'DHS warns of risks around Oct. 7, November election in annual threat assessment'

 The 2024 election and the ongoing conflict in the Middle East are among the elements contributing to a high threat level in the U.S. going into 2025, the Department of Homeland Security (DHS) concluded in its annual threat assessment.

The report falls just days ahead of the first anniversary of the Oct. 7 attack Hamas carried out in Israel, sparking a war that has now expanded across the region.

“We are, of course, aware that that anniversary may add even more fuel to an already challenging and heightened threat environment,” a DHS official said on a call with reporters.

The official noted the risk to the Jewish and Muslim communities, citing expansion of the conflict into Lebanon and Iran’s recent strike against Israel.

“All of these factors contribute to a heightened threat environment, because at times, they are motivating factors that drive particular violent extremist groups to accelerate or plan to take action on a timeline that may not have been anticipated,” they added.

The annual assessment is otherwise in line with other long-term trends seen in the U.S.

Lone wolf actors and small groups continue to present the greatest terror risk within the U.S., influenced both by domestic and international developments.

“Over the next year, the terrorism threat environment in the Homeland will remain high. We are particularly concerned about a confluence of factors this year, including violent extremist responses to domestic sociopolitical developments — especially the 2024 election cycle — and international events that domestic and foreign violent extremists likely will use to justify or encourage attacks,” the report concluded. 

China, Russia and Iran remain among the U.S.’s greatest adversaries and most likely to target critical infrastructure as well as seek to undermine U.S. elections.

The three nations “will use a blend of subversive, undeclared, criminal, and coercive tactics to seek new opportunities to undermine confidence in US democratic institutions and domestic social cohesion,” the report states.

“Most concerningly, we expect the PRC [People’s Republic of China] to continue its efforts to pre-position on US networks for potential cyber attacks in the event of a conflict with the United States.”

The report builds on a series of warnings from the intelligence community about the trio’s election activities as well as various recent indictments handed down by the Justice Department.

That includes bringing charges against two RT employees, formerly known as Russia Today, for partnering with Tenet Media to pay influencers to promote Russia-backed narratives as well as the seizure of 32 fake news sites run by Russia.

The Department of Justice also recently indicted multiple Iranian operatives for hacking former President Trump’s campaign and attempted to disseminate the stolen materials.

Beyond influence efforts, the report warns of possible attacks, including violent ones against election officials, and the DHS official likewise warned countries could try and spread disinformation about voting processes, such as falsely claiming elections have been rescheduled.

It also references the assassination attempts against Trump, including a plot by Iran, saying the incidents “highlight the magnitude of the threat surrounding the election cycle.”

At the southern border, the report touts an increase in fentanyl seizures and a decline in recent border crossing figures, a trend ignited this summer as the Biden administration rolled out new limitations on seeking asylum.

The number of migrants flagged under the terror watch list has also risen and fallen in line with broader migration trends.

A DHS official noted, however, that the U.S. has seen shifts in the nationalities of people arriving at the border, with many beyond the western hemisphere now arriving in Latin America to then attempt to cross the border.

“Now, our border personnel encounter individuals from around the world, from all parts of the world, to include conflict zones and other areas where individuals may have links or can support ties to extremist or terrorist organizations that we have long standing concerns about,” the official said.

https://thehill.com/policy/national-security/4912052-dhs-oct-7-november-election-risk-assessment/

Musk sending more Starlink terminals to storm-ravaged North Carolina

 SpaceX CEO Elon Musk said Tuesday the aerospace company is sending more Starlink terminals to North Carolina following the widespread devastation of Hurricane Helene.  

“Since the Hurricane Helene disaster, SpaceX has sent as many Starlink terminals as possible to help areas in need,” Musk wrote in a post on the social platform X. “Earlier today, @realDonaldTrump alerted me to additional people who need Starlink Internet in North Carolina. We are sending them terminals right away.” 

Former President Trump, who said he spoke with Musk earlier this week about providing Starlink internet service, lauded Musk for the assistance.  

“Great news. So badly needed in North Carolina, where there is virtually no communication. Starlink was the perfect answer, and Elon Musk, as usual, came through. Thank you Elon!!! DJT” Trump wrote on Truth Social overnight Wednesday.  

There are 40 Starlink satellite systems available in North Carolina to help with responder communications, and an additional 140 satellites are being shipped to assist with communications infrastructure restoration, the White House said earlier this week. One Starlink will be deployed for every county’s emergency operations center to help with communications. 

Helene made landfall last Thursday in Florida as a Category 4 hurricane, bringing heavy winds and rainfall to multiple states across the south. At least 166 people have been killed, The Associated Press reported, and millions have been left without power.  

More than 1.2 million customers still had no power Wednesday in the Carolinas and Georgia, where the hurricane ravaged several inland areas in the states.  

Trump visited Georgia on Monday to tour storm damage and expressed support for those dealing with the aftermath. He indicated he will also visit North Carolina.  

https://thehill.com/policy/technology/4911419-musk-starlink-help-north-carolina/

'HHS expecting ‘limited’ impact on drug supply chain from port strike'

 The Department of Health and Human Services (HHS) is not anticipating a major impact on the availability of health care products stemming from the port strike that began this week, with current assessments foreseeing a “limited” effect.

Members of the International Longshoremen’s Association (ILA) went on strike Tuesday after bargaining talks with the U.S. Maritime Alliance failed to reach an agreement, with the issue of increased compensation being a particular sticking point.

The strike has the potential to drastically shake up the U.S. economy, potentially costing as much as $5 billion per day.

But after meeting with “trade associations, distributors, manufacturers, and other stakeholders,” the HHS said it isn’t expecting a major effect on medical supply chains.

“Current preliminary assessments indicate immediate impacts across medicines, medical devices, and infant formula for consumers, parents, and caregivers should be limited. The Administration is taking action to monitor and address potential impacts on consumers of labor disputes at East Coast and Gulf Coast ports,” HHS said in a statement.

“ASPR [Administration for Strategic Preparedness and Response] and FDA [Food and Drug Administration] have and will continue working closely with HHS to quickly identify potential shortages of lifesaving products impacted by a strike to determine the cause and work with manufacturers and distributors to address local, regional and national needs as they arise,” the statement continued, adding that the administration supported both parties coming back to the bargaining table “fairly and quickly.”

According to the American Hospital Association, the U.S. increasingly relies on foreign countries for medical supplies, devices and equipment, especially from China. The U.S. has imported roughly $15 billion in medical equipment this year.

https://thehill.com/policy/healthcare/4912018-port-strike-hhs-medical-supply-chain-drug-availability/

Novavax stock rallies 15% following bullish Jefferies note

 Novavax (NVAX) shares climbed 15% Wednesday after Jefferies released a bullish note on the company's prospects after meeting with management.

https://seekingalpha.com/news/4155671-novavax-stock-rallies-following-bullish-jefferies-note

Liquidia, Pharmosa Expand Pact to Develop Sustained Release Inhaled Treprostinil

 

• Liquidia amends exclusive license to include key markets in Europe, Japan and elsewhere
• Liquidia also obtains rights to Pharmosa’s next-generation nebulizers for use with L606
• Pharmosa to receive $3.5 million upfront and up to $157.75 million in additional development and sales milestones tied to commercial sales outside of North America

https://www.globenewswire.com/news-release/2024/10/02/2956774/0/en/Liquidia-and-Pharmosa-Biopharm-Expand-Collaboration-to-Develop-Sustained-Release-Inhaled-Treprostinil-L606.html

The Making of BMS’ Cobenfy: From Alzheimer’s to Schizophrenia

 

From Eli Lilly to Karuna Therapeutics to current owner Bristol Myers Squibb, the newly approved schizophrenia drug had quite the journey to market. Former Karuna and Lilly executives discuss the “accidental” and “serendipitous” discovery.

What began as a therapeutic candidate for Alzheimer’s disease at Eli Lilly completed its development journey Thursday in the hands of Bristol Myers Squibb as Cobenfy, the first novel treatment for schizophrenia in 35 years. Andrew Miller, former CEO of Karuna Therapeutics who co-invented the drug, said this trajectory is not uncommon in neuropsychiatric diseases.

“The only treatments we have for schizophrenia was because chlorpromazine, which was an anesthetic drug in the ’50s, was discovered to have antipsychotic effects . . . and that was kind of the parent of all of the currently available treatments for schizophrenia,” Miller told BioSpace. Similarly, he added, the first approved treatment for depression was an anti-tuberculosis medicine.

“When you look at the history of psychiatric drug development, the source of innovation, in many respects, is serendipitous, human to human findings,” Miller said.

Weight Loss Rivals Were Once Alzheimer’s Partners

In the mid-1990s, Lilly and current obesity and diabetes archrival Novo Nordisk were collaborating on a muscarinic acetylcholine receptor stimulator agonist to treat cognitive impairment in Alzheimer’s disease. Acetylcholine is the neurotransmitter through which cholinergic neurons, which are involved in memory and learning, send their messages.

People with Alzheimer’s lose these neurons early in the disease process, said Steven Paul, who oversaw the program at Lilly. “So, our idea in those days was if we could stimulate the receptors for acetylcholine, maybe in the absence of those neurons we could still enhance memory and learning,” Paul told BioSpace. This idea birthed xanomeline, an acetylcholine receptor agonist that the partners studied in a large Phase II trial.

The results showed xanomeline had a “modest” but “significant” effect in improving memory, Paul said. However, the trial also revealed adverse events such as nausea, vomiting and excess salivation—effects associated with stimulating muscarinic receptors. Ultimately, the companies made the decision not to proceed with xanomeline “because we felt we didn’t have the requisite tolerability safety margin for patients with Alzheimer’s,” Paul said.

But, as part of the trial, the companies had also studied xanomeline’s effect on “abnormal behaviors” in Alzheimer’s such as hallucinations and delusions. “The drug seemed to treat these psychotic symptoms, and it seemed to prevent the emergence of these psychotic symptoms in these patients,” Paul said. With the exception of the adverse events, “that was the most striking finding.” Paul and colleagues published their findings in a 1997 paper.

“This was by accident,” Paul said. “We didn’t really think this might happen.”

A few years later, researchers at Lilly wondered if these same effects might translate to patients with schizophrenia. To answer this question, the company conducted a small study at Indiana University. “And sure enough, the drug seemed to work in those patients as well,” Paul said. But the adverse effects remained, and the companies did not pursue this indication either.

KarXT Is Born

Enter PureTech Health, where Miller, who was vice president in 2009, had an idea: Instead of tweaking xanomeline for more selectivity and fewer side effects—which Paul said “probably wasn’t going to work anyway”—why not combine it with a muscarinic antagonist molecule that blocks the peripheral side effects while leaving efficacy unaffected?

In 2009, PureTech founded Karuna Pharmaceuticals, which later changed its name to Karuna Therapeutics, to take the candidate forward, with Miller at the helm.

“It took a lot of effort to get from that concept to the actual, real matter of KarXT,” Miller said. Perusing the scientific literature, Karuna identified 65 muscarinic acetylcholine receptor agonist molecules and 114 muscarinic antagonist molecules. “So that gives you 7,410 possible combinations.”

Ultimately, Karuna selected 95 parameters, some specific to the agonist molecule, others specific to the antagonist, and still others about how combinations would function. At the end of this process, the researchers stuck with xanomeline as the agonist and selected trospium as the antagonist, and the combination became KarXT.

Interestingly, “[Karuna] couldn’t raise any money. There was very little interest,” said Paul, who joined the company as CEO in 2018 after Karuna published Phase I data. “Sometimes these are the best companies, when people turn you down.”

The Phase I trial, in which 70 healthy volunteers received either KarXT or xanomeline plus placebo, showed a significant difference in terms of side effects: 64% of patients in the xanomeline/placebo group saw the most common xanomeline-associated side effects vs. 34% in the KarXT cohort.

These early results generated some excitement. In 2018, Karuna raised $42 million in a Series A round, followed six months later by a $68 million Series B, which was later topped up to $80 million. That same year, Paul and Miller took the company public. Then, in November 2019, KarXT met the primary efficacy endpoint in the Phase II EMERGENT-1 trial, where it was also found to be generally well-tolerated, “and our stock just went off the roof,” Paul said. According to Biopharma Dive, Karuna’s value increased from around $400 million to nearly $3 billion following this data drop.

BMS Buys Karuna for $14B

By December 2023, Karuna had two successful Phase III trials under its belt, and BMS came knocking. Paul said they’d actually been in discussions with BMS since the J.P. Morgan Healthcare Conference in January 2023 but it wasn’t until the company submitted the New Drug Application for KarXT in September 2023 that the pharma company was ready to commit to buying Karuna.

“I presented to them the story, and we didn’t hear from them afterwards until later that year,” Paul said. “Then, once we filed the NDA with the FDA, we had them and another company kind of beating down our door.”

While Paul wouldn’t reveal the name of the other suitor, he did say that Karuna had “narrowed it to a bit of a bake-off with those two companies.”

Prior to agreeing to the buyout deal with BMS, Paul said Karuna had intended to launch KarXT itself. “We were building a sales force. We were building a commercial presence.”

In the end, however, Karuna decided BMS’ offer was in the best interest of its stakeholders. “When I joined the company, as a private company of maybe $20- $30-, $40 million bucks . . . we went public, and maybe we were worth at most $400 [million]. And then we were offered $14 billion dollars for the company, in less than five years.”

He called the decision bittersweet “because if the drug had been approved, if we had ourselves commercialized it, if it became a mega billion-dollar blockbuster drug ourselves, well, the company’s value would be much greater than $14 billion dollars.”

Paul calls KarXT “one of my early children” and said he is pleased with its progress. “They’re [BMS] doing a great job with it, so far as I can tell,” he said.

While BMS is starting with schizophrenia, KarXT/Cobenfy’s journey may be far from over. A recent post-hoc analysis showed that a subset of patients in the pivotal Phase III EMERGENT-1 and EMERGENT-2 studies with predominantly negative symptoms of schizophrenia—such as apathy and social withdrawal—at baseline saw a larger effect on negative symptoms than the overall trial population. And the drug may also treat the disease’s cognitive symptoms, including poor memory and low attention span, said Paul, adding that another paper on this was recently accepted for publication.

In a return to its roots, BMS has also shared plans to test Cobenfy in Alzheimer’s disease psychosis, as well as bipolar disorder. “Our expectation is that KarXT is our first foray into schizophrenia and serious mental illnesses,” Carlos Dortrait, SVP and general manager of U.S. immunology and neuroscience at BMS, previously told BioSpace, “but we are looking at expanding and looking very broadly across many diseases.”

https://www.biospace.com/drug-development/the-making-of-bms-cobenfy-from-alzheimers-to-schizophrenia

Biden Scolds Ocean Carriers For Not Paying Dockworkers "Fair" Wages

 By John Gallagher of FreightWaves

President Joe Biden broke his silence on the labor dispute between the International Longshoremen’s Association (ILA) and the United States Maritime Alliance (USMX) by accusing employers of hoarding profits.

“Ocean carriers have made record profits since the pandemic and in some cases profits grew in excess of 800 percent compared to their profits prior to the pandemic,” Biden said in a statement issued by the White House on Tuesday, after the ILA went on strike at 14 ports on the U.S. East and Gulf coasts, halting container and roll-on/roll-off operations at 36 marine terminals.

“Executive compensation has grown in line with those profits and profits have been returned to shareholders at record rates. It’s only fair that workers, who put themselves at risk during the pandemic to keep ports open, see a meaningful increase in their wages as well.”

In urging USMX to the bargaining table with an acceptable wage offer, Biden also warned the carriers against taking advantage of supply chain disruptions caused by Hurricane Helene.

“As our nation climbs out of the aftermath of Hurricane Helene, dockworkers will play an essential role in getting communities the resources they need. Now is not the time for ocean carriers to refuse to negotiate a fair wage for these essential workers while raking in record profits.

“My administration will be monitoring for any price gouging activity that benefits foreign ocean carriers, including those on the USMX board.”

Among USMX members are foreign-based container ship operators CMA CGM (France), Maersk (Denmark), Cosco (China), MSC (Switzerland), OOCL (Hong Kong) and Evergreen (Taiwan).

The compounding effect of the strike and disruptions caused by the hurricane is raising transportation fears among food producers and retailers.

“There’s never a good time for a strike,” said Food Industry Association President and CEO Leslie Sarasin in a statement on Tuesday.

“Now, the current strike is compounding the horrific situation in the Southeastern United States resulting from Hurricane Helene and parties need to return to the negotiating table.

“This action has already begun to jeopardize food supply chain operations, and the strike has the potential to disrupt the long-term stability of markets and commodities, namely pharmaceuticals, seafood, produce, meat, cheese, ingredients, and packaging.”

White House Press Secretary Karine Jean-Pierre told reporters on Tuesday that the strike is not yet hindering relief and recovery efforts related to the hurricane because emergency supplies had been positioned ahead of the storm.

She said the administration has stood up the Supply Chain Disruptions Task Force, created by the White House in 2021 in the wake of the pandemic, to monitor the situation.

“We are engaged extensively with labor, industry, state and local officials, ocean carriers, rail and truck companies, including multiple meetings with retailers, grocers, manufacturers, and agriculture,” Jean-Pierre said. “We are assessing ways to address any concerns, if necessary.”

On whether that would include ordering the union workers back to work by invoking the Taft-Hartley Act, “We have not used Taft-Hartley and we’re not planning to,” she said.

https://www.zerohedge.com/economics/biden-scolds-ocean-carriers-not-paying-dockworkers-fair-wages