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Wednesday, July 10, 2024

'Bird flu response in Michigan sparks COVID-era worry on farms'

 Some dairy farmers are resisting Michigan's nation-leading efforts to stop the spread of bird flu for fear their incomes will suffer from added costs and hurt rural America.

The government's restrictions, which include tracking who comes and goes from farms, are rekindling unwanted memories of COVID-19 in Martin and other small towns in central Michigan.

The state has two of the four known cases in humans, all dairy workers, since federal authorities confirmed the world's first case in U.S. cattle in late March. The state has tested more people than any of the 12 states with confirmed cases in cows, according to a Reuters survey of state health departments. Testing policies vary by state.

Public health experts fear the disease has the potential to turn into another pandemic just a few years after COVID-19. As those worries mount, the acceptance and success or failure of Michigan's proactive response is being watched by other states looking for a roadmap that goes beyond federal containment recommendations.

More than a dozen interviews with Michigan producers, state health officials, researchers and industry groups, along with preliminary data, so far show limited dairy farmer participation in efforts to stem and study the virus. In some cases, calls from local health officials go unanswered, money for dairy farm research is left unclaimed, and workers still milk cows without extra protective gear.

Brian DeMann, a dairy farmer from Martin, Michigan, said the outbreak and state's response recalls COVID-19. The 37-year-old believes Michigan's rules to contain bird flu would be more widely accepted if they came as recommendations rather than requirements for farmers.

"Nobody knows if these things that we're being told to do are going to stop it," said DeMann, who echoed an uncertain view shared by other farmers. "Just like 2020, people didn't like to be told what to do."

This spring many U.S. dairy owners did not heed federal recommendations to offer more protective equipment to employees, according to farmers and workers. DeMann said he did not invest in new protective gear, such as masks, for his workers because it is unclear how the virus is spreading.

NO EXTRA GEAR

About 900 permitted dairy farms dot Michigan's countryside, with cows in open-air barns and piles of feed covered with protective tarps and old tires used as weights.

Tim Boring, Michigan's agriculture director, said social stigma and economic concerns around infections have discouraged farmers from testing cows for bird flu in the nation's sixth biggest milk producer.

"There's a lot of factors that go into the concerns about farms coming forward with positive operations," he said. "We know this has been a challenge in Michigan."

The state last reported an infected dairy herd on July 9, its 26th to test positive. Five other states have also confirmed cases in the past month, and about 140 herds have been infected nationally since March, according to U.S. Department of Agriculture data.

Michigan is offering farms up to $28,000 to entice those with infected herds to participate in research. More than a dozen farms have so far expressed interest, the state said.

Separately, the federal government is offering financial assistance. Twelve of 21 herds enrolled in financial support from USDA are from Michigan, according to the agency.

To boost testing, USDA launched a voluntary program in which U.S. farmers can test tanks of milk weekly for bird flu. Six farmers in six states have enrolled one herd each, but a Michigan farmer is not among them yet.

"I really would like to see that in every single herd," said Zelmar Rodriguez, a Michigan State University dairy veterinarian studying infections.

'NEW THREAT'

Michigan's agriculture department said it has up to 200 people responding to bird flu cases in poultry and cattle, including coordinating with USDA on outbreak investigations. Veterinarians in other states said they tracked Michigan's cases to assess the risks for transmission.

"Michigan is doing a good job with their diagnostics and trying to identify where the disease is," said Mike Martin, North Carolina's state veterinarian.

Michigan's outbreak in cows began after an infected Texas farm shipped cattle to Michigan in March before the virus was detected, according to USDA. Weeks later, a Michigan poultry farm also reported symptoms and tested positive. Whole genome sequencing suggested the virus spilled over from the dairy farm to the poultry flock.

USDA now thinks the virus has spread indirectly through people and vehicles moving on and off infected farms.

Chickens owned by Michigan's largest egg producer, Herbruck's Poultry Ranch, were infected because the virus spread from cattle, said Nancy Barr, executive director of Michigan Allied Poultry Industries, an industry group. Reuters is first to report the link to Herbruck's from dairy cow transmission.

"It's a new threat to us," Barr said.

Herbruck's told the state in May it was laying off about 400 workers after bird flu decimated flocks in Ionia County. The company said in a public notice it planned to rehire employees as it rebuilds its flocks, a process that can take six months.

As of late June, Ionia County poultry farmers received $73.2 million in indemnity payments from the U.S. government for bird-flu losses, the most of any county in the country that had to cull infected flocks since February 2022, according to data Reuters obtained from the USDA.

MAIN STREET

The layoffs struck fear in Ionia, a city of about 13,000 people in central Michigan with a brick-paved Main Street and mural of the Mona Lisa. Business owners said unemployed workers have less money to spend at time when local stores already struggle to compete with Walmart and Meijer.

"I just thought, 'Oh great, here goes the store,'" said Jennifer Loudenbeck, owner of the Downtown Vintage Resale shop.

Alex Hanulcik, who owns a fresh fruit stand, said he knows a Herbruck's employee who left town to find work in the southern U.S. after being terminated.

"I really feel for the employees," Hanulcik said. "They were blindsided."

Herbruck's declined to comment.

Dairy farmers said they are constantly worrying their cows may be the next to become infected, yet they are unsure exactly how to protect them.

Doug Chapin, a dairy farmer in Remus, Michigan, said he held meetings with employees to inform them of the risks of the virus. He is trying to make workers wear protective eye gear, though they objected in the past because glasses must be cleaned if milk sprays on them.

"You're thinking about it all the time," he said about the virus.

Michigan has plans to test dairy workers for signs of prior infections with first-in-the-nation blood testing.

The state has already monitored thousands of people for bird flu symptoms using a complex contact tracing system that texts them three times daily, said Chad Shaw, health officer for the Ionia County Health Department.

Some farmers remain reluctant to engage with local health authorities, though.

The Branch-Hillsdale-St. Joseph Community Health Agency began reaching out to farms generally to offer medical care for seasonal workers because of bird flu cases, said health officer Rebecca Burns. There has been little interest, she said.

"These guys aren't used to us calling them," Burns said.

HARD HIT

Michigan has detected the third most infected dairy herds of any state, after Idaho and Colorado, and lost 6.5 million chickens in April alone from outbreaks on poultry farms, USDA data show.

The Biden administration in late April began requiring lactating cows to test negative before being shipped over state lines.

Michigan went further and in May started requiring farms to keep logs of visitors, disinfect delivery trucks that could carry the virus, and take other safety steps. The state this month began requiring negative tests for non-lactating cows to be shown at fairs.

Colorado reported the nation's fourth human case on July 3. The U.S. government awarded $176 million to Moderna to advance development of its bird flu vaccine for humans.

Two dozen companies are working on a vaccine for cattle, U.S Agriculture Secretary Tom Vilsack said, as about 140 herds nationally have tested positive.

"Michigan's been the forefront on providing information, providing access to information that really is helpful," Vilsack told Reuters.

https://www.yahoo.com/news/bird-flu-response-michigan-sparks-100706733.html

Moleculin Completes End of Phase 2 Meeting with FDA for Annamycin in AML

 Moleculin Biotech, Inc, (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, today announced the completion of its End of Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA) for its Phase 1B/2 clinical trial evaluating Annamycin in combination with Cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as AnnAraC) for the treatment of subjects with AML as both first line therapy and for subjects who are refractory to or relapsed after induction therapy (MB-106). The Company expects to report outcomes from the EOP2 meeting upon receipt of official minutes from FDA which is expected by the end of Q3 2024.

https://www.biospace.com/article/releases/moleculin-completes-end-of-phase-2-meeting-with-fda-for-annamycin-in-aml/

Amgen Axes Development of Early-Stage Bispecific T-Cell Engager for Solid Tumors

 Amgen on Monday terminated the development of its investigational bispecific T-cell engager AMG 794, which it had been studying in a Phase I trial for several solid tumors including non-small cell lung cancer and epithelial ovarian cancer.

In an update to the clinicaltrials.gov website, the company noted that it “made the business decision to discontinue development of AMG 794” while maintaining that “the safety profile of AMG 794 remains unchanged.” It is not clear what exactly led to the termination of the AMG 794 program.

In line with the discontinuation of AMG 794, Amgen will also stop the Phase I study which was assessing the safety and tolerability of the bispecific T cell engager in several malignant solid tumor indications.

AMG 794 was designed to target claudin-6, a tight junction protein crucial to the connectivity, permeability and adhesion between cells. In cancer, claudin-6 is abnormally expressed compromising the tight junction and loosening cell layers—a key hallmark of cancer progression and metastasis. Claudin-6 is typically highly expressed in malignant cells but is rare in healthy tissues.

The bispecific T-cell engager is still listed on Amgen’s pipeline, which indicates that the molecule uses its proprietary BiTE technology that leverages the body’s immune functions to treat cancer. AMG 794 was also designed to have an extended half-life, prolonging its presence in patients’ bodies.

According to the pharma’s website, these bispecific engagers consist of two targeting regions of two antibodies. This structure allows these molecules to create a bridge cytotoxic T cells and tumor cells, facilitating the immune system’s anti-cancer activity.

In May 2024, Amgen’s BiTE platform resulted in an accelerated approval for the bispecific molecule tarlatamab, which is now being marketed under the brand name Imdelltra for extensive-stage small cell lung cancer. Imdelltra can be used in patients with disease progression on or after platinum chemotherapy. Amgen will need to validate Imdelltra’s clinical benefit in a confirmatory trial to maintain its approval.

Several other companies are also leveraging bispecific T-cell engagers for cancer. Roche owns Columvi (glofitamab) which targets CD3 on T cells and CD20 on cancerous B cells. In June 2023, the FDA granted Columvi accelerated approval for relapsed or refractory diffuse large B-cell lymphoma.

Gilead Sciences is pushing the technology even further with its investigational trispecific antibodies. In March 2024, the company partnered with Netherlands-based Merus to advance this approach, which can bind three targets simultaneously and potentially lead to a more robust immune response against cancer.

"We have seen the successful application of bispecific antibodies as an immune-modulating modality used to treat cancer,” Flavius Martin, executive vice president of research at Gilead, said in a statement at the time. “We are now looking ahead to the development of additional multispecific antibodies capable of driving robust anti-tumor immune responses with an improved efficacy and safety profile."

https://www.biospace.com/article/amgen-axes-development-of-early-stage-bispecific-t-cell-engager-for-solid-tumors/

'Biden' Tells Voters To "Google Project 2025"; Voters Have Their Own Search Suggestions

 by Steve Watson via Modernity.news,

Joe Biden’s cringe team sent out this post on his X account Tuesday:

It was meant to be a scary warning about Trump literally being Hitler… or something, but because this is Biden’s “team”, it spectacularly backfired.


New software update is ready:

How about have him do something for us first?

Everyone knows it’s not actually Biden tweeting.

Someone followed the order and here’s what popped up:

If you do actually Google it, you find out quickly that it’s just a shitty leftist paranoid fantasy.

If you’re confused...

There are a few more pressing things to search for first:

Here are the rest of Biden’s keystrokes:

*  *  *

https://www.zerohedge.com/political/biden-tells-voters-google-project-2025-voters-have-their-own-search-suggestions

Alnylam Could Challenge Pfizer in ATTR-CM But Some Want Full Data

 Unveiled late last month, topline results from a Phase III trial of Alnylam’s RNAi therapy Amvuttra in ATTR amyloidosis with cardiomyopathy are turning some heads. The treatment showed a statistically significant reduction in all-cause mortality and recurrent cardiovascular events.

“I expected this readout to be positive, but this was extremely positive,” said Kostas Biliouris, director and equity research analyst at Bank of Montreal Capital Markets. “I think the results reflect the best-case scenario.”

The initial results appear promising, but a clearer picture will emerge when the full data come out later this summer. Further details of the HELIOS-B study will be presented as an abstract at the European Society of Cardiology’s congress in London, taking place Aug. 30 to Sept. 2.

Paul Matteis, head of the therapeutics research team at Stifel, told BioSpace that not having those details is one of the biggest open questions at the moment. Amvuttra will have to face competition from Pfizer, whose ATTR-CM oral drugs Vyndamax and Vyndaqel were approved in 2019. The Vyndaqel family of drugs has earned blockbuster status, bringing in $1.1 billion in sales in the first quarter of 2024, a 66% boost from Q1 2023.  

Research Outlook and the ATTR-CM Space

In the HELIOS-B trial, Amvuttra reduced the risk of mortality and recurrent cardiovascular events by 28% in patients also taking Pfizer’s Vyndamax compared to a placebo. Those only taking Amvuttra saw the risk drop by 33%. The risk of death from all causes, one of the secondary endpoints, was lowered by 36% in patients also taking Vyndamax, while it was reduced by 35% in those on Amvuttra monotherapy. Patients on Amvuttra also showed statistically significant improvements in other metrics, such as the six-minute walk test.

“Given the data we have right now, the totality of the data and the limited information . . . I believe this is potentially the best profile in ATTR cardiomyopathy,” Biliouris told BioSpace.

Matteis said Amvuttra is at least “tied at the top” based on the topline data but noted that the most significant caveat in comparing Amvuttra to Vyndamax or BridgeBio’s investigational drug acoramidis is that the duration of Alnylam’s study is longer, and the interest will be in what the data at 30 months look like. However, he noted it is unlikely that the 30-month data will suggest Amvuttra is worse than its competition.

“[Alnylam is] probably tied for first, in terms of the overall product offering and how compelling it is under the impetus to prescribe it,” he said.

Some experts have reservations about whether Amvuttra can challenge Pfizer, however. Myles Minter, a research analyst at William Blair, told BioSpace that Alnylam has “more work to do” as it is going up against Vyndamax, a safe drug with an “impressive” hazard ratio that has benefits in cardiovascular outcomes. He also claims that the “knock” on Amvuttra is that the clinical trials were done in patients who had much more severe cardiovascular events, which differs from when the drug would actually be prescribed.

“That’s not how the diagnosis is done today. So, we don’t have control data, like proper industry-standard control data against placebo in the patient population that we’re currently treating, which is early on in the treatment course,” Minter said.  

He noted that the detailed data expected at the European Society of Cardiology’s congress later this summer will also help determine whether Amvuttra is competitive against the industry standard.

Amvuttra’s Financial Outlook

Minter said that right now, Amvuttra, which is only approved in polyneuropathy, is generating over $900 million in sales and growing 18% year over year from a patient population of between 30,000 and 60,000. The cardiomyopathy opportunity may allow Amvuttra’s population to expand 10-fold as more noninvasive diagnosis techniques are available for ATTR-CM, he said.

Minter estimates that the combined polyneuropathy and ATTR-CM peak sales of Amvuttra would be $3.7 billion in the U.S. and $1.8 billion in the European Union. Matteis projected peak drug sales of around $5 billion to $6 billion, but noted that the competition with Vyndamax will remain and said Pfizer’s drug will maintain its blockbuster status.

Another element of the financial equation is pricing. Amvuttra is currently priced much higher than Vyndamax, but Matteis said there is a “general expectation” that it will be lowered to some degree. He also added that there may be other “economic drivers” to Amvuttra, as a practice could make more money prescribing the drug because it is an in-office injection.

“There’s a chance where [Alnylam is] in pole position,” Matteis said. “But it is a little bit premature to draw that conclusion without seeing the full data.”

https://www.biospace.com/article/alnylam-could-challenge-pfizer-in-attr-cm-but-experts-want-full-data/

Amylyx Pivots to GLP-1 Space, Acquires Phase III-Ready Asset from Eiger

 Amylyx Pharmaceuticals announced Wednesday it has acquired a glucagon-like peptide-1 receptor antagonist, avexitide, from Eiger BioPharmaceuticals that is ready for Phase III trials and has been granted FDA Breakthrough Therapy Designation for post-bariatric hypoglycemia and congenital hyperinsulinism.

The novel, first-in-class GLP-1 was picked up for $35 million from Eiger, which entered Chapter 11 proceedings in April 2024 with plans to sell all its assets. According to Amylyx, avexitide has already been investigated in five clinical trials for post-bariatric hypoglycemia (PBH), a common complication of bariatric surgery, and has also been studied in congenital hyperinsulinism (HI). Avexitide has also been granted an FDA Orphan Drug Designation in hyperinsulinemic hypoglycemia and a Rare Pediatric Disease Designation in congenital HI.

The company is placing avexitide into its pipeline and is planning to start Phase III studies in PBH in the first quarter 2025. The company is also starting conversations with the HI community to start a Phase II study at the Children’s Hospital of Philadelphia. Josh Cohen, co-CEO of Amylyx, said the company plans to get the Phase III data by 2026 and to go to market by 2027.

So far, Phase II and Phase IIb studies of avexitide in PBH have shown a statistically significant reduction in hypoglycemic events characterized by low blood glucose.

Justin Klee, co-CEO of Amylyx, told BioSpace that the company is searching for assets with a clear mechanism of action for targeting diseases..

“We want to have compelling preclinical and clinical data, and many ways, most importantly, an opportunity to make a real impact and help people with high-end medical needs,” Klee said. “And in many ways, this was the first asset that really checked all the boxes.”

Klee noted that GLP-1 agonists are helpful in conditions characterized by too much glucose and insufficient insulin. Still, some diseases have too much insulin and not enough glucose, which is what avexitide is meant to counter.

Amylyx’s targeting of the GLP-1 space follows the company’s decision to pull its ALS drug Relyvrio off the shelves earlier this year and to axe around 70% of its workforce under a restructuring plan. The ALS drug failed its Phase III PHOENIX trial and could not improve scores on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale at 48 weeks versus placebo, while falling short of its secondary endpoints.

The company has been focused on its lead asset, AMX0035, for adults with Wolfram syndrome. In April 2024, a Phase II study showed that the candidate improved pancreatic function and glycemic control.

https://www.biospace.com/article/amylyx-pivots-to-glp-1s-acquires-phase-iii-ready-asset-from-eiger/