GSK Dives Deeper Into Neuro With $2.5B+ ABL Bio Pact

 

GSK is paying to access ABL Bio’s Grabody-B platform, which potentially enables therapies to cross the blood-brain barrier.

GSK is fronting £38.5 million (nearly $50 million), in a partnership with South Korea’s ABL Bio to develop novel drugs for neurodegenerative diseases.

Aside from its upfront payment, GSK will also be on the hook for up to £2.075 billion ($2.66 billion) in research, development, regulatory and commercialization milestones, spread across the deal’s several potential programs. All told, the deal could mean more than a $2.5 billion windfall for ABL Bio.

At the center of Monday’s agreement is the South Korean biotech’s proprietary Grabody-B platform, which makes use of a novel targeting mechanism that allows bulkier therapeutic molecules to pass the blood-brain barrier.

According to the biotech’s website, ABL Bio’s approach leverages a bispecific antibody engineered to bind to the insulin-like growth factor 1 receptors, which are found on the cells that make up the blood-brain barrier, and in which turn allows the molecule to be shuttled across the barrier.

As per Monday’s deal, ABL Bio will transfer Grabody-B-related technologies and expertise to GSK. GSK will then be responsible for preclinical and clinical development, as well as taking charge of manufacturing and commercialization activities. ABL Bio will be entitled to tiered royalties on net sales of any product that results from this partnership.

GSK has not disclosed specific target indications, though Christopher Austin, senior vice president of Research Technologies, said in a prepared statement on Monday that the ABL Bio partnership is part of the pharma’s push to address “neurodegenerative brain diseases,” particularly those that are becoming more common “due to the aging of the population.”

GSK has pushed deeper into the neuro space in recent months. In December 2024, it paid $35 million upfront to partner with Danish biotech Muna Therapeutics to get access to its MiND-MAP platform.

GSK will be able to work on “multiple, high-value, validated” Alzheimer’s disease targets under the Muna partnership, though it hasn’t yet disclosed a specific number. For each target, Muna will be entitled to up to roughly $148 million in milestones.

In November 2024, GSK also partnered with Vesalius Therapeutics to leverage its proprietary platform, which according to Vesalius combines genomics, stem cells and AI, and use that platform to develop novel therapies for Parkinsons’s disease and another neurodegenerative disease. The pharma paid $80 million upfront and also pledged up to $570 in milestones for one preclinical program. Vesalius will also be entitled to undisclosed milestones and tiered royalties for each novel target.

https://www.biospace.com/business/gsk-dives-deeper-into-neuro-with-2-5b-abl-bio-pact

Stocks Quickly Wipe Out Losses as Bonds Tumble

 

Stocks halted a selling stampede as Wall Street traders sought signs of a bottom after a $9.5 trillion global wipeout that put the S&P 500 on the brink of a bear market.

The S&P 500 rose 3% on Monday, reversing an earlier slide of about 5%. Bonds erased their rally, but markets continued to price around 100 basis points in policy easing by the end of 2025- equivalent to four quarter-point cuts.

https://www.bloomberg.com/news/articles/2025-04-06/s-p-500-futures-slump-as-tariff-turmoil-deepens-markets-wrap

Niagen Says Its Operations Remain Resilient Amid Recent Tariff Developments

 Niagen Bioscience, Inc. (NASDAQ: NAGE) (formerly ChromaDex Corp.), the global authority on NAD+ (nicotinamide adenine dinucleotide) with a focus on the science of healthy aging, reaffirms that the manufacturing of its Niagen® ingredient (patented nicotinamide riboside or NR) and Tru Niagen® and pharmaceutical-grade Niagen® products remain resilient amid the recently enacted global tariffs.

Manufactured in the U.S. by the Company’s partner, W.R. Grace, Niagen is rigorously tested, encapsulated, bottled, and packaged domestically as Tru Niagen using premium materials. With only a small percentage of materials sourced internationally, the cost to manufacture final Niagen products remains largely insulated from global price volatility.

"We made the decision to build a U.S.-based supply chain for Niagen to safeguard long-term resilience, trust, and quality," said Rob Fried, CEO of Niagen Bioscience. "That foresight is proving valuable now. We remain confident in our ability to deliver Niagen products to customers and long-term stability to shareholders."

Currently, most vitamins—including nicotinamide riboside (NR)— remain exempt from the recently enacted tariffs. This exemption enables Niagen Bioscience to continue international operations without disruption. In 2024, approximately 24% of the Company’s revenue came from international sales, with over 12% attributed to A.S. Watson in Hong Kong—a duty-free market not subject to tariffs. As a result, this key international revenue stream remains unaffected by recent trade policy changes.

At this time, the Company anticipates no interruption in its ability to deliver Niagen products or maintain costs and pricing.

https://finance.yahoo.com/news/niagen-bioscience-confirms-operations-remain-123200897.html

CA Fails Audit Of Federal Programs, 66% Of COVID Unemployment Benefits In Question

 by Kenneth Schrupp via The Center Square,

California did not materially comply with the requirements for seven of the 22 federal programs the state auditor examined, including “pervasive” noncompliance in its unemployment benefits program, which could put essential federal funding at risk.

“This report concludes that the State did not materially comply with certain requirements for seven of the 22 federal programs or clusters of programs (federal programs) MGO audited, including one program for which the noncompliance was pervasive,” wrote Deputy State Auditor Linus Li.

“Additionally, although MGO concluded that the State materially complied with requirements for the remaining federal programs it audited, the State continues to experience certain deficiencies in its accounting and administrative practices that affect its internal controls over compliance with federal requirements.”

The audit found that even in 2023 — years after the state made $55 billion in fraudulent COVID lockdown-era benefits payments — the state likely made “potentially ineligible payments” of nearly $200 million. The audit also found that of 138 pandemic unemployment assistance claimants that were tested, 91, or 66%, had verification issues.

“While Gavin Newsom chases the national spotlight, Californians are left with an administration that can’t accomplish the basic functions of government,” said California State Assembly Minority Leader James Gallagher to The Center Square.

“The federal government is right to take a look at this spending and decide if it’s appropriate to keep throwing resources at an administration that treats it like Monopoly money.”

Last year, the state’s Legislative Analyst’s Office said the state’s unemployment fund runs a structural deficit of $2 billion per year, beyond the $20 billion debt and $1 billion in annual interest payments to the federal government. Because the unemployment fund is paid for by payroll taxes on employers and their employees, the LAO said payroll taxes would need to rise from $42 per employee making $46,800 or more per year, to $889.20, or over 21 times higher than the existing base payroll tax.

https://www.zerohedge.com/political/ca-fails-audit-federal-programs-66-covid-unemployment-benefits-question

When Keynesians Predict A Disaster, Start Buying

 by Daniel Lacalle,

I always get excited about a market correction when I read the Keynesian consensus predict a disaster. The same people who claimed massive money printing and soaring government spending wouldn’t cause inflation are the ones who know exactly how tariffs will impact aggregate prices. Fascinating.

In June 2016, sixteen Nobel Prize winners expected higher inflation from tariffs, and it never happened. Furthermore, many of those economists recommended enormous government spending and Federal Reserve quantitative easing in 2020, stating there were no concerns about inflation. However, this led to the highest inflationary burst in thirty years. Reality showed that there was no inflation in 2016-2019 and that the insane printing and spending spree of 2021 led to the current inflationary burst. This happens because many economic experts will always justify all government imbalances and tax hikes but raise alarm at any tax cut or supply-side measure. We should never trust experts that work painfully close to social democrat governments.

According to fearmongers, tariffs will create an enormous inflation burst both in the U.S. and abroad. These estimates show that Trump’s tariffs will be paid by US consumers, China tariffs against the US will also be paid by US consumers, and EU countermeasures will be paid only by American consumers. Quite amusing. If we believe this narrative, tariffs would be the best news for businesses all over the world: Americans would swallow the cost entirely, margins will not decline, and the world would be happy. It is so ridiculous that it would be laughable if millions did not take their words seriously. Furthermore, according to the consensus narrative, tariffs will cause a global recession if imposed by the US. However, when tariffs are imposed by China or the EU, then it is all fine.

When Keynesians predict a disaster, it is unlikely to happen. When the Keynesian consensus tells you that there is no risk, as they did in 2008, run away.

We should consider some relevant factors. Markets already discount a recession and a risk of stagflation, but the latest jobs report shows the opposite. 228,000 jobs were created in March despite some federal jobs. The ISM Composite Index points to expansion, and the economically weighted figure is comfortably above the expansion level (50) according to Real Investment Advice. All the investment and production leading indicators are far from a recession signal. Furthermore, many market participants seem to discount a hawkish Federal Reserve and a recession, something that has not happened in two decades.

What I find intriguing is that, for the first time in many years, the S&P 500 is attractively priced. After being hugely expensive in a bull market with constant multiple expansion, we can finally say that the S&P 500 is starting to be attractive, even if you discount a significant downward revision in earnings. The Price-to-Earnings ratio of 15.2x for 2027 provides ample room for a revision and still shows an attractive entry point. Stocks are quite cheap at 10.3x EV to EBITDA 2027 (enterprise value to earnings before interest, taxes, depreciation, and amortisation). Furthermore, with the 10-year yield of Treasuries at 3.99%, it means that stocks look attractive compared to bonds for the first time in months. Margins are strong, guidance is positive, and entry points for long-term investors are starting to be evident, as inflationary pressures are likely to be limited and the so-called trade war will be negotiated, with more than 50 nations calling on the US government to make a deal on trade barriers.

Any long-term investor should look at opportunities in which fear is exaggerated, valuations are attractive, and consensus concerns are unrealistic. It may be a good idea to start building long positions, knowing that quantitative easing and rate cuts will likely follow periods of volatility.

Investors need to protect themselves against inflationism and central bank destruction of the purchasing power of currency and that has not gone away; it is coming back stronger as governments all over the world continue to build debt and fiscal imbalances. Protect yourself against inflation with a balanced strategy, building positions that protect your wealth and help you navigate volatility.

https://www.zerohedge.com/markets/when-keynesians-predict-disaster-start-buying

7 Late-Stage MASH Candidates That Could Reshape the Market

 

Akero Therapeutics, 89bio, Boston Pharmaceuticals and more are working to bring novel treatment options for metabolic dysfunction-associated steatohepatitis to a market that could reach $16 billion by 2033.

It’s been a little more than a year since the FDA approved Madrigal Pharmaceuticals’ Rezdiffra as the first treatment for the liver disease metabolic dysfunction-associated steatohepatitis. After earning $180 million in full-year 2024 sales, Madrigal expects Rezdiffra to reach blockbuster status in the coming years.

With an estimated 22 million Americans living with metabolic dysfunction-associated steatohepatitis (MASH)—previously known as nonalcoholic steatohepatitis (NASH)—there is a growing pipeline of potential therapies, and several companies are expecting Phase III readouts in 2025. Rather than relying on one strategy, the leading candidates are approaching the disease from different angles. This could allow more assets to carve out a share of a market that is expected to be worth $16 billion by 2033.

Rezdiffra’s early success, along with clinical research suggesting that GLP-1 drugs could also have therapeutic potential in MASH, has analysts optimistic about the growth potential of the space.

“That’s why Rezdiffra has been so heavily watched and why there are so many drugs in development for MASH,” Edward Nash, senior biotechnology analyst at Canaccord Genuity, told BioSpace. “It’s thought of as having the potential to be the next type 2 diabetes for the industry. It’s that big of a metabolic disease, and it offers multi-billion dollar opportunities for many different treatment mechanisms.”

Here, BioSpace looks at five candidates that could soon emerge on the market.

89bio’s Pegozafermin

Fibroblast growth factor 21 analog

Currently undergoing Phase III trials, 89bio’s pegozafermin is part of a class of treatments for MASH that mimics the activity of fibroblast growth factor 21 (FGF21), a hormone produced by the liver that acts as a metabolic regulator. According to Nash, FGF21 analogs have generated the most attention because they’ve shown a “really strong ability to reduce liver fibrosis,” which is damage to the liver caused by the chronic inflammation associated with MASH.

So far, pegozafermin is no exception. Phase IIb trial results showed the candidate managed at least one-stage fibrosis improvement at two different dosage levels (30 mg weekly and 44 mg every-other week) without worsening of MASH. In addition, MASH resolution without worsening of fibrosis was managed at 26% and 23%, dependent on the dosage.

Rohan Palekar, CEO of 89bio, pointed to a recent peer-reviewed publication where pegozafermin was ranked as the most efficacious drug for fibrosis improvement and MASH resolution among all approved or investigational MASH drugs. “A key distinction is that pegozafermin has also shown a favorable safety and tolerability profile, with few gastrointestinal side effects and no clinically significant effect on bone density,” Palekar told BioSpace in an email.

Akero Therapeutics’ Efruxifermin

Fibroblast growth factor 21 analog

Akero finds itself in a similar position to 89bio, with a FGF21 analog in Phase III trials. However, the biotech’s path to this point, at least from a shareholder perspective, has been more tumultuous. Akero’s stock price sunk in October 2023 after efruxifermin missed its primary endpoint of 36-week fibrosis improvement in a Phase IIb trial. The drug’s prospects were saved five months later when the biotech was able to show in 96-week data that fibrosis was significantly improved in patients with MASH.

“Unlike other MASH drugs that target [a] specific pathway, efruxifermin delivers sustained FGF21 signaling to both liver and adipose tissue, aiming to correct metabolic imbalances that drive disease progression,” Kitty Yale, chief development officer at Akero, told BioSpace over email. “While some obesity drugs aid weight loss, they may not directly target the liver, limiting their impact on fibrosis.”

The biotech has a Phase III program comprising three ongoing clinical trials aimed at supporting future regulatory applications of efruxifermin for patients with compensated cirrhosis due to MASH and with pre-cirrhotic MASH, Yale added.

Boehringer Ingelheim, Eli Lilly, Novo Nordisk: Survodutide, Tirzepatide, Semaglutide

GLP-1 agonists

A fierce competition is underway between weight loss rivals, as GLP-1 drug developers attempt to differentiate their treatments. One strategic angle has been to target MASH as an additional indication to support the drugs’ widespread use. According to Nash, an approval in MASH would boost GLP-1s’ appeal for physicians because it would allow them to address three metabolic diseases—type 2 diabetes, obesity and MASH—with the same treatment.

Boehringer Ingelheim, Eli Lilly and Novo Nordisk have all adopted this approach. Boehringer and Novo Nordisk have progressed survodutide and semaglutide, respectively, through to Phase III trials, and Lilly posted positive Phase II trial results for tirzepatide in June 2024. Of the GLP-1s currently being studied for MASH, Nash suggested that semaglutide is the closest to potential FDA approval, projecting that an approval could come by the end of 2025 or in the early part of 2026.

While clinical trials have indicated that GLP-1s can reduce fat in the liver, that does not necessarily indicate that fibrosis will also be reduced, Nash cautioned. Due to this limitation, GLP-1 drug developers will likely explore combination therapies, which could see other approaches to MASH combined with GLP-1 medicines, he added. Both Palekar and Yale said they are exploring using their MASH candidates in conjunction with GLP-1s.

Boston Pharmaceuticals’ Efimosfermin Alfa

Fibroblast growth factor 21 analog

Boston Pharmaceuticals’ FGF21 analog is a little bit different. A fusion protein based on human IgG and FGF21, efimosfermin alfa is longer-acting than other late-stage rivals in the MASH pipeline, with Boston exploring a once-monthly regimen for the drug. In November 2024, the potential treatment elicited a one-stage improvement in fibrosis without worsening of MASH in a Phase II trial. The biotech plans to advance efimosfermin into Phase III trials in the fourth quarter of this year, according to CEO Sophie Kornowski. Similar to other companies working in the space, the next stage of trials will assess how efimosfermin pairs with incretin treatments for diabetes, such as GLP-1s, Kornowski told BioSpace via email.

Nash likened Boston’s dosing to approaches in immunology and inflammation, where when rival drugs’ clinical outcomes are similar and the longer dosing schedule drugs are preferred. Margaret Koziel, chief medical officer at Boston, told BioSpace by email that efimosfermin’s increased half-life is enabled by “several point mutations and an additional disulfide bond that prevents proteolytic degradation.”

Viking Therapeutics’ VK2809

Thyroid hormone receptor agonist

Adopting a similar approach to Madrigal, Viking has a thyroid hormone receptor agonist as its lead candidate for MASH. The biotech posted positive Phase IIb data in November 2024 showing that up to 75% of patients treated with VK2809 reached MASH resolution without fibrosis worsening. A further 57% showed at least a one-stage improvement in fibrosis without deterioration of MASH.

Like Rezdiffra, VK2809 is a small molecule, oral treatment. In Phase II studies, Viking carried out both a daily and an every-other-day dosing schedule. In full-year results released in February 2025, Viking stated that it considered its drug candidate “best-in-class” but only noted that it is “currently evaluating potential next steps” for VK2809. Should the development of VK2809 prove successful, the biotech could explore trialing the treatment alongside its own GLP-1 treatment candidate, VK2735, providing Viking with an in-house combination therapy.

Despite this healthy roster of candidates, Nash said it is unlikely that any of them will be able to fully displace Rezdiffra. “Given their lead over the competitive landscape and being on the market first, Madrigal is going to have entrenched itself by the time competitors arrive,” he concluded. “Plus, it’s a safe drug—so, it’s a nice, solid foundational drug to have on the market.”

https://www.biospace.com/drug-development/7-late-stage-mash-candidates-that-could-reshape-the-market

Hamas fires rockets at Israeli cities, Israel issues evacuation orders in Gaza

 Palestinian militant group Hamas said it fired a barrage of rockets at cities in Israel's south on Sunday in response to Israeli "massacres" of civilians in Gaza.

Israel's military said about 10 projectiles were fired, but most were successfully intercepted. Israel's Channel 12 reported a direct hit in the southern city of Ashkelon.

Israeli emergency services said they were treating one person for shrapnel injuries, and teams were en route to locations of fallen rockets. Smashed car windows and debris lay strewn on a city street, videos disseminated by Israeli emergency services showed.

Meanwhile, Gaza local health authorities said Israeli military strikes killed at least 39 people across the Gaza Strip on Sunday.

Shortly after the rocket firing, the Israeli military posted on X a new evacuation order, instructing residents of several districts in Deir Al-Balah city in the central Gaza Strip to leave their areas, citing earlier rocket firing.

"This is a final warning before the attack," the military warning statement said.

Later, it said it struck the rocket launcher from which projectiles were launched earlier from the Gaza Strip.

Israeli Prime Minister Benjamin Netanyahu, on a flight to Washington for a meeting with U.S. President Donald Trump, was briefed on the rocket attack by his Defense Minister, Israel Katz.

A statement issued by his office said Netanyahu instructed that a "vigorous" response be carried out and approved the continuation of intensive activity by the Israeli military against Hamas.

Israel's Channel 12 television said at least 12 lightly injured people have been treated as a result of the rocket firing from Gaza, quoting officials at the Bazilai Hospital in Ashkelon.

The first phase of a ceasefire between Israel and Hamas went into force on January 19 after 15 months of war and involved a halt to fighting, the release of some of the Israeli hostages held by Hamas, and the freeing of some Palestinian prisoners.

However, Israel said on March 19 that its forces resumed ground operations in the central and southern Gaza Strip. Both parties blamed one another for a stalemate in the ceasefire talks.

More than 50,000 Palestinians have been killed by the Israeli offensive in Gaza, Palestinian officials say.

Israel began its offensive after thousands of Hamas-led gunmen attacked communities in southern Israel on October 7, 2023, killing 1,200 people and abducting 251 as hostages, according to Israeli tallies.

https://www.yahoo.com/news/hamas-fires-rockets-israeli-cities-192050494.html