South Korea holds emergency meeting as EV fires stir consumer fear

 South Korean officials met on Monday to discuss electric vehicle safety and whether to require car firms to disclose battery brands amid growing consumer concern after an EV blaze in an underground garage extensively damaged an apartment block.

The fire on Aug. 1, which appeared to start spontaneously in a Mercedes-Benz EV parked below a residential building, took eight hours to put out, destroying or damaging about 140 cars and forcing some residents to move to shelters.

The country's vice environment minister is leading the meeting, which is also being attended by the transport and industry ministries and the national fire agency, an official said, with the government due to announce new rules soon.

On Tuesday, transport ministry officials will hold talks with automakers, including Hyundai Motor Group, Mercedes-Benz Korea and Volkswagen Group Korea, to discuss the proposal to disclose battery brands used in EVs, media reports said.

The ministry did not immediately provide a comment on the reports. Hyundai Motor Group, Mercedes-Benz Korea and Volkswagen Group Korea did not immediately respond to a request for comment.

Images published in media of dozens of charred cars with only their metal frames remaining in the parking lot fire have fuelled consumer fears about EVs, likely exacerbated because so many people in South Korea live in apartments, often with parking lots below.

Early this month, Kia Corp's electric crossover EV6 with South Korean battery maker SK On's batteries also caught fire in a parking lot, fire authorities said.

Car experts say that EVs burn differently to cars with internal combustion engines, with fires often lasting longer and harder to extinguish as they have a tendency to reignite.

The Seoul Metropolitan Fire & Disaster Headquarters in a report published in February said 1,399 fires occurred in underground parking lots in South Korea between 2013 and 2022, with 43.7% attributed to vehicles. It said electrical sources accounted for 53% of car fires in underground garages.

The Chosun Ilbo newspaper reported last week that South Korea planned to require EV makers to disclose the brand of batteries in cars.

Automakers currently need to provide certain information about vehicles, such as fuel efficiency, but only limited details on batteries and do not have to name the manufacturers, the newspaper said.

On Saturday, Hyundai Motor Co identified manufacturers of batteries used in their 13 EV models, including three models from its Genesis brand on its website, after receiving many enquiries about EV battery makers.

https://finance.yahoo.com/news/south-korea-holds-emergency-meeting-044530753.html

5 Obesity Readouts to Watch in the Second Half of 2024

 

Hundreds of companies are currently running clinical trials in the increasingly lucrative obesity space. BioSpace looks at five candidates with data expected before the end of the year.

With a quarter of the world’s population expected to have obesity by 2035 and the market for obesity therapeutics predicted to hit $131 billion within the next five years, it’s no wonder the disease is one of biopharma’s hottest targets. While the space is currently dominated by Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound, several other candidates are making their way through the pipeline, their makers aiming to snag a piece of the lucrative pie.

While the efficacy of the GLP-1 class of medicines for obesity is well-documented, Graig Suvannevejh, senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas, noted that there are still unmet needs. In an interview with BioSpace, he put future developments into four categories: drugs that have better safety and tolerability, those that can elicit greater weight loss, oral options instead of today’s injectables and therapies that are muscle-sparing.

Several companies—Novo included—are anticipating key data readouts before the end of 2024. BioSpace takes a closer look at five of these.

Novo Nordisk’s CagriSema

Phase III

Novo Nordisk reeled in $1.7 billion from Wegovy in the second quarter of 2024, but the GLP-1 powerhouse isn’t resting on this success. Instead, Novo has a pipeline full of obesity candidates, including CagriSema, for which Phase III results are expected in the second half of 2024, according to Mizuho.

CagriSema combines Wegovy with cagrilintide, a long-acting amylin analog that promotes weight loss by delaying gastric emptying and lowering blood glucose levels. Suvannevejh noted that combination approaches could lead to “hopefully even greater weight loss.”

In August 2022, Novo posted results from a Phase II study in overweight individuals with type 2 diabetes, showing that CagriSema could elicit a 15.6% body weight reduction over 32 weeks, compared to a 5.1% reduction with Wegovy alone and an 8.1% reduction with cagrilintide alone.

CagriSema is also going up against Lilly’s Zepbound in a head-to-head Phase III trial that kicked off in November 2023. The trial, which is targeting enrollment of 800 people, is slated to be completed in August 2025, according to Clinicaltrials.gov.

Amgen’s MariTide

Phase II

During a first-quarter 2024 earnings report in May, Amgen CSO James Bradner expressed confidence in the company’s next-generation obesity candidate MariTide. At the time, Amgen claimed positive Phase II results for MariTide but did not reveal details. Investors and other obesity space watchers could get a clearer picture later this year when Amgen is expected to provide an interim Phase II analysis.

MariTide is an injectable bispecific molecule that can simultaneously inhibit the GIP receptor and activate the GLP-1 receptor. Phase I data for the candidate, published in February, showed that MariTide could reduce body weight by 14.5% after 85 days in obese participants without diabetes. These data also suggest the investigational treatment could have longer-lasting effects than currently available GLP-1 treatments, according to Amgen.

Suvannevejh called MariTide “a very high-profile program” for Amgen investors, noting that a lot of the more recent movement in the company’s stock is owing to its possession of an obesity drug.

Novo Nordisk’s Monlunabant

Phase II

In August 2023, Novo Nordisk put up more than $1 billion to acquire Inversago Pharma and its lead asset, INV-202, now known as monlunabant. Novo will have an opportunity to gauge the value of this buy in the second half of 2024, when Phase II data from the candidate are expected.

Monlunabant is an oral blocker of the cannabinoid receptor 1 (CB1 receptor), which is important for the regulation of metabolism and appetite. According to Novo’s acquisition announcement, CB1 is commonly found on peripheral tissues—including the kidneys and liver—and blocking this receptor has been shown in preclinical studies to have therapeutic effects across a wide range of cardiometabolic and fibrotic diseases.

Suvannevejh said the upcoming data are “relatively highly anticipated” and that the results could also have an impact on the fortunes of two other companies targeting the CB1 receptor, Corbus Pharmaceuticals and Skye Bioscience.

He noted that there have been concerns in the past regarding the safety profile of this drug class, specifically the risk of suicidality. However, Suvannevejh said, “the fact that Novo plunked down over a billion dollars would seem to suggest that perhaps either this suicidality never really was an issue to begin with . . . or this next generation of drugs have kind of figured it out and kind of engineered around the suicidality.”

Aphaia Pharma’s APHD-012

Phase II

Multinational biopharma company Aphaia Pharma is developing APHD-012, a proprietary oral glucose formulation designed to restore endogenous nutrient-sensing pathways in the gastrointestinal tract.

APHD-012 is intended to “reactivate the intestinal nutrient-sensing cells, which are underutilized as part of the complex obesity-associated pathology,” explained Steffen-Sebastian Bolz, chief scientific officer at Aphaia. “APHD-012 creates a broad metabolic impact by restoring the release of the entire spectrum of nutrient-induced hormones,” he told BioSpace in an email.

Aphaia is anticipating a wealth of topline data from a Phase II trial of APHD-012, with results from Arm 1 of the study expected in Q3 and Arm 2 in Q4. In June, the company announced it had completed enrollment in the second arm of the trial.

Bolz said the Phase I and II trials have shown “very benign adverse effect profiles” that could encourage the long-term use of the drug to “permanently restore metabolic balance and [elicit] effective chronic weight management.”

Terns Pharmaceuticals’ TERN-601

Phase I

In the oral GLP-1 bucket, California-based biotech Terns Pharmaceuticals is expecting topline Phase I data for its lead obesity candidate, TERN-601, in the second half of this year. In a November 2023 press release announcing the dosing of the first participant in the Phase I trial, Terns noted that this readout would provide “proof of concept” data for the candidate, an oral GLP-1 receptor agonist.

While in the early stage, Suvannevejh said that in the obesity space most investors have looked at Phase I data as a proxy for the overall quality of the drug. First, he said, this is because a safety and tolerability readout is especially important for a GLP-1 class in which there have been noted tolerability issues. “But perhaps more importantly, you do get an initial, albeit just 28-day, read of the efficacy.”

https://www.biospace.com/drug-development/5-obesity-readouts-to-watch-in-the-second-half-of-2024

FDA Action Alert: Ascendis, Gilead and Regeneron

 

In the next two weeks, the FDA will hand down its verdicts for three drug applications, including ones for multiple myeloma and hypoparathyroidism therapies.

The remainder of August looks sparse for the FDA, with just three target action dates over the next two weeks, including one for a bispecific antibody for multiple myeloma and another for an oral drug for an autoimmune liver disease.

Read below for more.

Ascendis Awaits Delayed Decision on TransCon PTH

Following a three-month extension in May 2024, the FDA is now approaching its August 14 deadline to render a verdict on Ascendis Pharma’s TransCon PTH (palopegteriparatide), which the Danish company is proposing for adults with hypoparathyroidism.

Patients with hypoparathyroidism suffer from impaired function of their parathyroid glands, which often manifests as headaches, muscle cramps and weakness. Once it progresses, hypoparathyroidism can result in long-term complications such as calcium deposits in the kidneys and brain. There are currently no dedicated therapies for the disease; patients are managed using high-dose calcium and active vitamin D therapy.

Designed to be administered via a once-daily subcutaneous injection, TransCon PTH is a long-acting prodrug of the parathyroid hormone. According to Ascendis’ website, it works by helping the body restore physiologic levels of the parathyroid hormone for 24 hours each day, in turn addressing the short- and long-term symptoms of hypoparathyroidism.

The FDA previously rejected TransCon PTH in May 2023 due to manufacturing concerns—though it flagged no problems with the drug’s safety and efficacy. Ascendis filed its resubmission in late 2023 with a decision originally set for May 14. However, following an additional data submission, the FDA pushed its decision date back by three months.

Gilead Gears Up for Potential Approval of Seladelpar in Primary Biliary Cholangitis

Gilead Sciences is developing the selective peroxisome proliferator-activated receptor delta (PPARδ) agonist seladelpar to treat the autoimmune liver disease primary biliary cholangitis (PBC). The FDA is expected to release its decision on or before August 14.

Designed to be taken orally, seladelpar is a potential first-in-class drug that works by blocking the PPARδ protein, which is a transcription factor central to several physiological processes, such as lipid metabolism and inflammation. Seladelpar’s mechanism of action could help regulate the immune response, in turn addressing a key underlying mechanism of PBC.

Seladelpar was originally developed by CymaBay, which in December 2023 filed an NDA for the drug candidate, backed by findings from the Phase III RESPONSE and ENHANCE studies, which together enrolled more than 500 PBC patients, as well as the long-term open-label ASSURE trial and Phase II data.

A few months later, in February 2024, Gilead snapped up CymaBay in a $4.3 billion acquisition agreement that gave it ownership over seladelpar.

In May 2024, amid the FDA’s ongoing review of seladelpar, Gilead published interim late-stage data from ASSURE, touting a significant reduction in pruritus in patients treated with the oral PPARδ blocker. Additionally, 37% of patients saw normalized levels of the alkaline phosphatase enzyme, a key liver biomarker.

Regeneron Anticipates FDA Verdict for Multiple Myeloma Candidate

By August 22, the FDA is expected to release its decision on Regeneron Pharmaceuticals’ investigational bispecific antibody linvoseltamab, which is proposed for the treatment of relapsed or refractory multiple myeloma.

Linvoseltamab works by targeting both the B-cell maturation antigen and CD3 protein, which is found on T cells. Through this mechanism of action, the bispecific antibody brings malignant B cells closer to T cells and promotes the body’s cancer-killing response. In December 2023, Regeneron released early data from the Phase I/II LINKER-MM1 study, showing that almost half of treated patients achieved complete response or better after a median follow-up of 11 months. Objective response rate was 71%.

However, the study also revealed several safety concerns with linvoseltamab. Adverse events Grade 3 or worse arose in 85% of patients, with the most common side effect being cytokine release syndrome. Fourteen participants, corresponding to 12% of the study sample, died due to treatment-emergent toxicities.

Regeneron released updated data from LINKER-MM1 in June 2024 affirming the high response rate associated with linvoseltamab, alongside promising progression-free and overall survival data.

Regeneron is also seeking European approval for linvoseltamab. The European Medicines Agency accepted its Marketing Authorization Application in February 2024.

https://www.biospace.com/fda/fda-action-alert-ascendis-gilead-and-regeneron

Vegan diet cuts inflammation better than Mediterranean

 Eating a low-fat vegan diet reduces harmful inflammatory dietary compounds called advanced glycation end-products (AGEs) by 73%, compared to no reduction on a Mediterranean diet, according to new research by the Physicians Committee for Responsible Medicine published in Frontiers in Nutrition. The decrease in AGEs on the vegan diet was associated with an average weight loss of 13 pounds, compared with no change on the Mediterranean diet.

The reduction of dietary AGEs on the low-fat vegan diet came mainly from excluding the consumption of meat (41%), minimizing the consumption of added fats (27%), and avoiding dairy products (14%).

"The study helps bust the myth that a Mediterranean diet is best for weight loss," says lead study author Hana Kahleova, MD, Ph.D., director of clinical research at the Physicians Committee for Responsible Medicine.

"Choosing a low-fat vegan diet that avoids the dairy and oil so common in the Mediterranean diet helps reduce intake of harmful advanced glycation end-products leading to significant weight loss."

AGEs may be ingested through the diet, and animal products are generally higher in AGEs than plant foods. Cooking with high heat under dry conditions, such as grilling, leads to significant formation of AGEs, especially in animal-derived foods, which are also rich in fats. High amounts of AGEs circulating in the body can contribute to insulin resistance, which can lead to weight gain. AGEs are also linked to inflammation and oxidative stress, which contribute to chronic diseases like heart disease and type 2 diabetes.

The new research is a secondary analysis of a previous Physicians Committee study comparing a low-fat vegan diet to a Mediterranean diet. The study randomly assigned participants to either a low-fat vegan diet, which consisted of fruits, vegetables, grains, and beans, or a Mediterranean diet, which focused on fruits, vegetables, legumes, fish, low-fat dairy, and extra virgin olive oil, for 16 weeks. Neither group had a calorie limit.

Participants then went back to their baseline diets for a four-week washout period before switching to the opposite group for an additional 16 weeks. Dietary AGEs were calculated based on self-reported dietary intake records. AGE scores were assigned to each food item, using a published database of AGE content.

"Our research shows that you can use the power of your plate to lose weight with a low-fat vegan diet that's rich in fruits, vegetables, grains, and beans and low in AGEs," adds Dr. Kahleova. "It's a simple and delicious way to maintain a healthy weight and fight chronic disease."

More information: Hana Kahleova et al, Dietary advanced glycation end-products and their associations with body weight on a Mediterranean diet and low-fat vegan diet: a randomized, cross-over trial, Frontiers in Nutrition (2024). DOI: 10.3389/fnut.2024.1426642

https://medicalxpress.com/news/2024-08-vegan-diet-mediterranean.html

Serotonin changes how people learn and respond to negative information

 Increasing serotonin can change how people learn from negative information, as well as improving how they respond to it, according to a new study published in the journal Nature Communications.

The study by scientists at the University of Oxford's Department of Psychiatry and the National Institute of Health and Care Research (NIHR) Oxford Health Biomedical Research Center (OH BRC) found people with increased serotonin levels had reduced sensitivity to punishing outcomes (for example, losing money in a game) without significantly affecting sensitivity to rewarding ones (winning money).

The study involved 26 participants who were given the drug to increase serotonin, with a further 27 in a control group, who were asked to do a series of tasks measuring learning and behavioral control. State-of-the-art models were then used to understand participant behavior.

The researchers found that increasing serotonin made individuals better able to control their behavior, particularly when exposed to negative information. The study also showed that elevated serotonin levels benefited different types of memory.

Michael Colwell of Oxford's Department of Psychiatry, the lead author of the paper, said, "These findings shed new light on how serotonin shapes human behavior, particularly in negative environments.

"We believe it may offer important insights into the cause and treatment of depression."

Instead of using traditional antidepressants (SSRIs or selective serotonin reuptake inhibitors) to test responses, the researchers used a new technique to test the effects of serotonin, using a selective serotonin releasing agent, a drug currently used to treat a rare form of epilepsy called Dravet Syndrome. Unlike traditional techniques, this novel drug directly increases serotonin levels in the human brain.

Professor Catherine Harmer, Professor of Cognitive Neuroscience at the University of Oxford, and OH BRC Theme Lead for Depression Therapeutics said, "Despite nearly a century of research, our understanding of how serotonin influences human behavior has remained unclear and controversial.

"This provides us with some exciting new information about the role of serotonin in humans. It shows that serotonin, which has been implicated in depression and in the effects of antidepressants, has more of a role in processing negative things, rather than boosting positive responses.

"Serotonin is often referred to colloquially as the 'happy chemical' but perhaps it is time we thought of it as the 'not-so-bad chemical.'"

Professor Susannah Murphy, Associate Professor at the University of Oxford, said, "By directly manipulating levels of serotonin in the brain, this study helps us to understand some of the core functions this important brain chemical plays in humans.

"Our findings underscore the central role that serotonin plays in effortful cognitive processes, such as our ability to put the brakes on unwanted behaviors. This study helps to further understand why drugs that change serotonin levels are effective treatments for many mental illnesses, including depression, anxiety and obsessive-compulsive disorder."

More information: Michael J. Colwell et al, Direct serotonin release in humans shapes aversive learning and inhibition, Nature Communications (2024). DOI: 10.1038/s41467-024-50394-x

https://medicalxpress.com/news/2024-08-serotonin-people-negative.html

'Keto diet study shows higher LDL cholesterol, apolipoprotein B, reduced gut bacteria'

 A team of health and nutrition specialists at the University of Bath, working with colleagues from the University of Bristol, the Oxford University Hospital Trusts, Maastricht University, and the Teagasc Food Research Center, has found that people on a ketogenic diet may experience an increase in LDL cholesterol levels, higher apolipoprotein B levels and reductions in certain gut bacteria.

In their study, published on the open-access site Cell Reports Medicine, volunteers went on a ketogenic diet for a month so the researchers could study its impact on their bodies.

A ketogenic diet consists of a drastic reduction in consumption of carbohydrates, replacing them with fats from meat, dairy, cheese, eggs and other foods such as avocados. Prior research has shown that those adhering to the rules do lose weight, but also that the diet may cause other health problems such as nutrition deficiencies, digestive problems, kidney stones and, over the long term, bone problems.

In this new effort, the research team suspected that the diet may also lead to increases in LDL cholesterol levels and possibly other problems. To find out if that might be the case, they conducted a randomized controlled trial by recruiting volunteers to go on the diet for a month and then to undergo a medical evaluation to determine changes.

The trial involved 53 non-obese adults. A third of them went on a ketogenic diet, another third went on a low-sugar diet and the remaining third ate what the researchers describe as a moderate diet to serve as a control.

After one month, all the volunteers were tested. The research team found that those volunteers on the ketogenic diet had lost on average 1.6 kg of fat. They also had 16% higher levels of LDL cholesterol in their blood than the control group and 26% higher levels of apolipoprotein B, a protein known to clog arteries. Those on the low-sugar diet lost on average of 1 kg of fat and had 10% lower levels of LDL cholesterol in their blood samples and no change in apolipoprotein B levels.

The researchers noted that those volunteers who had been on the ketogenic diet also had reduced levels of a type of gut bacteria known to be involved in promoting a strong immune system and also in the production of vitamin B.

More information: Aaron Hengist et al, Ketogenic diet but not free-sugar restriction alters glucose tolerance, lipid metabolism, peripheral tissue phenotype, and gut microbiome: RCT, Cell Reports Medicine (2024). DOI: 10.1016/j.xcrm.2024.101667

https://medicalxpress.com/news/2024-08-keto-diet-ldl-cholesterol-higher.html

Russian Military Ship Spotted 30 Miles Off Alaska By Coast Guard

A U.S. Coast Guard cutter on routine patrol around Alaska’s Aleutian Islands came across a Russian military ship in international waters but within the U.S. exclusive economic zone, the AP reported citing US military officials.

The crew on the U.S. Coast Guard Cutter Alex Haley on Monday detected the vessel about 30 miles (48 kilometers) southeast of the Amukta Pass, the Coast Guard said in a Friday statement. A helicopter aircrew from Coast Guard Air Station Kodiak also spotted the vessel.

The vessel was “transiting in international waters but still inside the U.S. Exclusive Economic Zone,” which extends 200 nautical miles (370 kilometers) from the U.S. shoreline, according to the statement.

The Coast Guard vessel did not communicate with the Russian ship but followed it as it moved east, the statement said.

“We met presence with presence to ensure there were no disruptions to U.S. interests in the maritime environment around Alaska” Cmdr. Steven Baldovsky, commanding officer of the Alex Haley, said in the statement.

In July, the Coast Guard while on patrol spotted four Chinese military ships north of the Amchitka Pass in the Aleutian Islands in international waters but also within the U.S. exclusive economic zone, officials said.

Russian and Chinese bombers later that month flew together for the first time in international airspace off the coast of Alaska, in a new show of expanding military cooperation that U.S. Defense Secretary Lloyd Austin said at the time raises concerns.

The flights weren’t seen as a threat, and the bombers were tracked and intercepted by U.S. and Canadian fighter jets. But it was the first time that Chinese bomber aircraft flew within the Alaskan Air Defense Identification Zone. And it was the first time Chinese and Russian aircraft took off from the same base in northeast Russia.

https://www.zerohedge.com/markets/russian-military-ship-spotted-30-miles-alaska-coast-guard