Takeda Breaks Up With Denali, Dumps Dementia Drug

 

Takeda and Denali Therapeutics first partnered in early 2018 to advance drugs for neurodegenerative diseases. One asset, for Alzheimer’s disease, was previously discontinued after an FDA hold and disappointing early data.

More than eight years after linking up, Takeda and Denali Therapeutics are going their separate ways, with the Japanese pharma handing all rights to a dementia program back to Denali.

Takeda’s decision to terminate its partnership with Denali “was driven by strategic considerations,” the California biotech said in an SEC document dated April 3, and “is not related to efficacy or safety data.” The Japanese pharma informed Denali of its decision that same day, according to the securities filing.

The companies inked their partnership in January 2018, with Takeda fronting $150 million and promising unspecified milestone payments.

Takeda and Denali had also previously been working on the TREM2 agonist DNL919 for Alzheimer’s disease—but this molecule’s development path has been bumpy. In January 2022, the FDA slapped a clinical hold on the asset, though the partners at the time did not disclose why. The hold was eventually lifted, but Takeda and Denali in August 2023 nevertheless discontinued DNL919’s development, pointing to Phase 1 findings suggesting the drug had only a “narrow therapeutic window.”

In 2021, Takeda also exercised its option to co-develop and co-commercialize DNL593, a protein replacement therapy that can cross the blood-brain barrier, for frontotemporal dementia.

That asset has since been returned to Denali, the biotech said on April 3. “We are looking forward to advancing DNL593 independently,” CEO Ryan Watts said in a press statement that day, adding that the company “remain[s] confident” in the scientific rationale behind DNL593.

DNL593 works by replacing the progranulin protein, which in frontotemporal dementia is deficient, leading to lysosomal defects that, in turn, result in the accumulation of toxins across different tissues. The asset is currently in a Phase 1/2 study, enrollment for which has completed with 40 recruited participants, according to Denali’s April 3 release. There have been no reported safety signals to date, the biotech noted.

Phase 1/2 data for DNL593 are expected before the end of this year, Watts said.

Takeda’s pullback comes just days after Denali delivered a much-needed win for the rare disease space with the FDA approval of its Hunter syndrome therapy Avlayah. Like DNL593, Avlayah works by replacing a deficient player, this time targeting the IDS enzyme, which under healthy conditions clears toxic byproducts from several organs, including the brain.

Avlayah is the first Hunter syndrome therapy in nearly 20 years and is the first FDA-approved treatment to exploit the transferrin pathway to cross the blood-brain barrier.

https://www.biospace.com/deals/takeda-breaks-up-with-denali-dumps-dementia-drug

Iran rejects temporary ceasefire in 10-point response to US proposal

 

Iran has conveyed its official response to a US proposal to end the war through Pakistan after weeks of high-level deliberations, the government's news agency IRNA reported, saying Tehran rejected a ceasefire and instead called for a permanent end to the conflict on its own terms.

Iran’s response, which consists of ten points, was finalized following what IRNA described as “comprehensive reviews at the highest levels of the system.”

According to the report, Tehran rejected the idea of a temporary ceasefire, citing past experiences, and stressed the need for a lasting resolution to the war that takes into account Iran’s considerations.

The proposal outlines a set of demands, including an end to hostilities across the region, the establishment of protocols to ensure safe passage through the Strait of Hormuz, reconstruction efforts, and the lifting of sanctions.

IRNA said the response was delivered after developments over the weekend in western and central Iran, which it described as demonstrating Iran’s upper hand in the conflict.

The report also referred to what it called a “catastrophic failure” of a US heliborne operation and said US President Donald Trump had distanced himself from earlier threats by extending a repeated deadline.

https://www.iranintl.com/en/liveblog/202604067622

Gordon Chang: China could target US homeland if Iran conflict escalates

Unidentified, sophisticated drones flying over a handful of U.S. military bases could be a warning sign from China, Gordon Chang warned Monday, suggesting Beijing could target the American homeland if the U.S. becomes more involved in its conflict with Iran.

"The important point here is that we have had, last month, over four of our important military bases, foreign drones. These drones were large, they were un-hackable, they obviously were not recreational, so some foreign power — probably China, maybe Russia — was operating drones over our critical air force bases," Chang said on "Mornings with Maria." 

"Really, right now, the United States needs to be able to defend its bases in the homeland because those drone flights were a warning to the United States of some sort," he continued.

Chang suggested the drone activity could be an attempt to send President Donald Trump the message that, if U.S. forces escalate in the region, China could respond by potentially targeting bases on American soil.

That warning, coupled with a recent suspicious device left near MacDill Air Force Base in Florida — which Chang suggested may have been linked to China — highlights a growing threat, he warned.

"We've really got to be concerned," he said, later adding, "These are warnings that China intends to move on the U.S. in the American homeland."

Chang also warned that Beijing’s actions should be viewed in the context of its growing alignment with other U.S. adversaries like Russia and Iran, as tensions continue to spill across multiple global fronts.

"China is supporting Russia in Ukraine, and China is supporting Russia in other matters as well… So they have a durable partnership, and anything that helps one of them is going to generally help the other, with the exception of the matter that you just raised," he said, referring to the tension between higher oil prices benefiting Russia while raising costs for China.

"Generally speaking, the United States now faces a very powerful combination, and we shouldn’t be doing anything that fuels that combination," he added.

https://www.foxbusiness.com/media/china-could-target-us-homeland-iran-conflict-escalates-expert-warns

Iraq Tells Buyers To Collect Crude, Can Now Cross Hormuz, US Ups Ship Reinsurance Guarantees To $40B

 Over the long weekend, we reported that with traffic across the Hormuz strait continuing to rise, and reaching the highest since the war began, one particularly favorable development was Iran's permission for Iraqi ships to use the Strait. We also noted that this declaration had the potential to unleash as much as 3 million barrels a day of Iraqi oil cargoes.

That said, there was the caveat that it was not immediately clear if the exemption will apply to all Iraqi oil or just the nation’s tankers, or indeed how it will be enforced. Furthermore, an Iraqi official cautioned that the usefulness of the exemption will depend on whether shipping companies are willing to risk entering the strait to collect cargoes.

Today Iraq underscored this last point when the Gulf state told traders and refiners they can collect crude cargoes as vessels carrying the country’s oil are now able to transit the Strait of Hormuz thanks to an Iranian exemption, testing buyers’ confidence in the security guarantee.

In a notice sent on Sunday, the country’s State Organization for Marketing of Oil, known as SOMO, said Iraqi shipments were now “exempt from any potential restrictions,” citing media reports. 

It asked buyers for lifting schedules, including vessel details and volumes requested, adding all loading terminals including Basrah were “fully operational.” Customers were given 24 hours to respond.

As previously reported, Iran said over the weekend that its neighbor was now free from shipping restrictions around the vital waterway. The country’s military spokesman did not provide details on whether the arrangement applied to vessels or cargoes.

The Turkish-owned tanker Ocean Thunder, carrying a million barrels of Iraqi crude to Malaysia crossed the narrow waterway after the announcement.

As Bloomberg notes, Iraq often sells oil on a free-on-board (FOB) basis, meaning refiners sort out their own shipping, but it has struggled to export crude since the effective closure of Hormuz a month ago.

Asian buyers reached by Bloomberg said they were seeking clarity on conditions, including whether Iraq would offer the use of its own tankers, thereby providing extra security, although judging by Iraq's comments it is inviting buyers to send their own tankers. 

Separately, the Iraqi Basra Oil company announced that Iraq can restore oil exports to 3.4 million barrels per day within a week if Hormuz shipping resumed. 

Meanwhile, in hopes of kickstarting frozen traffic - and potentially taking over the lucrative shipping insurance market from London - on Friday the US announced it would double to $40 billion its commitment to provide reinsurance guarantees to ships willing to travel through the Strait of Hormuz with the addition of new insurance partners, including AIG and Berkshire Hathaway. The move was the latest US effort to ease worries over the vital waterway and to encourage traffic to resume.

Recall a month ago the US International Development Finance Corp. announced a $20 billion reinsurance program. On Friday, the agency said Travelers, Liberty Mutual Insurance, Berkshire Hathaway, AIG, Starr and CNA will join Chubb to provide an additional $20 billion in reinsurance for the agency’s maritime facility.

“Along with Chubb, these leading American insurers bring deep underwriting experience in marine and marine war coverage, strengthening our efforts to help restore confidence in maritime trade,” DFC Chief Executive Officer Ben Black said in a statement.

The DFC also said in the statement that the agency and insurance partners will determine which vessels are eligible for the reinsurance facility. To qualify, the DFC is requiring applicants to provide, among other details, the origin and destination country of the vessel; major beneficial owners of the ship and domicile; owner of the cargo and domicile of the owner; and information about the lenders financing the vessels.

Trump on Friday reiterated his frustration over the strait’s closure and the failure of allies to help the US reopen the waterway.

“With a little more time, we can easily OPEN THE HORMUZ STRAIT, TAKE THE OIL, & MAKE A FORTUNE,” Trump said in a social media post. It wasn’t immediately clear what actions the president was considering.

Shippers remain doubtful, though, of a wholesale return to the Strait of Hormuz even after Trump’s promise to protect ships and his primetime speech on Wednesday in which he repeated that the war will soon end. The key concern about traversing the sea route is that it puts the lives of crews at risk as Iran continues to threaten vessels with drone attacks, missiles and water mines.

https://www.zerohedge.com/military/iraq-tells-buyers-collect-crude-which-can-now-cross-hormuz-while-us-boosts-ship

Biogen - Expects Q1 2026 GAAP and non-GAAP EPS impact of $0.19 from charge

Biogen Inc. disclosed that its first-quarter 2026 results will include approximately $34 million in acquired in-process research and development, upfront and milestone expense on a pre-tax basis. This charge is expected to reduce GAAP and non-GAAP net income by about $0.19 per diluted share for the quarter ended March 31, 2026.

These expenses relate to collaboration and license agreements, including upfront and milestone payments and, when applicable, premiums on equity securities and asset acquisitions of in-process R&D. Biogen noted that quarterly results are preliminary and subject to closing procedures, and actual results may differ from current estimates.

https://www.stocktitan.net/sec-filings/BIIB/8-k-biogen-inc-reports-material-event-bc068d9a042d.html

Amgen Posts Strong Phase 3 Trial Data for Subcutaneous Tepezza

 Amgen reported positive results from its phase 3 trials of its thyroid eye disease treatment.

The biotechnology company said Monday that its under-the-skin version of Tepezza met its primary endpoints in treating moderate-to-severe thyroid eye disease, showing a 77% proptosis response rate, where there is a forward bulging of the eye, during the 24-week placebo-controlled period.

Thyroid eye disease is a rare autoimmune condition in which the body's immune system mistakenly attacks the tissues around the eyes.

Amgen said the effects of the subcutaneous version of the drug showed comparable results to the intravenous form of the medication.

Additionally, the company said the subcutaneous trial also showed strong improvements across many secondary measures of the disease, such as improvement for patients with double vision, called diplopia.

On the safety performance front, the company said the overall results were similar to its IV version.

https://www.morningstar.com/news/dow-jones/202604062444/amgen-posts-strong-phase-3-trial-data-for-subcutaneous-tepezza

ISM: US services activity declines in March

 The United States' service sector activity reported a decline in March, the Institute for Supply Management (ISM) revealed on Monday. The Services Purchasing Managers' Index (PMI) stood at 54%, down from February's 56.1% figure.

However, the New Orders Index improved, landing at 60.6%, compared to 58.6% in February. Suppliers Deliveries Index also rose, standing at 56.2%, while the Employment Index shrank to 45.2% from February's 51.8%.

"The predominant commentary this month was about impacts and adjustments due to the conflict with Iran and the expected flow through of higher oil prices at some point," the institute's Services Survey Committee Chair Steve Miller said, adding that "although tariff impacts were still noted by panelists, Iran-related impacts dominated the comments in March."

https://breakingthenews.net/Article/ISM:-US-services-activity-declines-in-March/66015214