Harpoon Update on the HPN217 Development and Option Agreement with AbbVie

 Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immuno-oncology company developing novel T cell engagers, announced today that AbbVie has notified the company that it will not exercise the exclusive license option of the parties’ Development and Option Agreement in connection with Harpoon’s HPN217 program, which targets B cell maturation antigen, or BCMA. ​The Agreement, which will terminate effective October 12, 2023, granted AbbVie an option to a worldwide, exclusive license to the HPN217 program. The program has been and will remain exclusively owned by Harpoon, and the company plans to complete the ongoing Phase 1 clinical trial with data to support the next phase of development.

https://finance.yahoo.com/news/harpoon-therapeutics-provides-hpn217-development-200500236.html

GoodRx, MedImpact Program to Ensure Seamless Access to Affordable Prescriptions

 GoodRx (NASDAQ: GDRX), a leading resource for healthcare savings and information, and MedImpact, the independent pharmacy benefit manager (PBM) and health solutions company, today announced a new savings solution designed to integrate GoodRx’s prescription pricing in a seamless experience at the pharmacy counter. Now, when an eligible MedImpact member fills a prescription for a generic medication, it will automatically compare their benefit and the GoodRx price and then deliver the lowest one. The amount paid will be applied to the member’s deductible.

"This solution allows us to meet Americans where they are by providing them with low prices on their prescriptions without the need for them to compare costs on their own," said Cynthia Meiners, Strategic Program Development Officer at GoodRx. "We are bringing together the best of what GoodRx does with the best of what MedImpact does to make it incredibly convenient for MedImpact’s members to start and stay on their prescribed treatments, and to fully integrate their clinical data. We truly feel the future of healthcare lies in these types of integrations."

The collaboration achieved by integrating GoodRx’s price comparison technology with MedImpact’s advanced technology platform allows both companies to deliver more savings without any additional work on the part of the consumer. In addition, members will benefit from the seamless data integration this program provides. Through MedImpact’s rigorous drug safety review, which includes thousands of health and safety checks, patients will be alerted about any negative drug interactions.

https://finance.yahoo.com/news/goodrx-medimpact-announce-program-ensure-130000982.html

'Atypical Antipsychotics No Safer Than Haloperidol for Post-Op Delirium: Study'

 A new study published in the Annals of Internal Medicine found atypical antipsychotics were not safer than haloperidol when it comes to treating postoperative delirium in older patients.

Dr Dae Hyun Kim

Dae Hyun Kim, MD, ScD, associate professor of medicine at Harvard Medical School, in Boston, who is the lead author of the study, said the findings were especially relevant, as the use of atypical antipsychotics, such as quetiapine, olanzapine, and risperidone, has increased while use of haloperidol has fallen.

A separate but related study led by Kim, which was recently published in the Journal of the American Geriatrics Society, showed that between 2008 and 2018, use of haloperidol and benzodiazepines in community hospitals and academic medical centers decreased while use of atypical antipsychotics, antidepressants, antiepileptics, and dexmedetomidine rose (P < .01).

"Clinicians should not think atypical antipsychotics are the safer option to haloperidol," Kim said. "We should focus on reducing prescriptions."

Postoperative Delirium

Postoperative delirium is the among the most common complications of surgery in older adults, affecting between 15% and 50% of those patients who undergo major operations. Postoperative delirium is associated with longer hospital stays, poor functional recovery, institutionalization, dementia, and death.

According to research from Harvard Medical School, postoperative delirium is linked to a 40% faster rate of cognitive decline among patients who develop the condition compared to those who do not experience the complication.

While older patients often feel tired or a bit off after surgery, marked changes in mental function, such as confusion, disorientation, agitation, aggression, hallucinations, or persistent sleepiness, could indicate postoperative delirium.

"Antipsychotic medications are most commonly used off label for managing those symptoms of delirium," Kim said. "What we've done is look at the comparative safety of two other drugs."

Results

In the retrospective cohort study, researchers analyzed data from 17,115 patients aged 65 years and older who were without psychiatric disorders and who received oral antipsychotics after major surgery requiring general anesthesia.

"These results don't apply to people in emergent situations where there is severe behavior that threatens their safety and others," Kim noted.

There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%), olanzapine (2.8%; relative risk [RR], 0.74; 95% CI, 0.42 – 1.27), quetiapine (2.6%; RR, 0.70; 95% CI, 0.47 – 1.04), or risperidone (3.3%; RR, 0.90; CI: 0.53, 1.41).

The study also found statistically insignificant differences in the risk for nonfatal clinical events. Those risks ranged from 2% to 2.6% for a cardiac arrhythmia, 4.2% to 4.6% for pneumonia, and 0.6% to 1.2% for strokes or transient ischemic attacks.

Dr Esther Oh

Esther Oh, MD, PhD, an associate professor at Johns Hopkins University School of Medicine, in Baltimore, said that caring for patients who experience acute changes in mental status or behaviors during hospitalization can be difficult.

"Although there is a lot of evidence in the literature that nonpharmacological methods to address these problems are effective, staff shortages of recent years have made it even more difficult for the care team to institute these methods," Oh told Medscape Medical News.

Prevention

Oh and Kim agreed that nonpharmacologic strategies, such as ensuring good nutrition and hydration, daily walking, cognitive-stimulating activities, and good sleep hygiene, are effective and safe in preventing postoperative delirium.

"These are common sense interventions, but they require a lot of staffing and training," Kim said. "It's a resource-intensive intervention that requires really changing the way hospital staff interacts with older patients in the hospital."

Second-generation antipsychotic medications often are thought to be safer than haloperidol in terms of side effects, Oh said, but the new findings challenge that assumption.

"Based on the findings from this study and on prior studies of antipsychotic use for older adults, use of all antipsychotics, both first and second generation, should be reviewed carefully to ensure they are being administered at the lowest effective dose for the shortest duration possible," she said.

The study was supported by the National Institute on Aging of the National Institutes of Health. Kim and Oh have disclosed no relevant financial relationships.

Ann Intern Med. Published online September 5, 2023. Abstract

https://www.medscape.com/viewarticle/996392

White House urges news networks to increase scrutiny of GOP’s Biden impeachment inquiry

 The White House has sent a memo to news outlets, urging them to ramp up scrutiny of the House Republicans’ impeachment inquiry into President Biden.

The memo, titled “It’s Time For The Media To Do More To Scrutinize House Republicans’ Demonstrably False Claims That They’re Basing Impeachment Stunt On,” was sent by Ian Sams, White House spokesperson for oversight and investigations.The attempt to pressure the media comes a day after Speaker Kevin McCarthy’s (R-Calif.) moved Tuesday to direct House committees to open a formal impeachment inquiry into Biden, and underscores how the impeachment drive is likely to be a major factor as the White House and GOP leaders gear up for next year’s elections.

The fight could also be an issue as Congress and the White House battle over funding the government. Lawmakers face a Sept. 30 deadline to prevent a shutdown.

The Hill was among the organizations that received the memo, which criticized the press for focusing more on the process of the impeachment drive in the House than on its substance.

The House investigations have centered on President Biden’s son Hunter Biden and his business dealings in Ukraine. The House Oversight and Accountability Committee has not found that the president directly financially benefited from his son’s business or proved that he made any policy decisions because of them.

Hunter Biden was expected to formally plead guilty over the summer to two misdemeanor charges related to his failure to pay taxes, but that plea deal fell apart during his initial court appearance on the matter when a judge questioned the parameters of the agreement. A special counsel has since been appointed to look into the case.

“[R]eporting that solely focuses on process rather than substance is woefully inadequate when it comes to something as historically grave as impeachment,” Sams wrote.

“It’s time for the media to ramp up its scrutiny of House Republicans for opening an impeachment inquiry based on lies,” the memo continued. “When even House Republican members are admitting that there is simply no evidence that Joe Biden did anything wrong, much less impeachable, that should set off alarm bells for news organizations.”

The impeachment drive by the House GOP has divided the Republican Party, with a number of Senate Republicans making it clear they oppose the effort and think it lacks evidence.

McCarthy decided to go forward with the inquiry without a vote, a reversal from his earlier position.

Sams separately Tuesday shared a letter from McCarthy to former Speaker Nancy Pelosi (D-Calif.) from 2019, during the impeachment proceedings into former President Trump, to highlight that McCarthy pushed back on her moves at the time to open an inquiry without a vote.

The White House memo argues that news organizations are doing a disservice to the American public by covering impeachment just as a “a process story” and “Republicans say X, but the White House says Y.”

“And in the modern media environment, where every day liars and hucksters peddle disinformation and lies everywhere from Facebook to Fox, process stories that fail to unpack the illegitimacy of the claims on which House Republicans are basing all their actions only serve to generate confusion, put false premises in people’s feeds, and obscure the truth,” Sams wrote.

The memo also included a document outlining what the White House said were “false claims” from lawmakers about Biden and his son Hunter Biden.

The White House has long been adamant that the president was not in business with his son, and the president has said himself that he never talked with Hunter Biden about his business dealings.

McCarthy’s formal endorsement of impeachment comes after weeks of him saying that he thought the House probes would eventually develop into an impeachment inquiry.

https://thehill.com/homenews/4201615-white-house-urges-news-networks-to-increase-scrutiny-of-gops-biden-impeachment-inquiry/

Moderna Scales Back COVID Vaccine Production, Pursues mRNA Medicines Plan

 Determined to expand its product pipeline beyond COVID-19 vaccines, Moderna on Wednesday announced a strategic plan with expectations to launch up to 15 new products across cancer as well as rare and infectious diseases over the next five years. 

Moderna provided Wednesday’s business and clinical updates as part of the company’s annual R&D Day in which it reinforced an mRNA-based approach “to create medicines addressing high unmet needs at unprecedented speed and efficiency.” 

However, after explosive growth during the coronavirus pandemic, Moderna’s shares have been sliding all year as sales wane for COVID vaccines, the biotech’s only approved product. Stock prices are down over 40% year-to-date, a trend CEO Stéphane Bancel is determined to turn around.  

An updated version of its COVID vaccine was approved by the FDA earlier this week, and sales for 2023 are expected to bring in $6 billion to $8 billion. At the same time, Moderna is downsizing its manufacturing footprint to help reach the company's gross margin growth goal of 75% to 80%. 

The company is promoting a slew of new mRNA-technology vaccines across respiratory, oncology and infectious disease. Its RSV vaccine is in the lead having already been submitted to authorities for approval. The mRNA-1345 vaccine is for the prevention of RSV-associated lower respiratory tract disease and acute respiratory disease in adults over 60, a particularly vulnerable population. Moderna used its Priority Review Voucher with the FDA to move up in line and are expecting a PDUFA date of April 2024. 

After a rocky Phase III for its seasonal flu vaccine, Moderna updated its mRNA-1010 formulation and tried again. An interim analysis of the P303 study revealed better results with mRNA-1010 meeting all co-primary endpoints across all four A and B strains of influenza. Separate Phase I/II data showed a higher level of antibody titers than GSK’s vaccine Fluarix. 

Moderna expects to meet with regulators soon, with hopes of a potential flu vaccine launch as soon as next year, Bancel told Fierce Biotech.  

The goal going forward is to combine the shots with a flu and COVID vaccine launch as soon as 2025. The following year, the plan is for a potential triple shot combining Moderna’s COVID, flu and RSV vaccines. 

Moderna’s latent and other virus vaccine pipeline includes candidates for cytomegalovirus, Epstein Barr, herpes simplex, varicella zoster virus, norovirus and HIV. According to the company, the market size for these diseases is between $10 billion and $25 billion. Its cytomegalovirus vaccine is in a pivotal Phase III study. 

The biotech has partnered with Merck for its cancer vaccine pipeline. Referred to as an individualized neoantigen therapy (INT), Moderna’s adjuvant shot is being coupled with Merck’s blockbuster Keytruda in clinical studies. Phase II and III trials are underway in patients with resected melanoma at different stages, while a Phase III trial in non-small cell lung cancer is coming soon. Development is planned to expand into additional tumor types.  

Other oncology vaccines and a rare disease portfolio are also progressing, according to Moderna, whose goal is to launch 15 new products and bring up to 50 new candidates into clinical trials over the next five years.  

Its oncology, rare and latent disease products are expected to increase annual sales by $10 billion to $15 billion in 2028, adding to the $8 billion to $15 billion expected from the respiratory franchise by 2027.

From 2024 to 2028, Moderna has allotted $25 billion for R&D as the company looks to “continue to invest in science to expand the field of mRNA medicine into new frontiers.”  

https://www.biospace.com/article/moderna-scales-back-covid-vaccine-production-pursues-mrna-medicines-/

Madrigal: NDA Acceptance, Priority Review for Resmetirom for NASH

Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), today announced that the U.S. Food and Drug Administration (FDA) has accepted for review its New Drug Application (NDA) for resmetirom for the treatment of adult patients with NASH with liver fibrosis. The FDA has granted Priority Review and assigned a Prescription Drug User Fee Act date for resmetirom of March 14, 2024, the target date by which the FDA intends to complete its review and take action on the NDA. The Agency noted that it is not currently planning to hold an advisory committee meeting to discuss the application.

https://finance.yahoo.com/news/madrigal-pharmaceuticals-announces-nda-acceptance-131000087.html

"We Need To See Pain... Unemployment Has To Jump 40–50%"

 By Benjamin Picton, Senior Macro Strategist at Rabobank

Concerns over price pressures have again been raised over the last 24 hours as we approach the release of the US CPI today. Again, this was most obvious in the crude oil market, where Brent continued its recent bull run to close above $92/bbl following the release of estimates from OPEC+ that the world faces a 3.3m barrel daily shortfall in the final quarter of the year (which echoed what Zerohedge said one week earlier).

Front-month European gasoil futures managed to close above $1000/mt, the highest level since late January when the DXY Dollar index was trading around 102, compared to 104 today. This comes as European diesel imports are on track to hit the highest levels in 8 months.

While oil and diesel prices were hitting new highs, stocks headed lower. The S&P500 lost 0.57% and the more duration-sensitive NASDAQ was down more than 1%, despite 10-year Treasury yields actually pulling back slightly on the day. The German ZEW survey saw respondents a little more upbeat on the future prospects of the economy, but they ranked current conditions as being every bit as bad as they were during the Covid lockdowns (!) The US curve flattened as higher energy prices were priced into short-end yields, but moves in yields over the last few days have been relatively muted (albeit usually higher), so I think it’s fair to say that the market is sweating on the release of that US CPI report before it strikes out confidently in either direction.

The moves in commodity prices have not been lost on one of our favouite bears, Jeremy Grantham. The famed British hedge fund manager spoke virtually to a conference in Sydney yesterday, where he lived up to his billing by saying that US equities were in an AI hype-driven speculative bubble, the probability of a US recession is 70% and that he would be “very careful with real estate all over the world” given that a multi-decade bull market in bonds has driven valuations to “crushingly high multiples of family income”. Grantham singled out commodities as the investment bright spot by suggesting that we now live in a “world of shortages” and that “we are not going to be rolling in commodities ever again.” “We don’t have enough metal to green the world economy... we don’t have enough lithium, cobalt, nickel or copper.”

On the same day that Grantham was speaking, property developer Tim Gurner was also giving his two cents worth at a conference across town. Gurner sparked outrage on the platform formerly known as Twitter by saying that “unemployment has to jump 40 – 50 percent in my view. We need to see pain in the economy... We need to remind people that they work for the employer, not the other way around... Tradies have definitely pulled back on productivity. They have been paid a lot to do not too much in the last few years, and we need to see that change.”

Gurner is known for his controversial takes, but this was a doozy. He’s not Robinson Crusoe in his view though. Incoming RBA Governor Michele Bullock gave a speech back in June where she suggested that the unemployment rate needed to rise to around 4.5% (her estimate of the NAIRU) for inflation to stabilize. We also had some hawkish comments from the BOE’s Catherine Mann recently, where she said that she “would rather err on the side of over-tightening” and that “in my view, holding rates at the current level risks enabling further inflation persistence.” Mann’s comments provide an interesting contrast to Nick TImiraos contention in the Wall Street Journal over the weekend that Fed officials are now broadly happy to err on the side of doing too little, rather than too much.

Mann’s comments might have been timely given the release of the UK labour market report yesterday, which showed year-on-year average weekly earnings were up by 8.5% in July, well above the already spicy 8.2% predicted by the Bloomberg survey. Stefan Koopman, our Senior Macro Strategist covering the UK, released a piece on factor shares last week arguing that neither capital nor labour has the upper hand at present, and that a recession might be just the ticket to sort out the inflation problem. So, maybe Gurner wasn’t too far off the mark?

Whatever the case, animosity between capital and labor is clearly growing and we are seeing workers becoming increasingly assertive in demanding a greater share of the income pie. Who can blame them? As Jeremy Grantham points out, most of gains in labor productivity in recent times have found their way into the pockets of the wealthy, rather than the pockets of workers, and when you can’t buy even a modest home on a solidly middle-class salary, you start to suspect something might be crook.

You don’t have to look far for evidence of this animosity. 140,000 United Auto Workers union members are threatening strike action this week unless the big 3 Detroit automakers accede to their demands for higher pay and improved working conditions. The timing is awkward given the competition automakers face from cheap EVs imported from China, and the worries that central bankers have over cost-push inflation. But the union points to strong profitability in recent years and says it’s time for the companies to pay up. Similar potential strike action by employees on Chevron’s Wheatstone LNG facility in Northern Australia has been giving Dutch TTF natural gas prices palpitations in recent times as potential interruptions to supply work their way through an already tightly constrained global market. Clearly (some) workers now have a lot of leverage, and they are willing to use it to get a better deal.

While all of this is going on, the central Government in Australia is attempting to pass new legislation through the parliament dubbed ‘Same Job, Same Pay’ that is intended to curtail the practice of using labour hire firms to undercut wages, provide right of entry to workplaces for union officials and introduce employee-like wages and conditions for contractors in the gig economy. Business groups, naturally, are united in their condemnation of the proposed changes, but the people who should be most worried are central bankers like Bullock, who have inexplicably lowered their estimates of the NAIRU over the last few years despite clear signs (like this) that labor markets are becoming more rigid, not less. This is a risk I flagged earlier in the year here.

So, for the time being we wait to see what the US CPI report will bring. Are we going to see further price pressures in services? And if we do, will that mean that Nick Timiraos’ “Important Shift in Fed Officials’ Rate Stance’ is short-lived and that Loretta Mester and Catherine Mann have been right all along? Whatever the case, tensions between labor and capital will continue to simmer away.

https://www.zerohedge.com/markets/we-need-see-pain-unemployment-has-jump-40-50