Baltic
Dry Index. 1398 -05
Brent Crude 63.59
Spot Gold 3312 US 2 Year Yield 3.65 -0.02
US Federal Debt. 36.788 trillion!!!
Creditors have better memories than debtors.
Benjamin Franklin
Goodbye Trump tariff whiplash April, as U-turn President Trump’s unpredictability hammered stocks and commodities alike.
Say hello to May’s introduction to Trump’s start of Great Depression 2.0. As with the 1930s, by the end of the current decade, the US and global economies will be very different from Pax Americana 1945-2020.
From May onwards, beggar thy neighbour is the new reality.
Europe stocks set for mixed open ahead of
more earnings, euro zone growth data
Updated Wed, Apr 30 2025 1:02 AM EDT
European stock markets were headed for a
muted open Wednesday, as investors brace themselves for another slew of
earnings along with euro zone economic growth data.
The Stoxx 600 index notched a
sixth straight positive session on Tuesday, extending its longest winning
streak since January. The U.K.’s FTSE 100 meanwhile closed
higher for a 12th session, marking its best run since 2017.
Corporate results will be back in focus,
with Airbus, Mercedes, TotalEnergies, Stellantis, Barclays, GSK, Volkswagen and Societe Generale among
those reporting.
U.S. tariffs have unsurprisingly emerged
as a key theme in early reports, with many companies citing the
difficulty of forecasting, while bank profits beat estimates. Swiss
lender UBS continued
the trend on Wednesday, reporting better-than-expected
net profit of $1.692 billion in the first quarter.
A preliminary reading on euro zone
first-quarter economic performance is due at 10 a.m. in London. Economists
polled by Reuters expect 0.2% growth in the period, following stagnation at
the end of 2024.
Globally, attention remains on U.S. trade.
U.S. President Donald Trump on
Tuesday signed
an executive order softening some of his automotive tariffs,
maintaining a 25% vehicle import rate but reducing the overall level as a
result of additional duties on products such as steel and aluminum.
Asia-Pacific
markets were mixed on Tuesday, as were U.S.
stock futures.
Europe
stocks open to close: earnings, euro zone GDP, U.S. trade talks
S&P 500 futures slip after index posts longest
win streak since November: Live updates
Updated Wed, Apr 30 2025 10:11 PM EDT
Stock futures tied to the S&P 500 were
lower Tuesday evening as traders prepared for a blast of economic data to wrap
up a tumultuous month of trading.
S&P 500 futures slipped
0.4%, while Nasdaq 100
futures lost 0.6%. Dow
Jones Industrial Average futures added 71 points, or 0.2%.
The major averages ended Tuesday higher
after Commerce Secretary Howard Lutnick told
CNBC that the White House was close to announcing a trade deal, but
didn’t name the country. Later in the afternoon, President Donald Trump said
that tariff
negotiations with India are “coming along great” and that the U.S.
could soon strike an agreement with the nation.
In the previous session, the 30-stock Dow
climbed 300 points, while the S&P
500 gained 0.58%. It was the sixth straight winning day for both
indexes, the longest since July for the Dow and since November for the S&P
500. The tech-heavy Nasdaq
Composite gained 0.55%.
April has been a rocky month for markets.
Trump’s sweeping “reciprocal” tariff announcement on April 2 set off a bout of
volatile trading, but the major averages have been gradually narrowing the
month’s losses. Consider that the S&P 500 briefly
entered a bear market on April 7 but has since made a comeback, and is
down just 0.9% this month. The Dow is on pace for a 3.5% loss in April, while
the Nasdaq is about 0.9% higher.
“U.S. equities have picked up the pace as
April 30 rapidly approaches, aiming for the monthly flatline and recouping
losses following President Donald Trump’s tariff barrage,” said Jeff
Buchbinder, LPL Financial chief equity strategist.
Treasury Secretary Scott Bessent noted
on Tuesday that “individual investors have held tight, while
institutional investors have panicked” in the recent market turmoil. These
mom-and-pop investors have been buyers of this
month’s sell-off.
A batch of high-stakes economic reports
that could shed light on how
close the economy is to a recession and dictate the markets’ next move
awaits on Wednesday.
The first reading of the first quarter’s
gross domestic product is expected to show an annualized growth rate of 0.4%,
adjusted for seasonality and inflation, per Dow Jones estimates. Several banks
on Wall Street are already trimming back their GDP estimates, anticipating
negative growth.
The personal consumption expenditures
price index for March is also due in the morning. Economists polled by Dow
Jones see no gain for March and a reading of 2.2% for headline inflation. The
PCE is closely watched by the Federal Reserve and is one of its preferred
inflation metrics.
Investors will also be watching for key
earnings reports from Meta
Platforms and Microsoft,
due in the afternoon.
Stock
market today: Live updates
‘Nowhere to turn': Small businesses dependent on
imports from China are feeling more desperate
Updated 3:08 PM GMT+1, April 29, 2025
NEW YORK (AP) — Major orders canceled.
Containers of products left stranded overseas. No roadmap for what comes next.
The Trump administration raised
tariffs on goods from China to 145% in early April. Since then, small
business owners who depend on imports from China to survive have become
increasingly desperate as they eye dwindling inventory and skyrocketing
invoices.
President Donald Trump seemed
to back down somewhat last week when he said he expected the tariffs
to come down “substantially.” That helped set off a rally in the stock market.
But for small businesses that operate on razor-thin margins, the back and forth
is causing massive upheaval. Some say they could be just months from going out
of business altogether.
The Massachusetts family-owned game
company
Game makers are particularly susceptible
to the tariffs since the
majority of games and toys sold in the U.S. are made in China,
according to The Toy Association.
WS Game Co., based in
Manchester-by-the-Sea, Massachusetts, is a family-owned business that licenses
Hasbro board games like Monopoly, Candy Land and Scrabble and creates deluxe
versions of them. Its most popular line of games come in boxes that look like
vintage books and sell for $40.
The company’s games were featured in
Oprah’s Favorite Things list in 2024 and sold in 14,000 stores in North
America, from big national chains to mom-and-pop stores, said owner Jonathan
Silva, whose father founded the company in 2000.
All of WS Game’s production is done in
China. The tariffs have brought the past 25 years of healthy growth to a
screeching halt.
Over the past three weeks, WS Game has had
three containers of finished games, worth $500,000, stranded in China. It lost
orders from three of the largest U.S. retailers totaling $16 million in
business. And there’s not much Silva can do about it.
“As a small business, we don’t have the
runway or the capabilities to move manufacturing on a whim,” said Silva, who
has 22 employees. He said the tariffs have “disrupted our business and put us
on the verge of insolvency” and estimates he has about a four-month runway to
stay afloat if nothing changes.
“We’re really hoping that cooler heads
prevail,” he said.
Artificial flowers in Kentucky
Jeremy Rice co-owns House, a home-décor
shop in Lexington, Kentucky, that specializes in artificial flower arrangements
for the home. About 90% of the flowers his business uses are made in China.
Rice uses dozens of vendors. The largest
are absorbing some of the cost of the tariffs and passing on the rest. One
vendor is raising prices by 20% and another 25%. But Rice is expecting smaller
vendors to increase prices by much higher percentages.
House offers mid-range artificial flowers.
A large hydrangea head will retail for $10 to $16, for example. China is the
only place that manufacturers higher quality silk flowers. It would take a
vendor years to open a factory in a different country or move production
somewhere else, Rice said.
Rice ordered his holiday décor early this
year. But even after stocking up ahead of the tariffs, he only has enough
everyday floral inventory in to last two to three months.
“After that, I don’t know what we’re going
to do,” he said.
Rice is concerned that the trade war will
wipe out a bunch of mom-and-pop stores, similar to what happened in the Great
Recession and the pandemic.
“There’s nowhere to turn, there’s nothing
to do,” he said.
Tea in Michigan
A tea shop in a Michigan college town is
also caught in the middle of the ongoing tariff fight.
“It’s basically just put a big pit in my
stomach,” said Lisa McDonald, owner of TeaHaus, located in Ann Arbor, home to
the University of Michigan. McDonald has owned TeaHaus for nearly 18 years and
sells tea to customers across the U.S.
Americans drank about 86 billion servings
of tea in 2024, according to the Tea Association of the U.S.A.. Almost all of
that is imported since tea isn’t grown in the U.S. at scale, due to factors
ranging from climate to cost.
McDonald imports loose-leaf tea from
China, India, Kenya, Sri Lanka and other countries. She says her customer base
is “from all over the U.S. and the world.” But she worries there is a limit to
what they’ll spend.
More
China
tariffs squeeze small businesses | AP News
US Consumer Confidence Keeps Falling on
Trump’s Trade War
April 29, 2025 at 11:12 PM GMT+1
As President Donald Trump notches the
first 100 days of his second presidency, the general assessment on Tuesday of
the 78-year-old Republican’s performance for consumers, companies, the economy
and workers was less than celebratory.
US consumer confidence fell
to an almost five-year low in April on growing pessimism about
prospects for the economy and labor market under Trump. According to Conference
Board data released Tuesday, consumer expectations for the next six months
plunged to the lowest level since 2011, thanks in large part to the
administration’s wide-ranging trade war. The share of consumers that expected
business conditions to be worse six months from now rose to the highest level
since March 2009, during the Great Recession.
Corporations meanwhile are battening down
the hatches in preparation for rough seas. General
Motors and JetBlue this
week joined a growing list of companies pulling earnings projections as they
grapple with Trump’s new taxes on their imports. (Trump
beat a fresh retreat on Tuesday, this time in favor of automakers.)
UPS, which also backed
away from its 2025 financial guidance due to what it
diplomatically called “macroeconomic uncertainty,” is planning to be
less circumspect with its employees: It plans to fire 20,000 of them—or
about 4% of its workforce—while shuttering dozens of facilities. It’s a move
reflected more broadly in the American labor market, given that new data
shows job
openings fell last month to the lowest since September.
Nevertheless, the bounce in equities continued Tuesday as investors appeared to set aside the sobering data in favor of bets on Federal Reserve rate cuts and corporate resilience.
US
Consumer Confidence Keeps Falling on Trump’s Trade War - Bloomberg
China’s factory activity drops to a near two-year
low in April as trade tariffs bite
Published Tue, Apr 29 2025 9:39 PM EDT
China’s manufacturing activity fell
more than expected to a near two-year low, sliding into contractionary
territory in April as the escalating trade war with the U.S. hurts
bilateral trade.
The official purchasing managers’ index
came in at 49.0 in April, according to data from the National Bureau of
Statistics on Wednesday, falling below the 50-level threshold, which determines
expansion from contraction, for the first time since January.
That reading missed analysts’ expectations
for a 49.8 contraction in a Reuters poll and marked the weakest level since May
2023, according to LSEG data. The slowdown came after China’s
manufacturing activity grew at its fastest
rate in a year in March, as exporters front-loaded outbound shipments to
avoid higher duties.
The sub-indexes for production and new
orders fell sharply to 49.8 and 49.2, respectively, indicating softer demand in
the manufacturing sector, the official figures show. The gauges on raw material
costs and output prices in the industry also continued to decline, dropping to
47.0 and 44.8, respectively.
In a similar vein, Caixin/S&P Global
manufacturing PMI slowed to 50.4 in April from 51.2 in the previous month,
indicating a modest expansion. Analysts had pegged the private-sector survey
index at 49.8.
The official PMI for non-manufacturing
activity, which encompasses services and construction, declined modestly
to 50.4 in April from 50.8 in the previous month.
The bureau’s senior statistician Zhao
Qinghe attributed the slowing factory activity to “drastic changes in the
external environment” in a Chinese statement, translated by CNBC. Zhao added that
China will “coordinate domestic economic work and international trade disputes”
going forward, with a focus on bolstering employment, supporting businesses and
stabilizing the markets.
Zhao also reiterated Beijing’s stance that
“no one stands to win in a tariff war,” citing the U.S. manufacturing PMI
at 49.0 in March.
More
China's
factory activity drops to a near two-year low in April as trade tariffs bite
In other news, Great Depression 2.0 starts in
May.
Carney wins Canadian election, while Conservative
leader loses his seat in Parliament
Updated 12:27 PM GMT+1, April 29, 2025
TORONTO (AP) — Canadian Prime Minister
Mark Carney’s Liberal Party has won the federal election, capping a stunning
turnaround in fortunes fueled by U.S. President Donald Trump’s annexation
threats and trade war.
Carney’s rival, populist Conservative
Party leader Pierre
Poilievre, was voted out of his seat in Parliament, the Canadian
Broadcasting Corporation projected Tuesday.
The loss of his seat representing his
Ottawa district in Monday’s election capped a swift decline in fortunes for the
firebrand Poilievre, who a few months ago appeared to be a shoo-in to become
Canada’s next prime minister and shepherd the Conservatives back into power for
the first time in a decade.
But then Trump
launched a trade war with Canada and suggested the country should
become the 51st state, outraging voters and upending the election.
Poilievre, a career
politician, campaigned with Trump-like bravado, taking a page from the
“America First” president by adopting the slogan “Canada First.” But his
similarities to Trump may have ultimately cost him and his party.
The Liberals were projected to win more of
Parliament’s 343 seats than the Conservatives. It wasn’t immediately clear if
they would win an outright majority — at least 172 — or would need to rely on a
smaller party to pass legislation and remain in power.
Elections Canada said it has decided to
pause counting of special ballots — cast by voters who are away from their
districts during the election — until later Tuesday morning. The Liberals were
leading or elected in 168 seats when the counting was paused, four short of a
majority. Elections Canada estimated that the uncounted votes could affect the
result in about a dozen districts.
The decision means Canadians won’t know
until later in the day whether Carney’s Liberals have won a minority or
majority mandate.
More
Carney
wins Canadian election, while Conservative leader loses his seat in Parliament
| AP News
‘It’s unlike anything we have seen before’: European Union left reeling after Trump’s first 100 days
Published Tue, Apr 29 2025 12:59 AM EDT
European leaders have been left reeling
after the first 100 days of U.S. President Donald Trump’s second term saw
increasing geopolitical and trade turmoil.
“It’s unlike anything else we’ve seen
before from the U.S. administration,” European Union foreign policy chief Kaja
Kallas told CNBC’s “Europe Early Edition” when asked what Trump’s first 100
days have meant for the bloc so far.
Kallas told CNBC’s Silvia Amaro it had
been a “very intense” and “disruptive” time, adding that there was “a lot of
unpredictability.”
“So this is how we have been operating to
try to manage with the new administration,” she said.
Europe faces mounting uncertainty on two
fronts as a result of Trump’s policies: trade and Russia’s war on Ukraine.
Trump imposed, then temporarily
reduced 20%
blanket duties on the EU’s U.S. exports to allow for negotiations. The bloc has
prepared its own counter-measures, but these were also put on hold after Trump
paused his own policies. It is also facing U.S. tariffs on aluminum, steel and
autos.
However, even if a deal is struck, the EU
is widely expected to still be impacted by some of the fallout from the ongoing
trade disputes between the U.S. and other trade partners like China.
European economic growth is expected to
suffer as a result of trade tensions, while the impact on inflation is murky to
say the least, European Central Bank policymakers told CNBC last
week during the IMF World Bank Spring Meetings, where “uncertainty” was the
name of the game.
“We have not seen this uncertainty now for
years,” said Robert Holzmann, governor of Austria’s central bank. “Unless the
uncertainty subsides, by the right decisions, we will have to hold back a
number of our decisions, and hence, we don’t know yet in what direction
monetary policy should be best moved,” he added in reference to the outlook for
ECB interest rates.
Klaas Knot, The Netherlands Bank
president, meanwhile compared the current
uncertainty to what was experienced during the early days of the Covid-19
pandemic.
“In the short run, it’s crystal clear that
the uncertainty that is created by the unpredictability of the tariff actions
by the U.S. government works as a strong negative factor for growth,” he said.
More
European Union
left reeling after Donald Trump's first 100 days
Port of Los Angeles says shipping volume will
plummet 35% next week as China tariffs start to bite
Published Tue, Apr 29 2025 9:23 AM EDT Updated
Tue, Apr 29 2025 11:10 AM EDT
Shipments from China to the West Coast of
the U.S. will plummet next week as the impact of President Donald Trump’s tariffs leads
companies to cut their import orders.
Gene Seroka, executive director of the
Port of Los Angeles, said Tuesday on CNBC’s “Squawk Box” that he
expects incoming cargo volume to slide by more than a third next week compared
with the same period in 2024.
“According to our own port optimizer,
which measures the loadings in Asia, we’ll be down just a little bit over 35%
next week compared to last year. And it’s a precipitous drop in volume with a
number of major American retailers stopping all shipments from China based on
the tariffs,” Seroka said.
Shipments from China make up about 45% of
the business for the Port of LA, though some transport companies will be
looking to pick up goods at other points in Southeast Asia to try to fill up
their ships, Seroka said.
“Realistically speaking, until some accord
or framework can be reached with China, the volume coming out of there — save a
couple of different commodities — will be very light at best,” Seroka said.
Along with the lower volume of goods,
Seroka said he expects roughly a quarter of the usual number of arriving ships
to the port to be canceled in May.
----Seroka said he thinks U.S.
retailers have about five to seven weeks before the impact of the curtailed
shipments begins to bite, partly because companies stocked up ahead of Trump’s
tariff announcements.
“I don’t see a complete emptiness on store
shelves or online when we’re buying. But if you’re out looking for a blue
shirt, you might find 11 purple ones and one blue in a size that’s not yours.
So we’ll start seeing less choice on those shelves simply because we’re not
getting the variety of goods coming in here based on the additional costs in
place. And for that one blue shirt that’s still left, you’ll see a price hike,”
Seroka said.
More
Port
of Los Angeles sees shipping volume down 35% next week as tariffs bite
“I learned that even though markets look their very best when they are setting new highs, that is often the best time to sell.”
Paul Tudor Jones
Global Inflation/Stagflation/Recession
Watch.
Given
our Magic Money Tree central banksters and our spendthrift politicians,
inflation now needs an entire section of its own.
Adidas
warns it will raise prices on all U.S. products due to tariffs
Published
Tue, Apr 29 2025 5:50 AM EDT
Sportswear
giant Adidas on Tuesday
said that U.S. President Donald Trump’s tariffs would result in price hikes for
all its U.S. products.
The
company said it did not yet know by how much it would boost prices, also noting
that the global trade dispute was preventing it from raising its full-year
outlook despite a bumper increase in first-quarter profits.
“Higher
tariffs will eventually cause higher costs for all our products for the US
market,” Adidas said in a statement.
The
company said it was “somewhat exposed” to White House tariffs on Beijing —
currently at an effective rate of
145% —
but that it had already reduced exports of its China-made products to the U.S.
to a minimum. However, it said the biggest impact was coming from the general
increase in U.S. tariffs on all other countries, which are largely held at
10% while
trade negotiations take place.
“Given
the uncertainty around the negotiations between the US and the different
exporting countries, we do not know what the final tariffs will be,” the Adidas
statement continued.
“Therefore,
we cannot make any ‘final’ decisions on what to do. Cost increases due to
higher tariffs will eventually cause price increases, not only in our sector,
but it is currently impossible to quantify these or to conclude what impact
this could have on the consumer demand for our products.”
Adidas
said it was currently unable to produce almost any of its products in the U.S.
The
company, best-known for sneakers including Superstar, Sambas, Stan Smiths and
Gazelles as well as sportswear, uses factories in countries including Vietnam and Cambodia — which are
facing U.S. tariffs upwards of 40% in the absence of a trade deal.
A
similar dilemma regarding price hikes and demand impact is facing almost all
retail businesses which serve the U.S., from ultra-low-cost
e-retailers like Temu to luxury giants such
as Hermès.
More
Adidas warns it
will raise prices on all U.S. products due to tariffs
HSBC
warns over possible hit from significantly higher global tariffs
29
April 2025
HSBC has warned
over a potential hit to revenues and rising bad debts in the event of
significantly higher tariffs worldwide as it posted lower quarterly profits and
forecast lending will remain muted in 2025.
The
UK’s largest bank, which is heavily exposed to Chinese and Asian markets,
said in the “plausible downside” scenario of surging tariffs, it could face a
“low single-digit percentage” impact on its revenues and around an extra 500
million US dollars (£372.8 million) in bad debts.
The
group increased its provisions for loans expected to turn sour by 202 million
US dollars (£150.7 million) year-on-year to 876 million (£653.4 million) in the
first quarter of 2025.
It
added that “given current levels of uncertainty and market turmoil, we expect
demand for lending to remain muted during 2025”.
The
comments came as it posted a 25% drop in pre-tax profit to 9.5 billion US
dollars (£7.1 billion) but this was better than expected by most analysts.
HSBC’s
quarterly revenue also decreased by 15% compared with quarter one of 2024, with
the company bringing in 17.6 billion dollars (£13.2 billion) for the same
period in 2025, but the fall in sales and profits was largely due to the impact
of disposals of businesses in Canada and Argentina.
The
bank is seen as having greater exposure to global trade disruption given its
operations across Asia.
But
it said it was yet to see any sign of customers defaulting in the face of the
trade war between America and China,
and US President Donald Trump’s sweeping 10% tariffs on goods entering America,
which caused chaos in stock markets around the world.
Chief
executive Georges Elhedery said: “We continue to support our customers through
this period of economic uncertainty and market unpredictability, which we enter
from a position of financial strength.”
He
added: “Ourselves and our customers as a whole are hopeful that we can see
progress in the trade negotiations between the US and a number of parties,
including China.”
He
said the group did not forecast the “end of globalisation, but a
reconfiguration of globalisation” where trading partner corridors “will
continue shifting geographically”.
More
HSBC warns over
possible hit from significantly higher global tariffs
The
student loan bubble is about to pop
As
collections resume after five years, disaster looms for delinquent borrowers.
April
29, 2025
At
the outset of the covid-19 pandemic, federal student-loan borrowers won what
appeared to be a reprieve. That five-year pause on payments and interest
accumulation is now shaping up to be a curse in disguise. Last week, the Trump
administration drew criticism for announcing that the Education
Department would resume involuntary collections next month. But
the squeeze delinquent borrowers will soon feel is an inevitable consequence of the
suspension, exacerbated by the Biden administration’s prolonged refusal to let
payments resume.
That’s
because nonpayment ballooned after the pause functionally ended last October,
meaning more than half of borrowers are not paying their loans on time. Data
provided to me by Nelnet, the largest student-loan servicer, offers a grim look
at repayment patterns.
In
February 2020, the last month before the government paused payments, 60 percent
of Nelnet’s borrowers were repaying their debts. Five years later, payments are
due again — but the repayment rate has fallen to 38 percent.
Some
of that drop results from the Education Department placing 8 million borrowers
in forbearance — a temporary postponement of payments — pending courts’
decisions on legal challenges to the Biden administration’s repayment plan.
But
even with this factored in, Nelnet’s data shows a spike in delinquencies
compared with before the pandemic. A staggering 15 percent of borrowers are
more than 90 days delinquent, which is reported to credit bureaus.
If
this wave of delinquencies continues, the Education Department has warned that 10 million borrowers — nearly a
quarter of the total — could be in default within a few months.
Reasons
for nonpayment vary, but many stem from the pause. Some borrowers are simply
unaware payments are due again — after all, the government extended the pause
eight times before quietly resuming payments in effect last fall. Others might
be bitter that the Biden administration failed to deliver loan forgiveness.
Millions more await the outcome of legal challenges to new loan repayment
plans.
Whatever
the reason, if borrowers remain delinquent, serious consequences await them. On
May 5, the government can resume seizing tax refunds or even garnishing
wages. Borrowers will also rack up more interest charges — paying more in the
long run — and suffer hits to their credit scores.
Though
high rates of delinquency have long been a problem, most borrowers who fell
behind on payments before the pandemic already had bad credit. That might change: Economists at
the New York Federal Reserve warn that borrowers with the best credit records have
the most to lose. The resulting credit score drops could prevent borrowers from
qualifying for home or business loans, impacting the broader economy.
More
Opinion | Biden’s student loan pause created a bubble. It’s about to pop. - The Washington Post
Covid-19
Corner
This
section will continue only occasionally when something of interest occurs.
Technology
Update.
With events happening fast in the
development of solar power and graphene, among other things, I’ve added this
section. Updates as they get reported.
This morning, something a little different.
Himalayan fungus compound tweaked for 40x anti-cancer boost
By Nick Lavars April 26, 2025
By using a compound derived from a Himalayan fungus and used for
centuries in Chinese medicine as a jumping off point, scientists have developed
a new chemotherapy drug with powerful anti-cancer effects. Doing so involved
chemically altering the compound to better infiltrate cancerous cells, which
proved to boost its potency by up to 40 times.
Editor's note: Readers often ask us for follow-ups on memorable
stories. What has happened to this story over the years? This article was
originally published in 2021 but has been re-edited and updated with new
information current as of April 25, 2025. Enjoy!
The 2021 research was carried out by
University of Oxford scientists in collaboration with biopharmaceutical company
Nucana, and began with a compound called Cordycepin. This naturally-occurring
nucleoside analogue has been used to treat inflammatory disease and cancer for
hundreds of years, but runs into several barriers that severely limit its
effectiveness when deployed to tackle tumors.
This is largely because as Cordycepin
enters the bloodstream, it is rapidly broken down by an enzyme called ADA. What
is left then needs to be carried into cancer cells by a nucleoside transporter,
and then converted into an anti-cancer metabolite called 3’-dATP. This is a lot
of hoops for the humble, naturally-occurring Cordycepin to jump through and
means only meager amounts wind up making it into the tumor.
NuCana looked to harness the anti-cancer potential of Cordycepin
and better equip it to navigate these considerable roadblocks, through what it
calls ProTide technology. This is designed specifically to address the
shortcomings of nucleoside analogues. It works by attaching small chemical
groups to the compound that make it more resistant to breakdown in the
bloodstream, and also enables them to enter cancer cells without the help of
nucleoside transporters. The upshot is that far greater levels of anti-cancer
metabolites are generated and activated inside tumor cells.
----When the research was published in the journal Clinical
Cancer Research back in 2021, the authors concluded that NUC-7738 had as
much as 40 times the potency of the naturally occurring Cordycepin, with
limited toxic side effects. The Phase 1 trial has since moved into the Phase 2
stage, involving a small number of patients with advanced solid tumors who had
"exhausted all treatment options."
The compound was combined with a checkpoint inhibitor called pembrolizumab for
this part of the NuTide:701 study, and NuCana presented final data at the ESMO
Congress in Barcelona last year. The patient cohort was made up of 12 patients
ranging from 42 to 74 years of age, who had all "received at least two
prior lines of PD-1 inhibitor therapy." The company reported that the drug
combination had managed to get the disease under control for nine of those
(75%), with a 55% reduction in tumor volume being noted in one patient. Seven
of the 12 "had a progression free survival time of greater than five
months, which is highly atypical in this patient population." And the
company reported a "favorable safety profile" for the cohort.
"The translational data that has been
generated in this study and in previous non-clinical studies give us confidence
that the effects we are seeing are a result of NUC-7738 making previously
resistant tumors sensitive to rechallenge with PD-1 inhibitors by targeting
multiple aspects of the tumor microenvironment," said NuCana founder and
CEO, Hugh S. Griffith in a press statement. A patent application was made in
September last year "covering NUC-7738’s composition of matter."
Encouraged by trial results over the last
few years, the company announced last month that Phase 2 trials involving a
larger cohort would commence some time in 2025, and that talks with the US Food
and Drug Administration are in the pipe to discuss the roadmap to approval.
Sources: University of Oxford,
NoCana [1,2,3]
Himalayan Fungus
Compound Tweaked for 40x Anti-Cancer Boost
Next, the
world global debt clock. Nations debts to GDP compared.
World Debt
Clocks (usdebtclock.org)
We at
Chrysler borrow money the old-fashioned way. We pay it back.
Lee Iacocca
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