies will consider a bond of anything approaching that magnitude,” Trump’s lawyers wrote. . . .


Cry me a river.

If you hadn't defrauded the hard-working taxpayers of New York, you wouldn't be in these straights. Time to sell Mar-a-Lago? I'd hope so, but he probably cannot close the sale, and raise the cash before next week. He may be. . . done. [And the court may accept an IOU, but I'd say that looks a lot like the rich get better treatment at law, even after being found liable for a half-billion in frauds. The vast scale of his frauds should not be rewarded, now that he cries. . . poor.] Grin.

नमस्ते

Sunday, March 17, 2024

[U: Video Below -- Do Watch It All!] Elon Musk Has (Again) Established That He Only Cares For Free Speech That Flatters... Him.


Admittedly, this is a bit of a tangent. . . but since my Buffs will ultimately face Marquette, if they can get past Florida, in the big dance. . . I am going to be swaying off-topic anyway, this week (picking brackets again, against Mr. Obama -- assuming he fills some out this week).

The good news is. . . they are in. The bad news, is that I now have to pick between Marquette, a legit final four team -- and my heart: the Buffs (in a round of 32 game). Ah. . . first world problems, to be sure.

Speaking of which -- Elon Musk apparently doesn't like answering non-fawning questions -- and doubly so, if it is a smart-mouth man of color as his uncontrolled interlocutor. Do enlarge and read the entire statement at right. And as soon as the interview is posted in full on YouTube, I will place it below.

Musk should have been smarter than this. Once he agreed to sit, he was never going to prevent its very wide airing. And all he's done is give Mr. Lemon and even wider, more committed opening audience. One he can no longer monetize, via his X-itter.

Hilarious. Look in, right here -- for an update with the video tomorrow evening. Onward.



नमस्ते

More Promising Ebola Replication Research -- Montreal, Rutgers And Texas Collab: Using Ubiquitin As Camouflage


A few months ago, we reported on this same Texas team's discovery that Ebola virus (like HIV) can travel over 200 microns, along nanotubes -- to escape antibody defenses, and reprogram new and otherwise healthy human cells to corrupt purposes.

Now, along with Canadian colleagues, and biologists at Rutgers, the team has sussed out that a naturally produced human protein, called ubiquitin, is being used as "camouflage" -- for the virus to stealthily take over cells, while evading the white cell hoards of the body's defense mechanisms.

Here's the latest, from Phys.org:

. . .By shedding light on how the virus interacts with a human protein called ubiquitin, the researchers have also identified a potential target for new drugs to prevent the disease.

Published in PLOS Biology, the study involves pharmacologists at Université de Montréal, infectious-disease specialists at Rutgers University, and microbiologists, immunologists and pathologists at the University of Texas Medical Branch (Galveston). . . .

"Advanced computational modeling by our team here at UdeM predicted the binding interface between a viral protein, VP35, and the ubiquitin chains in human cells, and identified potential chemical compounds that could disrupt this interaction," he said.

"This discovery not only deepens our understanding of how the virus works, but also offers a promising avenue for the creation of more effective therapies. In particular, it paves the way for the design of drugs capable of disrupting this interaction and slowing down viral replication. . . ."


Now you know. Onward, with a crinkly eyed Irish smile. . . be excellent to all you meet, today and always.

नमस्ते

The Icelandic Eruptions On Reykjanes Peninsula -- Renewed. And Wear Green...


We've been tracking this for about six months, and it seems like the Earth is shuddering on St. Patrick's, so we will mention it again on a quiet Sunday morning here.

Here's the latest -- on the new eruption, via The UK Guardian:

. . .Emergency teams worked through the night to bolster defensive barriers around the evacuated fishing town of Grindavik as lava from the fourth volcanic eruption on Iceland’s Reykjanes peninsula since December flowed towards it.

After weeks of warnings that semi-molten rock was building up under the ground, the Icelandic Meteorological Office (IMO) said the eruption, at 8.23pm local time (2023 GMT) on Saturday, had opened a nearly 3km-long fissure in the earth between two mountains.

Lava was flowing mainly south and south-east at a rate of about 1km an hour overnight and could reach the ocean, the IMO said. Defensive dykes and barriers were being reinforced to stop the “significantly wider” lava bed wrecking the main coastal road. . . .


Wild Earth sciences. In addition, another one of those shiny silver 12 foot tall monoliths was spotted last week, in Wales, atop a knoll called Hay Bluff. But it is pretty clearly a clever knock off, so we won't cover it (ref. 2020 and 2021 coverage). Onward!

In addition, the Buffs are waiting to hear if they've made the NCAAs -- or if they are relegated to the NIT, after a tough loss to Oregon in the last ever PAC-12 championship game. Sending some mo jo to. . . Boulder, now! And that's all the trivia I've got for the morning -- with a newly-replaced 2021 masthead, from their last March Madness NCAA berth. Grin.







नमस्ते

Saturday, March 16, 2024

Musk Did Reach Orbit, But His "Re-Entry" Stage Suffered An Anomaly, As The Main Capsule Reached Orbit.


Still, nice progress. The goal though, is perhaps over a decade off, now. See, the goal is boots on Mars. And for that, this failed stage / booster would need to remain in stable orbit, for an eventual crewed re-entry. Without it, the crew cannot get home.

So yes -- this is still several iterations away from any crew headed toward the Red Planet. Here's the rest, from NASA:

. . .As part of NASA’s Artemis campaign to return humans to the Moon for the benefit of all, the agency is working with SpaceX to develop the company’s Starship human landing system (HLS), which will land astronauts near the Moon’s South Pole during the Artemis III and Artemis IV missions. On March 14, SpaceX launched the third integrated flight test of its Super Heavy booster and Starship upper stage, an important milestone toward providing NASA with a Starship HLS for its Artemis missions.

A complement of 33 Raptor engines, fueled by super-cooled liquid methane and liquid oxygen, powered the Super Heavy booster with Starship stacked on top, from the company’s Starbase orbital launch pad at 8:25 a.m. CDT. Starship, using six Raptor engines, separated from the Super Heavy booster employing a hot-staging technique to fire the engines before separation at approximately three minutes into the flight, in accordance with the flight plan. This was the third flight test of the integrated Super Heavy-Starship system. . . .

“Storing and transferring cryogenic propellant in orbit has never been attempted on this scale before,” said Jeremy Kenny, project manager, NASA’s Cryogenic Fluid Management Portfolio at Marshall. “But this is a game-changing technology that must be developed and matured for science and exploration missions at the Moon, Mars, and those that will venture even deeper into our solar system.”

Under NASA’s Artemis campaign, the agency will land the first woman, first person of color, and its first international partner astronaut on the lunar surface and prepare for human expeditions to Mars. . . .


Onward -- life is a. . . journey -- not a destination. Onward to St. Patrick's, on this weekend's journey. . . . smile.

नमस्ते

Friday, March 15, 2024

Final Validation Of Merck's Keytruda In Front Lines -- Advanced Cervical Cancers, In Conjunction With Chemo...


We had mentioned that the interim readout allowed for an approval in first line cervical cancers, last year.

The definitive data is in, and it validates the FDA's early approval of this indication.

Good news for Rahway. . . to be sure, but completely. . . expected.

And as a bit of a tangent. . . worldwide, according to the WHO, cervical cancer is still the most common form of cancer that women face.

Many cogent oncologists, and infectious disease experts, argue there is strong evidence that cervical cancers stem (in part) from exposure to HPV (an STD). And Merck sells a very effective vaccine for HPV, but it obviously must be dosed before any exposure. Thus the argument for pre-teen vaccination. . . and the related push-back, from some parents who don't want to be seen as encouraging sexual experimentation, by their pre-teens. [My own view is that it is better to. . . accept the reality of these modern situations, as a parent, than to wish about a mythical world -- one that never really existed.]

So to return to the main point, this finding is. . . immaterial. Already priced in.

Onward, grinning to a fun lunch in the steel and glass canyons. . . be excellent to one another.

नमस्ते

Thursday, March 14, 2024

Merck Has Asked For An "Inter Partes" Review, At The US Patent Office, Of Johns Hopkins' Patents -- Ones Hopkins Claims Read On... Keytruda.


As we have said for several years now, Rahway is not likely to lose patent protection much before 2040, on this ultra blockbuster franchise -- and this step, as ably reported by Fierce Pharma, is designed to cement that outcome.

JHU sought four patents, all of which were granted by the USPTO examiner -- and all of which, Merck correctly asserts were based on joint research with Merck -- and funded entirely by Merck. The patents go to ways of making the agent more effective in a human body (dosing, etc.) which were in fact Merck's prior art / know-how (unpatentable) from the clinical trials Merck funded and conducted. At best, JHU might argue it deserves a "tip" for filing on them, but it is unlikely that the JHU '356 '974,'975 and '219 patents will ultimately be held to require that Rahway must pay licenses, for them (if ultimately allowed to stand). It was primarily Merck's effort that led to these method of use patent claims at JHU.

In any event back in 2022, in federal court in Maryland, Merck began litigation to invalidate these JHU patent claims. Here's the latest, from Fierce:

. . .Merck is kicking its Keytruda-related clash with Johns Hopkins University (JHU) up a notch by asking the U.S. Patent and Trademark Office (PTO) to weigh in following a 2022 complaint.

The drugmaker last week filed petitions for inter partes review proceedings on four Keytruda-related patents owned by JHU, JD Supra reported March 13.

Inter partes reviews essentially seek a determination on the validity of a patent. In Merck’s case, its petitions propose the patents as being obvious and anticipated by the prior art. . . .

[Ed. nota bene -- In Merck's complaint, it stated "JHU faced repeated rejections (from the PTO) for the use of “wherein” in certain claims requiring an improved outcome comparison. In attempting to overcome the Patent Office’s rejections, JHU referred to the claim limitation, “wherein the patient exhibits an outcome that is improved as compared to a corresponding outcome that would be observed in a reference patient that has been administered pembrolizumab,” and represented that, “this clause” was necessary to prevent the claim from “simply requir[ing] giving an effective amount of pembrolizumab to a patient,” which would “effectively ignor[e] the unexpected relationship between MSI-high/MMR deficiency status and anti-PD-1 antibodies, as described in the specification.”

JHU argued that, to omit this clause from the presented claims, would “ignore a core concept disclosed in the specification: the unexpected relationship between MSI-high/MMR deficiency status and improved relative response to anti-PD-1 antibodies. . . .” But in Condor's estimation, these are not novel claims as made by JHU.]


Now you know -- but at over $22 billion a year in cash revenue now, Merck is going to move forcefully to keep all interlopers off its playing field (even university affiliated ones) -- by litigation, inter partes challenges and "evergreening" formula and delivery changes (like subcutaneous injection versions of the therapy). . . into the 2040s time frame.

You read it here first. Onward, smiling -- happy Pi Day '24!

नमस्ते

Wednesday, March 13, 2024

"Space Is Hard" (Again!) -- A 59 Foot Privately-Funded Uncrewed Japanese Launch Vehicle (Solid Fueled)... Explodes On Liftoff, Today.


I must say it is admirable, that private industry continues to try, and try, to reach orbit. Especially our international friends.

But make no mistake. . . they call it. . . "rocket science" -- for a reason. It is. . . daunting. Here's the latest from NBC, after another Japanese private contractor "hard landed" on the moon eleven months ago, in another robotic mission disappointment.

. . .Space One’s small, solid-fueled Kairos rocket exploded shortly after its inaugural launch on Wednesday as the firm tried to become the first Japanese company to put a satellite in orbit.

The 59-foot, four-stage solid-fuel rocket exploded seconds after lifting off just after 11:01 a.m. (10:01 p.m. Tuesday ET), leaving behind a large loud of smoke, a fire, fragments of the rocket and firefighting water sprays near the launchpad, visible on local media livestreams of the launch on the tip of mountainous Kii peninsula in western Japan.

Space One said the flight was “interrupted” after the launch and that it was investigating the situation. There was no immediate indication of what caused the explosion. . . .

Tokyo-based Space One was established in 2018 by a consortium of Japanese companies: Canon Electronics, the aerospace engineering unit of IHI, construction firm Shimizu and the state-backed Development Bank of Japan. Two of Japan’s biggest banks, Mitsubishi UFJ and Mizuho, also own minority stakes. . . .


Now you know -- and our sincere condolences go out to Space1's whole team. But pick yourself up, and dust yourself off -- and try. . . again. Onward.

नमस्ते

Thesis: AI (At Least In Its Current Iteration) For Financial Analysis... Is Largely... Useless -- Merck Edition.


But I did find the goofy / freebie graphic (see derivative version at lower right), in an otherwise useless piece of fluff. . . at least interesting, as a way to think of Merck's vast financial prowess. [The company generates a 73% gross margin, or over $10 billion cash, each year now. And the flow is a quarterly set of figures.]

The AI generated content / editor was arguing that the flow meant Merck's dividend was at risk. That's preposterous, as we've said a few times before. But what it does highlight, is mostly the opposite case: Merck's vast cash flows are largely (and appropriately) managed, globally to minimize tax exposures.

And even so, it generated $10.7 billion in gross income before taxes last year. Were it willing to pay hefty repatriation taxes, a far larger number would flow to the bottom line, and be "brought home" as EPS each year. But it makes more sense to keep investing that money in Europe and the UK and Asia. . . to grow its overall businesses' profits in lower-tax jurisdictions.

So, what the AI chart actually shows. . . is only that, if Merck didn't mind paying more in income taxes in the US, it could instantly increase (not cut!) the dividend. But its yield is still pretty nice and fat, even with the stock sitting above $120/share on the NYSE most mornings, now. So. . . all in all, a "complete do over" for that AI engine. Cheers.

नमस्ते

Trivia Break -- We Always Enjoy a Great Slice... But We'll Wait Until 1:59 pm, Tomorrow -- While Many Others Awaken At 1:59 am, To Celebrate...


I do love math -- yep, I'm a math nerd.

I devour off-kilter coincidences -- sometimes found in numbers. So, a small confession: quite a long while ago, while at the hospital awaiting the birth of our middle son (things were stalled at that point, so -- while watching Jordan get 45 in the Garden, and the purple M&M introduction turn the Empire State Building that shade). . . on a scrap of paper, I started sorting the digits of Pi into a pyramid. And it turns out that. . . if you break the top nine lines of the "pyramid" at the right spots, the edges are all identical. For at least the first 11 or so lines; and it forms a near perfect triangle, depending on the font.

Then, plainly overjoyed with my second's arrival, I promptly forgot about that scrap of paper, from the delivery room.

And. . . several decades later, one of my brothers picked up on the thought -- which I mentioned in a passing phone conversation. As he had lots of time on his hands, the mug at right resulted. Okay, now you know.

I won't rise at nearly 2 am -- I will wait until mid afternoon tomorrow -- but trust that I will partake of a slice of tart cherry pie, when I do. I'll wash it down with hot coffee and cream.

And think of the three dimensional pyramids, somewhere still lost to the sands of time -- and wonder whether the Egyptians or the Kushites. . . carved these same repeating-edge digits into the stone blocks on the corners (in some language we can no longer read).

Whoosh. Enjoy, one and all, come tomorrow -- whenever you celebrate that most useful of numbers!

नमस्ते

Tuesday, March 12, 2024

Tangent Alert: Huge "Energy-Waster" Of A Company... Invests Some Seed Money In "Waste To Energy" Company?! Hilarious!


From time to time over the prior eight or so years, we've discussed this silly Bitcoin "miner" -- which is '34 Act registered (for now) on the NASDAQ. It has never made a penny of GAAP EPS, from continuing operations, life to date -- nearly eight years, now. But it has paid executives over $200 million in compensation -- to lose perhaps $1.2 billion in that time. Insane, in a word.

So. . . today, Riot Platforms announced that it has dumped some of the cash it doesn't earn, from EPS it doesn't produce -- as a vast "energy wasting" company. . . into a company that is actually trying to generate meaningful levels of "reclaimed" energy -- from post consumer waste, in landfills -- by capturing synthesized methane, down in dusty West Texas.

Got all that?

Good. All this money came directly from rube-shareholders, throwing good money after bad.

And even with Bitcoin above $73,000 (and a new all time high) for part of the day, today -- Riot keeps falling, on the NASDAQ.

Hilarious. Here (below) are the specifics (insofar as they've been disclosed), but since no dollar amount was disclosed, the actual cash outlay is likely under $15 million, since that would end up below the materiality threshold -- which must be disclosed under SEC rules. But I suppose it is equally likely that it is a material amount, and Riot intends to bury it, in some R&D line, rather than as an equity method "investment".

We shall see, as the two guys behind Reformed Energy are themselves former -- and failed -- small scale Bitcoin miners:

. . .Reformed Energy Inc., a Texas corporation, announced today that it has secured a strategic investment from Riot Platforms, Inc. ("Riot"), marking a significant milestone for the company as it seeks to bring its unique plasma gasification technology to full commercialization.

By processing solid and liquid waste streams in its closed plasma gasification system, Reformed Energy can effectively prevent over 99% of the methane emissions and pollution that occurs with traditional waste disposal methods while reducing the physical volume of waste by about 90%. This process yields a versatile synthesis gas that can be utilized downstream for sustainable power generation and synthetic fuel production. In short, the company's unique technology has the ability to clean up existing landfills and reduce incoming waste streams.
The self-contained system does not require grid interconnection and generates carbon neutral power while actively reducing existing methane emissions
. . . .


And yet. . . Riot remains below $11.60/share on the NASDAQ. Precious -- with BTC over $72,000 -- a pure bubble figure.

O U C H.

नमस्ते

Pearl Bio Snags A Bio-Bucks Validation Deal With Merck -- Could Reach $1 Billion, On Milestones -- For "Smart" Biomaterial "Jewels".


Rahway continues to wisely invest / use its dividends / payoffs from the cash cow Keytruda, to take multiple, diverse "shots on goal" -- for the next big thing in oncology, and bio-science, more broadly.

Today's news brings a collab with Pearl Bio, which is a spinoff of the work of the legendary George Church (think re-animating wooly mammoths, here!), and some very well-respected Yale biologists (pictured). It is being run through a Series A round by former lawyer Amy Cayne-Schwartz -- also with a Yale affiliated pedigree, and has raised quite a bit already. As it is private, of course, exact terms have not been disclosed, but many power players in bio- space are piling in.

Here's the latest, on the story from Fierce Biotech, but this whole relationship is clearly not (yet) material to massive Merck:

. . .Merck has signed up to Pearl Bio’s synthetic biology platform, offering up to $1 billion in biobucks for potentially cancer-busting biologics.

The collaboration could pile more biologics onto Merck’s pipeline and serves as validation for Pearl, which emerged from stealth in June 2023 with the backing of Khosla Ventures. Merck is paying an undisclosed upfront fee and offering up to $1 billion in milestone payments for Pearl to identify biologics to treat cancer.

The biotech describes itself as creating “template-directed biomaterials with tunable properties.” Co-founder, Chief Operating Officer and Chief Business Officer Amy Cayne Schwartz elaborated in an email to Fierce Biotech, describing how the platform can “encode synthetic chemistries to tune therapeutic properties (e.g., half-life, drug antibody ratio).” The company is in the process of raising its series A round, she told Fierce. . . .


Onward, into the warming sunshine here, then. . . smiling. As we've said before -- we applaud Church's creativity, but we aren't sure the world is quite ready for (nor in need of) the "de-extinction" of wooly mammoths, genetically crossed with modern Asian elephants' DNA.

In any event -- ever smiling.

नमस्ते

On An About 2.5 Million Year Cycle, Mars Applies A "Warbler" -- To Earth's Orbit, Via Gravitational "Resonance". And It Affects Our Deep Ocean Currents.


'Tis in many many ways, almost unimaginably. . . sublimely poetic: the small hot red coal -- moaning a gravitational song in the night, 140 million miles off. . . so very far away, and so faint. . . but when given enough time. . . into millions of years. . . that song is enough to stir our own deepest oceans of. . . life. Into whirlpools they tumble, over and over -- across billions of years of time. Over the rocks from the basement of time, itself. Whoosh -- that is amazing, to me.

And, of course, our own emissions are certainly a more profound, and immediate intervening variable -- but it seems on about a 2.5 million year cycle, the orbit of Mars tends to give Earth a nudge -- either elongating or rounding our orbital path around the Sun enough. . . to cause deep, deep whirlpools at the bottom of our oceans.

That in turn drives weather changes at the surface. Climate change, in short. The connection is born out in the sedimentary layers at the bottom of our oceans -- of over 2 billion years. So. . . might there be a way to use this learning, to manage our own deep whirlpool creation mechanism, and help reverse the potential for collapse of the Atlantic Meridional Overturning Circulation? Perhaps -- as it seems our own efforts at reducing emissions are falling woefully short.

Here's that Earth / Planetary science story, from CNN on a Tuesday (and a teaser) -- do go read it all:

. . .For the Earth, this interaction with Mars translates to periods of increased solar energy — meaning a warmer climate — and these warmer cycles correlate with more vigorous ocean currents, the report found.

While these 2.5 million-year cycles affect warming and ocean currents on Earth, they are natural climate cycles and not linked to the rapid heating the world is experiencing today as humans continue to burn planet-heating fossil fuels, said Dietmar Müller, professor of geophysics at the University of Sydney and a study co-author.

The authors describe these currents, or eddies, as “giant whirlpools” that can reach the bottom of the deep ocean, eroding the seafloor and causing large accumulations of sediments, like snowdrifts. . . .


Again -- the age of darkness (ignorance) seems to be receding almost everywhere, except in US (and Russian) politics. For our part, we remain optimistic that rational, principled common sense will prevail, come November -- again. Grin.



नमस्ते

Monday, March 11, 2024

Power Alley: Merck Closes M&A Deal; Now Owns Harpoon Therapeutics, For ~$650 Million...


The Hart Scott Rodino waiting period had expired about a week ago (without an added request from the Antitrust Division), and we mentioned the original inking of the purchase contract, here two months ago. . . but it is now put to bed. The assets are owned by Rahway, as of this morning, and the Harpoon stock symbol has stopped trading -- on the NASDAQ.

Good news -- but even so, as a cogent commenter pointed out in January, there have been some reports of off-target effects in the T-cell engager space (but the patients often face dire circumstances, with SCLC -- without therapy).

Here's the latest:

. . .[Rahway today completed] the acquisition of Harpoon Therapeutics, Inc. (Nasdaq: HARP). Harpoon is now a wholly-owned subsidiary of Merck, and Harpoon’s common stock will no longer be publicly traded or listed on the Nasdaq Stock Market.

“We continue to augment and diversify our oncology pipeline with innovative approaches to help people with cancer worldwide,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “We are pleased to welcome our Harpoon colleagues to Merck and look forward to working together to advance a novel portfolio of T-cell engagers, including MK-6070.”

Harpoon’s lead candidate, MK-6070 (formerly known as HPN328), is a T-cell engager targeting delta-like ligand 3 (DLL3), an inhibitory canonical Notch ligand that is expressed at high levels in small cell lung cancer (SCLC) and neuroendocrine tumors. The safety, tolerability and pharmacokinetics of MK-6070 is currently being evaluated as monotherapy in a Phase 1/2 clinical trial (NCT04471727) in certain patients with advanced cancers associated with expression of DLL3. The study is also evaluating MK-6070 in combination with atezolizumab in certain patients with SCLC. In March 2022, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to MK-6070 for the treatment of SCLC. . . .


[With our second (smaller) graphic, at left, we remind readers of an AI-powered diagnostics deal Merck has, in the oncology space.]

Now you know -- onward, grinning -- sunny here!

नमस्ते

"Aren't You Late... For... JAIL, Mr. Trump?"


Apparently, Tangerine took to his dying social media site tonight -- to decry awards being given to [what he views as] politically correct causes. . . and actors.

But late in the broadcast, he renewed his feud with Jimmy Kimmel. So Kimmel decided to have fun with it, in near real time. He read Trump's blurb, word for word, on air. . . and then asked, incredulously. . .

"Gee. . . it is getting kinda' late out East. . . Mr. President, aren't you just a little late. . . for JAIL?!"

The crowd went. . . wild -- laughing in raucous fashion.

So. . . [except for about 5% of America] all Cheeto-lini achieved tonight. . . was to forcefully remind the rest of us that he is a petty, vain, thin-skinned bitter old man, and that he is indeed eventually headed to. . . prison.

Well done dotard. . . well done.

नमस्ते

Sunday, March 10, 2024

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


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 mean time, 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

Scar Jo -- Flawless, As Katie Britt [Catch The "Get Out!" Reference]


Nothing more need be said -- so, here is her comedic genius (scroll to about the mid-point of the cold open):



For the perhaps 5% of all Americans who found Katie Britt compelling, this past week. . . wake up. Please. . . wake up.

नमस्ते

Saturday, March 9, 2024

Trivial -- But Interesting, To Me, At Least...


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

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

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

Friday, March 8, 2024

John Keats' Headstone Reads "Writ in Water..." -- And The Forthcoming JPL Europa Clipper Mission Will Take Him Literally At His Word...


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 so, 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.