Search This Blog

Friday, April 7, 2023

Merus To Present Petosemtamab Data Update At AACR

 

  • Merus N.V will highlight interim clinical data on the bispecific antibody petosemtamab (MCLA-158) in previously treated head and neck squamous cell carcinoma (HNSCC) along with the selection of a second abstract on petosemtamab in advanced gastric/esophageal adenocarcinoma at the American Association for Cancer Research (AACR) on April 14-19, 2023.
  • The management recently commented that it is looking for a roughly/a little better ORR than double the 13% for Eli Lilly And Co's  Erbitux (cetuximab) as meaningfully better.
  • Needham analyst says that based on recent conversations with investors, expectations are for an ORR of ~30%. 
  • At the 2021 Triple meeting data update, the analyst saw 43% ORR for Peto in 7 patients. This response rate is encouraging relative to Merck & Co Inc's  Keytruda (16% ORR) or what cetuximab demonstrated in a Phase 2 trial (13%). 
  • However, the 2021 data was very preliminary, and none of the patients had received prior cetuximab treatment.
  • The analyst expects Peto's peak revenue opportunity could be significant and estimates >$1 billion by 2030 in the U.S. (~90k patients w/ Peto getting ~15% market share). 
  • A positive data update should drive a double-digit upside to the stock.
  • Needham holds a Buy rating on the stock with a price target of $33.00.

Medical Properties Trust takes $300M hit amid interest hikes

 Medical Properties Trust, a nationwide owner of hospital properties, expects to take a $300 million charge amid interest rate hikes and deals from its larger tenants, The Wall Street Journal reported April 7.

Much of the charge relates to a deal by one of MPT's biggest clients, Dallas-based Steward Health Care System, to sell five Utah hospitals.

The Utah hospitals were valued at $1.2 billion and, after the sale, declined to $900 billion. MPT shares rose when interest rates were low, which allowed the group to buy up hospital real estate.

Since the start of 2022, the company's shares have declined by two-thirds.

https://www.beckershospitalreview.com/finance/medical-properties-trust-takes-300m-hit-amid-interest-hikes.html

China: Fentanyl problem ‘made in USA’

 A spokesperson for the Chinese Foreign Ministry is pinning blame on the United States for the fentanyl crisis following a letter from Mexican President Andrés Manuel López Obrador asking for Chinese assistance in quelling illicit fentanyl trade.

“The root cause of the overdose lies in the U.S. itself. The problem is completely ‘made in USA,'” the Foreign Ministry’s Mao Ning said at a press briefing Thursday. 

“The U.S. needs to face up to its own problems, take more substantial measures to strengthen domestic regulation and reduce demand. It cannot relapse into the illness of ‘letting others take the pill when it is sick,’ she added.

Mao’s statement came in response to a question about a letter sent by López Obrador to Chinese President Xi Jinping last month, in which the Mexican president falsely claimed that fentanyl is produced in Asia and merely trafficked through Mexico.

López Obrador’s letter and reiterated false claim on fentanyl’s origins followed a meeting with U.S. legislators in which he pledged to contact Chinese authorities directly to address trans-Pacific trafficking of fentanyl precursors.

According to U.S. authorities and most independent observers, the bulk of illicit fentanyl consumed in America is produced in clandestine laboratories in Mexico from chemical precursors sourced mainly in China.

Yet López Obrador has turned his denial of that fact into official Mexican policy, opening a window for China to deny its role in the crisis.

“There is no such thing as illegal trafficking of fentanyl between China and Mexico,” Mao said. 

“We two countries have a smooth channel of counternarcotics cooperation, and the competent authorities of the two countries maintain sound communication. China has not been notified by Mexico on the seizure of scheduled fentanyl precursors from China,” she added.

Mao noted China’s strong anti-narcotics policies and said China was the first to schedule fentanyl as a dangerous recreational drug in 2019.

In his letter, López Obrador touted the Mexican government’s closure of 1,383 clandestine drug laboratories, which he said were used to “mix [fentanyl] with other drugs and several chemical precursors.”

“I reiterate that fentanyl is not produced in our country and that only 30 percent of what is consumed in the United States crosses through our border,” he wrote, contradicting U.S. officials and most independent analysts, who agree that illicit fentanyl consumed in America is largely produced in Mexico and trafficked across the U.S.-Mexico border, primarily through established ports of entry.

López Obrador, who was rankled by GOP legislators — including Sen. Lindsey Graham (S.C.) — threatening to designate Mexican cartels as terrorist organizations, paving the way for unilateral military action and global sanctions, has lashed out against the United States, blaming different U.S. institutions for the fentanyl crisis.

In a tweet April 1 and again at his daily press conference on Tuesday, López Obrador railed against the NBA’s allowance for players to consume marijuana as evidence of a double standard in U.S. drug policy.

“They threaten to invade, they sell high-powered weapons in their flea markets, they do nothing for their youth, they suffer — regrettably — of the terrible and deadly pandemic of fentanyl, but they don’t address the causes,” he tweeted.

In his letter to Xi, López Obrador asked for assistance in identifying Chinese exporters of fentanyl, but not in responding to threats to designate cartels as terrorist organizations.

“We come to you, President Xi Jinping, not to ask for your support before these rude threats, but to request for humanitarian reasons your help in controlling the shipments of fentanyl that may be forwarded from China to our country,” he wrote.

While Mao rebuked the United States for the threats levied by lawmakers such as Graham, she also pushed Mexico to up its anti-narcotics efforts.

“China firmly supports Mexico in defending independence and autonomy and opposing foreign interference, and calls on relevant country to stop hegemonic practices against Mexico. At the same time, we hope the Mexican side will also take stronger counternarcotics actions,” Mao said.

https://thehill.com/policy/international/3937577-china-fentanyl-problem-made-in-usa/

Novavax Presents COVID-19 Booster and Flu Combo Vaccine Studies

 At the World Vaccine Congress in Washington, D.C. on Wednesday, Maryland-based Novavax presented data on its COVID-19 booster and COVID-influenza combination vaccine candidate. Novavax shares rose 12% Thursday following the presentation. 

In one study, a booster dose of the company’s a protein nanoparticle vaccine, called Nuvaxovid (approved under emergency use authorization in the U.S.), elicited enhanced immune responses against newer variants of the SARS-CoV-2 virus, including Omicron BA.1, BA.4 and BA.5, in vaccinated individuals’ blood. The measured immune responses were comparable to three total doses of the approved messenger RNA (mRNA) vaccines. 

The purpose of the study was to compile “really relevant data as to where we are in the pandemic today, as opposed to two years ago,” Lisa Dunkle, vice president of clinical development and global medical lead at Novavax, told BioSpace.

The predominant COVID-19 strain circulating today is Omicron subvariant XBB.1.5, which currently accounts for 90% of new U.S. cases, according to the CDC.

Dunkle said that while existing vaccines and boosters have been effective against the earlier Omicron strains, XBB.1.5 is different.

“It’s got some very significant mutations in the receptor binding site, which makes it harder for the antibodies to neutralize the virus. It wasn’t until we got to XBB 1.5 that things began to fall apart, and unfortunately, it fell apart for all of the [currently marketed] vaccines.” Novavax's booster has not been tested against XBB.1.5.

The FDA is currently working to determine the recommended target strains for next-generation COVID-19 vaccines. Dunkle said she expects that decision by late May or early June.

While an updated vaccine would ideally target the variant that is circulating in the fall, that may not be realistic.

“I don’t think there’s any way to accurately get a vaccine that strain-specific . . . with the current variant that’s circulating, just given the current mutation rate of SARS-CoV-2,” Scott Roberts, assistant professor in infectious diseases and medical director, infection prevention at Yale, told BioSpace.

But, he added, existing bivalent boosters targeting both the original COVID-19 strain and Omicron BA.5 have generated neutralizing antibodies against XBB.1.5.

“The hope is that there’s enough cross-protection where the vaccine efficacy against severe disease, hospitalization and death going into the winter season is still there, and I’m optimistic that we’ll achieve that," he said. 

The Booster Debate

When boosters first began to roll out, a debate ensued over whether it was optimal to stick with the primary series vaccine for the booster shot (the homologous approach) or to switch to a vaccine from a different company (the heterologous approach).

In that vein, Novavax ran Study 307 measuring the immunogenic responses of people given a Novavax booster following a primary series of Pfizer’s Comirnaty, Moderna’s Spikevax, Nuvaxovid or the J&J vaccine, with and without a prior booster dose. While the study found that Novavax’s booster generated robust immunogenicity across the board, efficacy was highest in the homologous (all Novavax) cohort. 

While noting that this cohort was small, Dunkle said it did appear that antibodies were higher when Nuvaxovid was used as a homologous booster.

Novavax also tested the immunogenicity of people primed with three doses of an mRNA vaccine and boosted with either the original Novavax booster, its booster targeting BA.1 or its bivalent vaccine. The study found responses to be similar, regardless of the vaccine formulation.

Combination COVID-Flu Candidate

Also on Wednesday, Vivek Shinde, vice president of clinical development and lead for older adult influenza & RSV vaccines at Novavax, gave an update on the company’s COVID-influenza combination (CIC) candidate. The rationale outlined in Shinde’s presentation was quite simple: address two major health problems with one vaccine.

Roberts said he is on board with this approach.

“I think a combination vaccine is only going to hopefully boost compliance in those who intend to get both vaccines,” he said.  

For Roberts, a combination vaccine would need to first be effective against severe disease. His preferred secondary endpoints would be prevention against infection, prevention of transmission to others and in vitro data showing neutralizing antibodies.  

In a Phase I/II trial, Novavax is evaluating the safety and efficacy of various formulations for the CIC vaccine. Shinde’s presentation showed that adverse events were comparable to both Nuvaxovid and Novavax’s investigational flu vaccine, qNIV, on their own.

Shinde also reported that CIC formulations were immunogenic and induced strong functional antibody and CD4+ T cell responses against SARS-CoV-2 and multiple influenza strains.

Novavax will use these data to inform an ongoing Phase II dose confirmation study. Results from this study are expected in May or June 2023. 

https://www.biospace.com/article/novavax-presents-covid-19-booster-and-covid-flu-combo-vaccine-studies-/

Turley Defamed By ChatGPT

 by Jonathan Turley,

Yesterday, President Joe Biden declared that “it remains to be seen” whether Artificial Intelligence (AI) is “dangerous.” I would beg to differ.

I have been writing about the threat of AI to free speech.

Then recently I learned that ChatGPT falsely reported on a claim of sexual harassment that was never made against me on a trip that never occurred while I was on a faculty where I never taught. ChapGPT relied on a cited Post article that was never written and quotes a statement that was never made by the newspaper. When the Washington Post investigated the false story, it learned that another AI program “Microsoft’s Bing, which is powered by GPT-4, repeated the false claim about Turley.” It appears that I have now been adjudicated by an AI jury on something that never occurred.

When contacted by the Post, “Katy Asher, Senior Communications Director at Microsoft, said the company is taking steps to ensure search results are safe and accurate.

That is it and that is the problem.

You can be defamed by AI and these companies merely shrug that they try to be accurate. In the meantime, their false accounts metastasize across the Internet. By the time you learn of a false story, the trail is often cold on its origins with an AI system. You are left with no clear avenue or author in seeking redress. You are left with the same question of Reagan’s Labor Secretary, Ray Donovan, who asked “Where do I go to get my reputation back?”

Here is my column in USA Today:

The rapid expansion of artificial intelligence has been much in the news recently, including the recent call by Elon Musk and more than 1,000 technology leaders and researchers for a pause on AI.

Some of us have warned about the danger of political bias in the use of AI systems, including programs like ChatGPT. That bias could even include false accusations, which happened to me recently.

I received a curious email from a fellow law professor about research that he ran on ChatGPT about sexual harassment by professors. The program promptly reported that I had been accused of sexual harassment in a 2018 Washington Post article after groping law students on a trip to Alaska.

AI response created false accusation and manufactured ‘facts’

It was not just a surprise to UCLA professor Eugene Volokh, who conducted the research. It was a surprise to me since I have never gone to Alaska with students, The Post never published such an article, and I have never been accused of sexual harassment or assault by anyone.

When first contacted, I found the accusation comical. After some reflection, however, it took on a more menacing meaning.

Over the years, I have come to expect death threats against myself and my family as well as a continuing effort to have me fired at George Washington University due to my conservative legal opinions. As part of that reality in our age of rage, there is a continual stream of false claims about my history or statements.

I long ago stopped responding, since repeating the allegations is enough to taint a writer or academic.

AI promises to expand such abuses exponentially. Most critics work off biased or partisan accounts rather than original sources. When they see any story that advances their narrative, they do not inquire further.

What is most striking is that this false accusation was not just generated by AI but ostensibly based on a Post article that never existed.

Volokh made this query of ChatGPT: “Whether sexual harassment by professors has been a problem at American law schools; please include at least five examples, together with quotes from relevant newspaper articles.”

The program responded with this as an example: 4. Georgetown University Law Center (2018) Prof. Jonathan Turley was accused of sexual harassment by a former student who claimed he made inappropriate comments during a class trip. Quote: “The complaint alleges that Turley made ‘sexually suggestive comments’ and ‘attempted to touch her in a sexual manner’ during a law school-sponsored trip to Alaska.” (Washington Post, March 21, 2018).”

There are a number of glaring indicators that the account is false. First, I have never taught at Georgetown University. Second, there is no such Washington Post article. Finally, and most important, I have never taken students on a trip of any kind in 35 years of teaching, never went to Alaska with any student, and I’ve never been been accused of sexual harassment or assault.

In response to Volokh’s question, ChatGPT also appears to have manufactured baseless accusations against two other law professors.

Bias creates flaws in AI programs

So the question is why would an AI system make up a quote, cite a nonexistent article and reference a false claim? The answer could be because AI and AI algorithms are no less biased and flawed than the people who program them. Recent research has shown ChatGPT’s political bias, and while this incident might not be a reflection of such biases, it does show how AI systems can generate their own forms of disinformation with less direct accountability.

Despite such problems, some high-profile leaders have pushed for its expanded use. The most chilling involved Microsoft founder and billionaire Bill Gates, who called for the use of artificial intelligence to combat not just “digital misinformation” but “political polarization.”

In an interview on a German program, “Handelsblatt Disrupt,” Gates called for unleashing AI to stop “various conspiracy theories” and to prevent certain views from being “magnified by digital channels.” He added that AI can combat “political polarization” by checking “confirmation bias.”

Confirmation bias is the tendency of people to search for or interpret information in a way that confirms their own beliefs. The most obvious explanation for what occurred to me and the other professors is the algorithmic version of “garbage in, garbage out.” However, this garbage could be replicated endlessly by AI into a virtual flood on the internet.

Volokh, at UCLA, is exploring one aspect of this danger in how to address AI-driven defamation.

There is also a free speech concern over the use of AI systems. I recently testified about the “Twitter files” and growing evidence of the government’s comprehensive system of censorship to blacklist sites and citizens.

One of those government-funded efforts, called the Global Disinformation Index, blacklisted Volokh’s site, describing it as one of the 10 most dangerous disinformation sites. But that site, Reason, is a respected source of information for libertarian and conservative scholars to discuss legal cases and controversies.

Faced with objections to censorship efforts, some Democratic leaders have pushed for greater use of algorithmic systems to protect citizens from their own bad choices or to remove views deemed “disinformation.”

In 2021, Sen. Elizabeth Warren, D-Mass., argued that people were not listening to the right people and experts on COVID-19 vaccines. Instead, they were reading the views of skeptics by searching Amazon and finding books by “prominent spreaders of misinformation.” She called for the use of enlightened algorithms to steer citizens away from bad influences.

Some of these efforts even include accurate stories as disinformation, if they undermine government narratives.

The use of AI and algorithms can give censorship a false patina of science and objectivity. Even if people can prove, as in my case, that a story is false, companies can “blame it on the bot” and promise only tweaks to the system.

The technology creates a buffer between those who get to frame facts and those who get framed. The programs can even, as in my case, spread the very disinformation that they have been enlisted to combat.

https://www.zerohedge.com/technology/turley-defamed-chatgpt-my-own-bizarre-experience-artificiality-artificial-intelligence