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Saturday, June 29, 2024

Autoimmune biotech Artiva Biotherapeutics refiles for a $100 million IPO, following attempt in 2021

 Artiva Biotherapeutics, a Phase 1 biotech developing off-the-shelf natural killer cell-based therapies for autoimmune diseases, filed on Friday with the SEC to raise up to $100 million in an initial public offering. The company had previously filed for an IPO in 2021, but ultimately withdrew the offering in late 2022. It never set terms.


Artiva is focused on developing natural killer (NK) cell-based therapies for patients suffering from autoimmune diseases and cancers. Its candidates are derived from donor cells (allogeneic) rather than a patient's own cells (autologous) and are pre-manufactured, stored frozen, and ready to ship, making them what it believes to be "off-the-shelf." Its lead candidate, AlloNK, is currently in an ongoing Phase 1/1b trial in lupus nephritis and a basket investigator-initiated trial in multiple autoimmune indications. Artiva expects to report initial data from at least one of these trials in the 1H25.

The San Diego, CA-based company was founded in 2019 and booked $33 million in collaboration and license revenue for the 12 months ended March 31, 2024. It plans to list on the Nasdaq under the symbol ARTV. Artiva Biotherapeutics filed confidentially on May 3, 2024. Jefferies, TD Cowen, and Cantor Fitzgerald are the joint bookrunners on the deal. No pricing terms were disclosed.

Why Won't The US Help Negotiate A Peaceful End To The War In Ukraine?

 by Jeffrey Sachs via AntiWar.com,

For the fifth time since 2008, Russia has proposed to negotiate with the U.S. over security arrangements, this time in proposals made by President Vladimir Putin on June 14, 2024. Four previous times, the U.S. rejected the offer of negotiations in favor of a neocon strategy to weaken or dismember Russia through war and covert operations.

The U.S. neocon tactics have failed disastrously, devastating Ukraine in the process, and endangering the whole world.

After all the warmongering, it’s time for Biden to open negotiations for peace with Russia.

Since the end of the Cold War, the U.S. grand strategy has been to weaken Russia. As early as 1992, then Defense Secretary Richard Cheney opined that following the 1991 demise of the Soviet Union, Russia too should be dismembered. Zbigniew Brzezinski opined in 1997 that Russia should be divided into three loosely confederated entities in Russian Europe, Siberia, and the far east. In 1999, the U.S.-led NATO alliance bombed Russia’s ally, Serbia, for 78 days in order to break Serbia apart and install a massive NATO military base in breakaway Kosovo. Leaders of the U.S. military-industrial complex vociferously supported the Chechen war against Russia in the early 2000s.

To secure these U.S. advances against Russia, Washington aggressively pushed NATO enlargement, despite promises to Mikhail Gorbachev and Boris Yeltsin that NATO would not move one inch eastward from Germany. Most tendentiously, the U.S. pushed NATO enlargement to Ukraine and Georgia, with the idea of surrounding Russia’s naval fleet in Sevastopol, Crimea with NATO states: Ukraine, Romania (NATO member 2004), Bulgaria (NATO member 2004), Turkey (NATO member 1952), and Georgia, an idea straight from the playbook of the British Empire in the Crimean War (1853-6).

Brzezinski spelled out a chronology of NATO enlargement in 1997, including NATO membership of Ukraine during 2005-2010. The U.S. in fact proposed NATO membership for Ukraine and Georgia at the 2008 NATO Bucharest Summit. By 2020, NATO had in fact enlarged by 14 countries in Central Europe, Eastern Europe, and the former Soviet Union (Czech Republic, Hungary, and Poland in 1999; Bulgaria, Estonia, Latvia, Lithuania, Romania, Slovakia, and Slovenia in 2004; Albania and Croatia, 2009; Montenegro, 2017; and Northern Macedonia, 2020), while promising future membership to Ukraine and Georgia.

In short, the 30-year U.S. project, hatched originally by Cheney and the neocons, and carried forward consistently since then, has been to weaken or even dismember Russia, surround Russia with NATO forces, and depict Russia as the belligerent power.

It is against this grim backdrop that Russian leaders have repeatedly proposed to negotiate security arrangements with Europe and the U.S. that would provide security for all countries concerned, not just the NATO bloc. Guided by the neocon game plan, the U.S. has refused to negotiate on every occasion, while trying to pin the blame on Russia for the lack of negotiations.

In June 2008, as the U.S. prepared to expand NATO to Ukraine and Georgia, Russian President Dmitry Medvedev proposed a European Security Treaty, calling for collective security and an end to NATO’s unilateralism. Suffice it to say, the U.S. showed no interest whatsoever in Russia’s proposals, and instead proceeded with its long-held plans for NATO enlargement.

The second Russian proposal for negotiations came from Putin following the violent overthrow of Ukraine’s President Viktor Yanukovych in February 2014, with the active complicity if not outright leadership of the U.S. government. I happened to see the U.S. complicity up close, as the post-coup government invited me for urgent economic discussions. When I arrived in Kiev, I was taken to the Maidan, where I was told directly about U.S. funding of the Maidan protest.

The evidence of U.S. complicity in the coup is overwhelming. Assistant Secretary of State Victoria Nuland was caught on a phone line in January 2014 plotting the change of government in Ukraine. Meanwhile, U.S. Senators went personally to Kiev to stir up the protests (akin to Chinese or Russian political leaders coming to DC on January 6, 2021 to rile up the crowds). On February 21, 2014, the Europeans, U.S., and Russia brokered a deal with Yanukovych in which Yanukovich agreed to early elections. Yet the coup leaders reneged on the deal the same day, took over government buildings, threatened more violence, and deposed Yanukovych the next day. The U.S. supported the coup and immediately extended recognition to the new government.

In my view, this was a standard CIA-led covert regime change operation, of which there have been several dozen around the world, including sixty-four episodes between 1947 and 1989 meticulously documented by Professor Lindsey O’Rourke. Covert regime-change operations are of course not really hidden from view, but the U.S. government vociferously denies its role, keeps all documents highly confidential, and systematically gaslights the world: “Do not believe what you see plainly with your own eyes! The U.S. had nothing to do with this.” Details of the operations eventually emerge, however, through eyewitnesses, whistleblowers, the forced release of documents under the Freedom of Information Act, declassification of papers after years or decades, and memoirs, but all far too late for real accountability.

In any event, the violent coup induced the ethnic-Russia Donbas region of Eastern Ukraine to break from the coup leaders, many of whom were extreme Russophobic nationalists, and some in violent groups with a history of Nazi SS links in the past. Almost immediately, the coup leaders took steps to repress the use of the Russian language even in the Russian-speaking Donbas. In the following months and years, the government in Kiev launched a military campaign to retake the breakaway regions, deploying neo-Nazi paramilitary units and U.S. arms.

In the course of 2014, Putin called repeatedly for a negotiated peace, and this led to the Minsk II Agreement in February 2015 based on autonomy of the Donbas and an end to violence by both sides. Russia did not claim the Donbas as Russian territory, but instead called for autonomy and the protection of ethnic Russians within Ukraine. The UN Security Council endorsed the Minsk II agreement, but the U.S. neocons privately subverted it. Years later, Chancellor Angela Merkel blurted out the truth. The Western side treated the agreement not as a solemn treaty but as a delaying tactic to “give Ukraine time” to build its military strength. In the meantime, around 14,000 people died in the fighting in Donbas between 2014 and 2021.

Following the definitive collapse of the Minsk II agreement, Putin again proposed negotiations with the U.S. in December 2021. By that point, the issues went even beyond NATO enlargement to include fundamental issues of nuclear armaments. Step by step, the U.S. neocons had abandoned nuclear arms control with Russia, with the U.S. unilaterally abandoning the Anti-Ballistic Missile (ABM) Treaty in 2002, placing Aegis missiles in Poland and Romania in 2010 onwards, and walking out of the Intermediate Nuclear Force (INF) Treaty in 2019.

In view of these dire concerns, Putin put on the table on December 15, 2021 a draft “Treaty between the United States of America and the Russian Federation on Security Guarantees.” The most immediate issue on the table (Article 4 of the draft treaty) was the end of the U.S. attempt to expand NATO to Ukraine. I called U.S. National Security Advisor Jake Sullivan at the end of 2021 to try to convince the Biden White House to enter the negotiations. My main advice was to avoid a war in Ukraine by accepting Ukraine’s neutrality, rather than NATO membership, which was a bright red line for Russia.

The White House flatly rejected the advice, claiming remarkably (and obtusely) that NATO’s enlargement to Ukraine was none of Russia’s business! Yet what would the U.S. say if some country in the Western hemisphere decided to host Chinese or Russian bases? Would the White House, State Department, or Congress say, “That’s just fine, that’s a matter of concern only to Russia or China and the host country?” No. The world nearly came to nuclear Armageddon in 1962 when the Soviet Union placed nuclear missiles in Cuba and the U.S. imposed a naval quarantine and threatened war unless the Russians removed the missiles. The U.S. military alliance does not belong in Ukraine any more than the Russian or Chinese military belongs close to the U.S. border.

The fourth offer of Putin to negotiate came in March 2022, when Russia and Ukraine nearly closed a peace deal just weeks after the start of Russia’s special military operation that began on February 24, 2022. Russia, once again, was after one big thing: Ukraine’s neutrality, i.e., no NATO membership and no hosting of U.S. missiles on Russia’s border.

Ukraine’s President Vladimir Zelensky quickly accepted Ukraine’s neutrality, and Ukraine and Russia exchanged papers, with the skillful mediation of the Foreign Ministry of Turkey. Then suddenly, at the end of March, Ukraine abandoned the negotiations.

U.K. Prime Minister Boris Johnson, following in the tradition of British anti-Russian war-mongering dating back to the Crimean War (1853-6), actually flew to Kiev to warn Zelensky against neutrality and the importance of Ukraine defeating Russia on the battlefield. Since that date, Ukraine has lost around 500,000 dead and is on the ropes on the battlefield.

Now we have Russia’s fifth offer of negotiations, explained clearly and cogently by Putin himself in his speech to diplomats at the Russian Foreign Ministry on June 14. Putin laid out Russia’s proposed terms to end the war in Ukraine.

“Ukraine should adopt a neutral, non-aligned status, be nuclear- free, and undergo demilitarization and de-nazification,” Putin said. “These parameters were broadly agreed upon during the Istanbul negotiations in 2022, including specific details on demilitarization such as the agreed numbers of tanks and other military equipment. We reached consensus on all points.

“Certainly, the rights, freedoms, and interests of Russian-speaking citizens in Ukraine must be fully protected,” he continued. “The new territorial realities, including the status of Crimea, Sevastopol, Donetsk and Lugansk people’s republics, Kherson, and Zaporozhye regions as parts of the Russian Federation, should be acknowledged. These foundational principles need to be formalized through fundamental international agreements in the future. Naturally, this entails the removal of all Western sanctions against Russia as well.”

Let me say a few words about negotiating.

Russia’s proposals should now be met at the negotiating table by proposals from the U.S. and Ukraine. The White House is dead wrong to evade negotiations just because of disagreements with Russia’s proposals. It should put up its own proposals and get down to the business of negotiating an end to the war.

There are three core issues for Russia:

  1. Ukraine’s neutrality (non-NATO enlargement),

  2. Crimea remaining in Russian hands, and

  3. boundary changes in Eastern and Southern Ukraine.

The first two are almost surely non-negotiable.

The end of NATO enlargement is the fundamental casus belli. Crimea is also core for Russia, as Crimea has been home to Russia’s Black Sea fleet since 1783 and is fundamental to Russia’s national security.

The third core issue, the borders of Eastern and Southern Ukraine, will be a key point of negotiations. The U.S. cannot pretend that borders are sacrosanct after NATO bombed Serbia in 1999 to relinquish Kosovo, and after the U.S. pressured Sudan to relinquish South Sudan. Yes, Ukraine’s borders will be redrawn as the result of the 10 years of war, the situation on the battlefield, the choices of the local populations, and tradeoffs made at the negotiating table.

Biden needs to accept that negotiations are not a sign of weakness. As Kennedy put it, “Never negotiate out of fear, but never fear to negotiate.” Ronald Reagan famously described his own negotiating strategy using a Russian proverb, “Trust but verify.”

The neocon approach to Russia, delusional and hubristic from the start, lies in ruins. NATO will never enlarge to Ukraine and Georgia. Russia will not be toppled by a CIA covert operation. Ukraine is being horribly bloodied on the battlefield, often losing 1,000 or more dead and wounded in a single day. The failed neocon game plan brings us closer to nuclear Armageddon.

Yet Biden still refuses to negotiate. Following Putin’s speech, the U.S., NATO, and Ukraine firmly rejected negotiations once again. Biden and his team have still not relinquished the neocon fantasy of defeating Russia and expanding NATO to Ukraine.

The Ukrainian people have been lied to time and again by Zelensky and Biden and other leaders of NATO countries, who told them falsely and repeatedly that Ukraine would prevail on the battlefield and that there were no options to negotiate. Ukraine is now under martial law. The public is given no say about its own slaughter.

For the sake of Ukraine’s very survival, and to avoid nuclear war, the President of the United States has one overriding responsibility today: Negotiate.

https://www.zerohedge.com/geopolitical/why-wont-us-help-negotiate-peaceful-end-war-ukraine

Agenus Tumor Reductions in Neoadjuvant MSS Colon Cancer

  Agenus Inc.  (“Agenus”) (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers, today announced results from an investigator-sponsored trial (IST) of botensilimab and balstilimab (BOT/BAL) in the neoadjuvant setting for colon cancer. Data were presented at the 2024 European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress in Munich, Germany.

https://www.biospace.com/article/releases/significant-tumor-reductions-in-neoadjuvant-mss-colon-cancer-patients-treated-with-botensilimab-balstilimab-presented-at-esmo-gi-conference/

Friday, June 28, 2024

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  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  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  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  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