AbbVie Expands Immuno Portfolio With $250M Celsius Buy as Humira Hits Patent Cliff

 AbbVie on Thursday announced that it has bought Cambridge, Massachusetts-based startup Celsius Therapeutics and its lead inflammatory bowel disease antibody CEL383.

Details of the acquisition agreement were sparse, with the companies only revealing that AbbVie will snap up all of Celsius’ remaining equity for $250 million in cash, subject to certain adjustments. The companies have not yet announced when they plan to close the transaction.

“We are eager the advance the development of CEL383 with a goal of helping more patients with [inflammatory bowel disease (IBD)] achieve remission,” Kori Wallace, global head of immunology clinical development at AbbVie, said in a statement.

Developed using Celsius’ proprietary SCOPE platform, which allows the startup to “understand the cells that drive disease progression,” CEL383 is a potentially first-in-class monoclonal antibody that works by targeting the TREM1 protein. TREM1 mediates the interaction between the microbiome and the immune system while amplifying mucosal inflammation, according to the biotech’s website.

Preclinical studies have validated this mechanism of action, showing that CEL383 could disrupt TREM1 signaling and lowering the concentration of several inflammatory mediators. CEL383 has recently completed a first-in-human, placebo-controlled, single-ascending-dose Phase I trial in healthy volunteers, designed to evaluate its safety, tolerability and pharmacokinetic profile.

Thursday’s acquisition of Celsius is part of AbbVie’s strategy to deepen its portfolio as it weathers a particularly steep patent cliff for its blockbuster immuno therapy Humira (adalimumab).

Since losing its most important patent protections, Humira has mostly retained market dominance despite the flurry of biosimilars that flooded the U.S. market. However, in April 2024, fueled by CVS Caremark delisting Humira from its major national commercial formularies, copycats have enjoyed a surge in demand and sales.

To shore up its revenues and target future growth, AbbVie has been striking a series of deals giving it access to promising assets and technologies. In February 2024,  the pharma put $713 million on the line for an exclusive right to develop, manufacture and commercialize OSE Immunotherapeutics’ investigational antibody OSE-230, being assessed for chronic and severe inflammation.

Soon after, AbbVie dropped $212 million to acquire Landos Biopharma gaining access to the oral NLRX1 agonist NX-13, which is being studied as a treatment for ulcerative colitis and Crohn’s disease. AbbVie has joined a recent biopharma spending spree in the projected $257 billion immunology market.

Outside the immuno space, AbbVie has also invested heavily in the mental health market entering a potential $2 billion deal with Gilgamesh Pharmaceuticals in May 2024 to develop neuroplastogens for psychiatric disorders.

https://www.biospace.com/article/abbvie-expands-immuno-portfolio-with-250m-celsius-buy-as-humira-hits-patent-cliff/

Illumina Reports $1.47B ‘Goodwill’ Impairment Charge After Grail Spinoff

 Sequencing giant Illumina on Thursday announced that it will take a $1.47 billion hit in the second quarter of 2024 related to the recently completed spinoff of cancer testing company Grail.

In an SEC filing, Illumina said the “goodwill impairment charge” corresponds to the “full remaining carrying value of goodwill” associated with Grail as of March 31, 2024. Illumina also expects to absorb a $420 million impairment charge for Grail’s in-process research and development intangible assets in the second quarter.

Illumina does not expect these goodwill impairments to translate into future material cash expenditures. The company will also not reflect these impairment charges from its non-GAAP figures.

Thursday’s impairment charges come days after the sequencing powerhouse successfully closed the spinoff of Grail—ending years of antitrust and regulatory trouble. Grail debuted on the Nasdaq Global Select Market on Tuesday with the ticker symbol GRAL.

The two companies parted on good terms—Illumina left grail with an undisclosed amount in funding to help the biotech achieve its long-term goals. The sequencing company also retains a minority 14.5% stake in the cancer detection company.

Illumina unveiled its plans to buy Grail in September 2020, putting up $8 billion in cash and stock to gain access to the biotech’s multi-cancer screening test Galleri. At the time, former Illumina CEO Francis deSouza considered Galleri as “among the most promising new tools in the fight against cancer.”

However, the acquisition soon attracted the attention of antitrust regulators in the U.S. and the European Union. In March 2021, the Federal Trade Commission issued a complaint letter against both companies, charging that their merger could compromise competition in the multi-cancer early detection market and “potentially increasing prices and reducing the choice and quality” of detection tests.

The European Commission (EC) launched an investigation into the deal in July 2021, which the companies did not wait to complete before consummating their merger. In response, the EC was forced to adopt binding measures in October 2021 to keep Illumina and Grail separate and independent from each other.

The EC eventually ruled that the companies had violated its merger regulations and levied a historic $476 million fine against Illumina.

Internally, the Grail acquisition has also been a source of discord for Illumina. In June 2023, deSouza stepped down as CEO amid activist Carl Icahn’s attacks and an attempt to seat three of his representatives on the company’s board. In December 2023, Icahn targeted what he called the “legacy conflicted directors” on Illumina’s board and campaigned for their removal.

https://www.biospace.com/article/illumina-reports-1-47b-goodwill-impairment-charge-after-grail-spinoff/

Chemo drug may cause significant hearing loss in longtime cancer survivors

 An interdisciplinary study led by researchers at the University of South Florida and Indiana University has uncovered significant findings on the long-term effects of one of the most common forms of chemotherapy on cancer survivors.

Published in JAMA Oncology, the study tracked a cohort of testicular cancer survivors who received cisplatin-based chemotherapy for an average of 14 years, revealing that 78% experience significant difficulties in everyday listening situations, negatively impacting their quality of life.

This collaborative research is the first to measure real-world listening challenges and hearing loss progression in cancer survivors over a long period of time.

"It's important that we understand the real-world effects of patients' sensory problems and if we can understand that, then we can develop better therapeutic strategies and preventive measures to improve the long-term quality of life for cancer survivors," said Robert Frisina, distinguished university professor and chair of the USF Department of Medical Engineering.

Cisplatin is commonly used in chemotherapy treatments for a variety of cancers, including bladder, lung, neck and testicular. It is administered intravenously and affects various parts of the body.

However, the ears are particularly vulnerable as they have little ability to filter out the drug, causing it to become trapped. This leads to inflammation and the destruction of sensory cells that are critical for coding sound, causing permanent hearing loss that can progressively get worse well after cisplatin treatments are completed.

Lead author Victoria Sanchez, associate professor in the USF Health Department of Otolaryngology Head & Neck Surgery, said that despite the known risks, there's a nationwide lack of routine hearing assessments for patients undergoing chemotherapy.

"Most patients still do not get their hearing tested prior to, during or after chemotherapy. Our study highlights the need for regular auditory evaluations to manage and mitigate long-term hearing damage."

The research team found higher doses of cisplatin led to more severe and progressing hearing loss, especially in patients with risk factors, such as high blood pressure and poor cardiovascular health. They also experienced increased difficulty hearing in common environments, such as a loud restaurant.

"It will be critically important to follow these patients for life. Their current median age is only 48 years, and eventually they will enter the years at which age-related hearing loss also begins to develop," said Dr. Lois B. Travis, Lawrence H. Einhorn Professor of Cancer Research at Indiana University School of Medicine and a researcher at the IU Melvin and Bren Simon Comprehensive Cancer Center.

This research is part of The Platinum Study, an ongoing research effort led by Dr. Travis to study cisplatin-treated testicular cancer survivors.

The hope is that this study will inspire further investigation into alternative chemotherapeutic protocols and preventive measures, such as FDA-approved drugs to prevent or reduce hearing loss.

"This research gives oncologists the information they need to explore alternative treatment plans that could reduce the long-term side effects, such as altering the dosages and timing of the cisplatin in the treatment, when that could be an appropriate option," Frisina said.

Innovative solutions, such as Pedmark, a new FDA-approved injection that mitigates cisplatin-induced hearing loss in children, represent promising steps forward, according to Frisina.

"We want to protect our hearing or treat a hearing loss if hearing damage occurs," Sanchez said. "Hearing allows us to connect to the world we love. Staying connected through conversations with family and friends, enjoyment of music and entertainment, staying safe and finding pleasure in our vibrant surroundings. Promoting optimal hearing for overall wellness is essential for healthy living."

According to the American Cancer Society, in addition to cisplatin, other platinum chemotherapy drugs, such as carboplatin, cause damage to the cochlea in the inner ear and lead to hearing loss. The risk of damage is greater with higher doses of chemotherapy.

More information: Victoria A. Sanchez et al, Comprehensive Audiologic Analyses After Cisplatin-Based Chemotherapy, JAMA Oncology (2024). DOI: 10.1001/jamaoncol.2024.1233

https://medicalxpress.com/news/2024-06-chemo-drug-significant-loss-longtime.html

Texas wins court block on Biden overtime pay rule

 A federal judge in Texas on Friday temporarily blocked a Biden administration rule from taking effect that would extend mandatory overtime pay to 4 million salaried U.S. workers.

U.S. District Judge Sean Jordan in Sherman, Texas, said the U.S. Department of Labor rule that is set to go into effect on Monday improperly bases eligibility for overtime pay on workers' wages rather than their job duties.

Jordan, an appointee of Republican former President Donald Trump, blocked the Labor Department from applying the rule to state workers in Texas pending the outcome of a legal challenge by the Republican-led state.

The Labor Department and the office of Republican Texas Attorney General Ken Paxton did not immediately respond to requests for comment.

The department can seek review of the ruling in the New Orleans-based 5th U.S. Circuit Court of Appeals, which is widely regarded as the most conservative federal appeals court.

The rule adopted in April would require employers to pay overtime premiums to salaried workers who earn less than $1,128 per week, or about $58,600 per year, when they work more than 40 hours in a week. The current threshold of about $35,500 was set in 2019.

Federal law exempts workers with "executive, administrative, and professional" (EAP) duties from receiving overtime pay, and the Labor Department has for decades used salary as one factor in deciding when that applies.

In adopting the rule, the department said that lower-paid salaried workers often do the same jobs as their hourly counterparts, but work more hours for no additional pay.

The rule also establishes automatic increases in the salary threshold every three years to reflect wage growth.

Texas in its lawsuit said the rule violates federal law by conditioning overtime exemptions primarily on workers' pay rather than their duties, and is seeking to strike it down nationwide.

Texas says that subjecting states to the overtime expansion violates their right under the U.S. Constitution to structure the pay of state employees and, in turn, decide how to allocate large portions of their budgets.

Jordan on Friday agreed that the Labor Department had overstepped its authority by effectively rewriting federal law.

"Since the ordinary meaning of the EAP Exemption focuses solely on duties, any rule implementing the EAP Exemption - including the 2024 Rule — must likewise center on duties," the judge wrote.

Jordan is also presiding over a challenge to the rule by business groups, and a small marketing firm is suing over the regulation in a different federal court in Texas.

https://finance.yahoo.com/news/texas-wins-court-block-biden-001350825.html

US military says it destroys seven Houthi drones, one ground control station

 The U.S. military said on Friday that it destroyed seven Houthi drones and one ground control station vehicle in Houthi-controlled Yemen.

https://www.marketscreener.com/news/latest/US-military-says-it-destroys-seven-Houthi-drones-one-ground-control-station-47270166/

Haiti PM travels to US as Kenyan police patrol capital

 Haitian Prime Minister Garry Conille left Port-au-Prince on Friday to travel to Washington and New York, as freshly deployed Kenyan police officers began patrolling the city as part of a U.N.-backed mission to battle armed gangs that have taken over the capital.

Conille's office said he would travel with Foreign Minister Dominique Dupuy, Finance Minister Ketleen Florestal and chief of staff Nesmy Manigat, while Justice Minister Carlos Hercule would stay as acting prime minister on his behalf.

"The delegation will have important work meetings with officials from international financial institutions, among others. It will also inspect Haiti's embassy in Washington," the office said, without giving further details.

A spokesperson for the U.S. National Security Council said Deputy National Security Advisor Jon Finer would meet with Conille on Monday.

The U.S. is the principal financial backer of a Kenya-led international security force the United Nations has ratified be sent to Haiti to help its police battle armed gangs that have plunged the country into a humanitarian crisis.

Haiti's former government first requested the force in 2022 and the a first deployment of Kenyan police arrived this week, though it is unclear when the rest of the force - expected to number over 2,500 - is set to arrive.

As armed khaki-clad Kenyan police in bullet-proof jackets and helmets patrolled the city in black armored vans, Port-au-Prince residents said they hoped the force could stop the indiscriminate killings and allow business to restart.

"We need peace. If the Kenyan police forces are here, it's so we can return to the lives we used to have. We hope they've come to work seriously," said resident Kloud Dine.

"We need the Kenyans here a while here because the gang members make us suffer too much," added Louise Baret, a painter. "Enough is enough."

In a video shared on social media on Wednesday, gang leader Jimmy "Barbecue" Cherizier rallied armed men, telling them to fire on Kenyan police and pledging to fight to the death: "I don't care if they are white or black. If they're not Haitian and they're on Haitian soil, they're invaders," he said.

Over half a million people have fled their homes due to the violence and around half the population is going hungry.

https://www.marketscreener.com/news/latest/Haiti-PM-travels-to-US-as-Kenyan-police-patrol-capital-47270200/

Woodcock, Marks at FDA forced Krause out to justify approvals for Biden vaccine mandates

 In revealing testimony in front of the House judiciary committee, Philip Krause, former Deputy Director of FDA vaccine products, testified that he was relieved of duty on COVID19 vaccines because the Biden administration wanted to rush FDA approval so they could push forth their fall 2021 vaccine mandates. Here is the key section

Krause explains the direct connection between forcing him out and the mandates.

Remember, the Biden vaccine mandates were issued only AFTER the CDC and administration knew the vaccine COULD NOT halt transmission. As such, the mandates were unethical— you can’t mandate a personal medical intervention for something that does not benefit 3rd parties, and furthermore, even if it did benefit 3rd parties, the benefits to third parties have to far outweigh loss of autonomy.

*Note: some people claim that a transient reduction in symptomatic covid19 is a benefit to third parties. This claim is laughable given just how weak the protection is, and just how short lived. In the universe of human interactions— it would make no difference to forcibly vaccinate a tiny fraction of people in one nation*

Given the vaccines were under EUA, the administration was eager to ram through full FDA approval so they could begin the mandates. When senior regulators Gruber and Krause suggested a slow, deliberative process, they were demoted.

Krause’s testimony shows the Biden administration engaged in inappropriate political tampering with the the FDA, and the FDA leaders— Woodcock and Marks— folded to political pressure. Marks in general has being doing a bad job at FDA, recently authorizing a sarepta product despite a failed P3 study and negative decision from the primary reviewers.

Finally, watch this video clip where Philip Krause explains the lofty rate of myocarditis in young men, confirming the Israeli estimate, consistent with my paper on the topic. In it, he also says he didn’t get a booster (good choice). And that natural immunity is more protective than the vaccine. The only mistake he makes is that there is no evidence that vaccinating a person who had COVID provides a further reduction in severe disease in someone who had COVID. That claim has never been validated in RCT.

Overall Philip Krause testimony revealed that the Biden administration did what Trump never did— tamper with the FDA to force vaccination on many people who didn’t need it (young/ those with prior COVID). It’s sad to realize that the Biden administration is full of many anti-science leaders, such as Murthy, Jha, and Walensky, several of whom pioneered this failed strategy.

As a result of the mandates, trust in public health is shredded and vaccine rates in children continue to fall.

Vinay Prasad, Hematology Oncology Medicine Health Policy Epidemiology Professor

https://www.drvinayprasad.com/p/woodcock-and-marks-at-fda-forced