- Axsome Therapeutics (NASDAQ:AXSM) closed up ~7% Tuesday, the same day that Cantor Fitzgerald reiterated an outperform rating and $108 price target (~42% upside based on Tuesday's close).
- Cantor mentioned the biopharma in its honorable mention list of neuro-innovator and platform-enabled therapeutics companies for H2 2023. The firm noted that a data readout for a phase 3 trial of AXS-12 for narcolepsy could boost the stock.
- Axsome (AXSM) is also benefitting from growing sales of its fast-acting antidepressant Auvelity (dextromethorphan and bupropion), which launched in October 2022. Per IQVIA, ~4.9K Auvelity scripts were written for the week ended Aug. 11, a 7% increase from the prior week.
Tuesday, August 22, 2023
Cantor repeats Buy on Axsome
Driverless cars are no place to relax, new study shows
Early data on activities that will be unsafe to undertake in automated vehicles has been released. From doing work to watching the world, from social media to resting -- preliminary results are in.
Research led by RMIT University looked at what happens if a driver is suddenly required to take control of an automated vehicle, such as in an emergency.
The series of papers examines how experience and three types of distractions (work, social media and rest) impacted on the driver's ability to respond.
Study lead author in the School of Engineering, Dr Neng Zhang, said authorities need to begin drafting policies to regulate the responsible use of automated vehicles before Level 3 and 4 automated vehicles appear on Australian roads.
While the National Transport Commission has outlined a regulatory framework for automated vehicles in Australia, driver training, licensing and obligations are still being considered.
Laying the road to regulation
There are five levels of vehicle automation. Already, Level 1 and Level 2 are common through features such as lane keeping, automated parking and cruise control. More advanced automated vehicles -- what we think of when we say 'driverless cars' -- are currently being trialled but are not yet commercially available in Australia.
"In Level 3 and 4 automated driving, the human driver will still need to respond in an emergency, taking control of the vehicle," said Zhang.
"This data is a starting place for regulation and could lead to data-backed legislation that ensures drivers are given enough time to respond quickly and flawlessly to emergency events."
A study of distraction
Using a Level 3 automated vehicle simulation, the researchers tested participants' speed and effectiveness in taking over the vehicle in the event of an emergency.
"We had them writing business emails (working condition), watching videos (entertaining condition), and taking a break with their eyes closed (resting condition)," said Zhang.
"These tasks required drivers to invest high, moderate, and low levels of mental workload. We tested their responses after a short interval (5 minutes) or long interval (30 minutes) of participating in one of these tasks. All of these tasks worsened the takeover and led to a period of poorer driving.
"We found that resting resulted in the worst takeover response, followed by working. Social media was less disruptive. However, the longer the participant engaged in an activity, the worse their response was to an emergency."
The cross-disciplinary research team brought together RMIT expertise in human body vibration, automotive engineering and cognitive psychology from the School of Engineering, School of Health and Biomedical Sciences and School of Science.
Biomedical researcher and author on the papers, Professor Stephen Robinson, warned that emergencies require a high level of cognition.
"As soon as something unexpected happens, such as a child running across the road, we need to be able to use our full cognitive abilities to assess the situation and take appropriate action," said Robinson.
"Takeover requests in automated vehicles occur when the onboard computer lacks the capacity to deal with changed or complex driving conditions. Such conditions are potentially dangerous and require the driver to focus quickly and act decisively to keep our roads safe."
Young drivers to struggle with emergency takeovers
In addition to distractions, the study looked at the experience of drivers with a focus on young people.
"We found that driving experience and takeover performance were highly correlated, with inexperienced drivers (with less than 20,000 kilometres of driving experience) responding more slowly and less effectively. The distance driven since gaining a driver's licence is more important than the number of years since the licence was issued," said Zhang.
"Our findings highlight the need for vehicle manufacturers and licencing authorities to develop solutions that ensure that conditionally automated vehicles are safe for drivers with varying experience levels."
Driving research to back legislation
The paper, "Is driving experience all that matters? Drivers' takeover performance in conditionally automated driving" (DOI 10.1016/j.jsr.2023.08.003), with lead author Neng Zhang, was published in the Journal of Safety Research this month.
It builds on "Influence of non-driving related tasks on driving performance after takeover transition in conditionally automated driving" (DOI 10.1016/j.trf.2023.05.009) published in Transportation Research Part F: Traffic Psychology and Behaviour in mid-2023.
The team is now investigating how to stimulate alertness and improve effectiveness of driver takeovers.
Engineering expert and author on the papers, Professor Mohammad Fard, explained that seamless and safe transition between vehicle automation and human is the goal.
"The aim of our work is to enhance 'human-automation interaction' for autonomous vehicles and significantly improve the way humans interact with and control these advanced autonomous vehicles, leading to enhanced efficiency and safety in their operation," said Fard.
However, there is a limit to what the engineering and design of autonomous vehicles can achieve. The researchers emphasised that regulations must also address issues such as distraction, alertness and experience before Level 3 automation can be successfully adopted in Australia.
"Governments can effectively safeguard road safety by acknowledging these detrimental effects and regulating non-driving activities in the context of autonomous driving."
Journal Reference:
- Neng Zhang, Mohammad Fard, John Laurence Davy, Sibashis Parida, Stephen R. Robinson. Is driving experience all that matters? Drivers’ takeover performance in conditionally automated driving. Journal of Safety Research, 2023; DOI: 10.1016/j.jsr.2023.08.003
Capsules surrounding liver metastases of colorectal cancer are healing response by the liver
A study by researchers from Karolinska Institutet and physicians from Karolinska Hospital shows that a capsule of connective tissue around liver metastases from colorectal cancer improves patient survival and represents a healing response by the liver, not a phenomenon caused by the tumor itself.
Metastases in the liver are common in many cancer types. Microscopic investigation of the invasion front of liver metastases has revealed distinctly different tissue architectures: Some metastases are surrounded by a capsule of connective tissue, while in others, tumor cells make direct contact with the liver cells. Patients whose metastases are surrounded by connective tissue have significantly superior survival.
Despite its strong impact on survival, the origin of the surrounding capsule has been unclear. The team of Marco Gerling's group at the Department of Biosciences and Nutrition, Karolinska Institutet, used clinical samples from patients with liver metastases to trace the origins of the capsule. They found that the capsule is similar to the type of liver fibrosis that develops in patients with non-cancer liver disease, where it develops as part of a reparative process. Using mouse models, they showed that the capsule develops when cancer cells fail to invade and replace healthy liver tissue.
Close collaboration between researchers and clinicians
"The collaborations between our basic research lab and the surgeons and pathologists at Karolinska University Hospital were instrumental for this study," says Marco Gerling, the lead author.
"We could connect observations made by our collaborating pathologists (Béla Bozóky and Carlos Fernández Moro) with extensive clinical data and functional studies in novel mouse models," he continues. "For the future, we are excited to learn more about how cancer cells invade into healthy tissue and we hope to soon learn how to inhibit this process to the benefit of our patients. I cannot stress enough that solving important questions in cancer research requires a close and constant exchange between basic researchers and clinicians."
Published in Nature Communications, the results are the first from the KaroLiver patient cohort, which includes more than 700 patients with liver metastases from colorectal cancer operated on at Karolinska University Hospital. The KaroLiver investigators are Jennie Engstrand (consultant surgeon and postdoc), Carlos Fernández Moro (consultant pathologist and postdoc) and Marco Gerling (resident physician in oncology and research group leader).
More information: Carlos Fernández Moro et al, An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver, Nature Communications (2023). DOI: 10.1038/s41467-023-40688-x
https://medicalxpress.com/news/2023-08-capsules-liver-metastases-colorectal-cancer.html
New approach to screening has potential to extend survival in glioblastoma brain cancer
A new form of screening may improve survival rates among people with a fast-growing type of brain tumor by helping identify those most likely to benefit from certain treatments.
Innovative preclinical research in mice models has shown that a molecular imaging technique can reveal the presence of a protein called PD-L1 in glioblastomas—the most common type of cancerous brain tumor in adults.
Alongside other measures, tests to detect high levels of PD-L1 could help direct treatment decisions, potentially leading to better patient outcomes.
Assessing PD-L1 expression levels
Currently, scientists assess PD-L1 expression levels by carrying out immunohistochemistry on samples of tissue taken from the patient during surgery, which is the first-line treatment for glioblastoma. However, this technique is subject to human error and is not standardized globally for these patients or this particular tumor. It can also be difficult to quantify the results.
Researchers at The Institute of Cancer Research have now shown that a non-invasive imaging technique called immuno-positron emission tomography (immuno-PET) could be a better approach. The research has been published in the journal Cancers.
Immunotherapy may improve the treatment landscape
Glioblastoma starts as a growth of cells in the brain. It grows quickly and typically spreads within the brain, making it very difficult to treat effectively. No cure is yet available, and patients who initially respond to treatment tend to experience relapse. The average survival time is just 12–18 months, with only 5% of patients surviving more than five years.
In recent years, immunotherapy has shown potential as a treatment for glioblastoma. In particular, researchers have been testing drugs called immune checkpoint inhibitors, which prevent other proteins from dampening the body's immune response. The results to date have been mixed, suggesting that the treatment is only likely to be effective for a subset of patients.
Creating a novel radiotracer
The ICR's team successfully used NOTA-maleinide to link ZPD-L1 affibody molecules to fluorine-18 and gallium-68 radionuclides. Affibodies are small proteins created to bind strongly to target proteins—in this case, PD-L1. This procedure created 18F-AIF-NOTA-ZPD-L1 and 68Ga-NOTA-ZPD-L1, which, with high specificity, recognize PD-L1 on tumor cells and in their microenvironment.
The team chose to use affibodies rather than antibodies because their much smaller size means that they clear the body far more quickly, minimizing the radiation dose for patients and preventing delays to surgery. Using affibodies also makes it possible to get high-quality images just one hour after injection. In comparison, when antibodies are used, the images are usually only retrieved after 48 hours.
Trialing the new approach
The researchers demonstrated that these radio-labeled affibodies could be used to assess the expression level of PD-L1 in tumors in mice. PET scans showed that although there was some uptake of the radiotracer in healthy tissue, the brain tumors were clearly visualized with high tumor-to-background contrast.
Then, the researchers looked into 36 samples from people with newly diagnosed glioblastoma. They noted PD-L1-positive membrane staining in 39% of the samples. A separate analysis of 161 human glioblastoma samples confirmed that tumors with a mesenchymal signature, which is linked to a better response to immune checkpoint inhibitors, had a significantly elevated expression level of PD-L1 compared with other glioblastoma subtypes. This supports the thinking that health care professionals could use immuno-PET to identify the patients most likely to benefit from immune checkpoint inhibitors.
The researchers hope that this work will lead to better outcomes for the 30%–49% of patients with the mesenchymal subtype of glioblastoma. They are now working on a clinical trial in Poland that builds on the foundations laid by this preclinical research and expect to present data from that trial in the near future.
Dr. Gabriela Kramer-Marek, Group Leader in Preclinical Molecular Imaging at the ICR, said, "It has been really exciting to see the journey from lab to clinic. We are currently running a clinical trial in people, which was only possible because of this promising preclinical work. The trial was the first ever to use immuno-PET to evaluate PD-L1 in people with primary glioblastoma, and we hope to see images that clearly show the presence of PD-L1 in these brain tumors.
"The treatment for glioblastoma has not changed for decades. Although we still do not have a cure, I believe that this new screening approach could definitely change patient outcomes."
More information: Gitanjali Sharma et al, Immuno-PET Imaging of Tumour PD-L1 Expression in Glioblastoma, Cancers (2023). DOI: 10.3390/cancers15123131
https://medicalxpress.com/news/2023-08-approach-screening-potential-survival-glioblastoma.html
MS: New approach for repairing damaged nerve sheaths
Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS). In Germany, more than 280,000 people are affected. In most cases, MS progresses in relapses, which occur completely irregularly as excessive inflammatory reactions in the spinal cord and brain. In the process, misdirected immune cells destroy the protective myelin sheaths of the nerve fibers and thus damage the nerves.
High-dose cortisone is usually used to slow down the inflammation. Preventive immunotherapy is also used to reduce the number and severity of attacks. It is true that the nerve fiber sheaths can be partially restored by the body's own repair processes. But this spontaneous remyelination usually proceeds incompletely in MS patients or fails to occur at all.
And to date, there is no drug that promotes this repair. Researchers from the Department of Neurology with Clinical Neurophysiology and the Institute of Clinical Biochemistry at the Hannover Medical School (MHH) have now discovered a naturally occurring mechanism that can be used to decisively improve the repair of the myelin sheaths.
Sugar compound activates immune cells of the brain
The focus here is on the microglial cells of the brain. In addition to their work as "rubbish collectors" for the removal of damaged cells and foreign bodies, the microglia also take on tasks for the immune response and constantly look for signs of injury or infection. If there is a problem, the microglial cells are activated and release cytokines and other signaling molecules.
This attracts other immune cells such as T and B cells, which normally reside outside the brain. The body's own sugar compound polysialic acid plays a crucial role in the activation of microglia. "The microglia has an immune receptor called Siglec-E that recognizes polysialic acid," explains biochemist Dr. Hauke Thiesler. If the sugar molecule binds to the receptor, the microglia cells switch from the state "pro-inflammatory" to "anti-inflammatory".
This regulatory mechanism can apparently also be controlled from outside. By externally adding polysialic acid to cultures with living tissue sections, the researchers were able to show that previously destroyed myelin sheaths were almost completely renewed as a result of an anti-inflammatory effect of polysialic acid on the microglia. The results are published in the journal Frontiers in Cellular Neuroscience.
Programming key cells for healing
"The microglial cells are the key cells that do the work directly on site and which we want to guide in a certain direction, so to speak, with the help of polysialic acid and thereby program them for healing," says the biochemist.
Because the destruction of the myelin sheaths and nerve cells has serious consequences that can affect all brain and spinal cord functions—but mainly the ability to move and coordinate, the sense of touch and the ability to see. For a large proportion of patients, multiple sclerosis brings severe disabilities.
"Activating the self-healing powers in the brain would be a promising support in MS therapy, which currently focuses exclusively on the immune system outside," says Dr. Lara-Jasmin Schröder from the Department of Neurology with Clinical Neurophysiology. "Those affected are usually 20 to 40 years old when clinical symptoms of MS first appear," says the medical biologist. This leaves plenty of time to intervene in the regeneration between MS attacks and prevent nerve damage.
Admittedly, the studies on the tissue section cultures have only limited significance. But the researchers are optimistic based on the "striking results" that myelin regulation also works in the living organism. "The advantage is that the Siglec-E receptor in the brain actually only sits on the microglia cells and the polysialic acid can therefore intervene there in a very targeted way," explains Dr. Thiesler.
And because the mechanism generally reduces inflammatory activity, the procedure could also be interesting for other neurodegenerative diseases, the biochemist suspects. Next, the research team would like to test the results in the animal model and use the MS expertise available in Lower Saxony for this.
More information: Lara-Jasmin Schröder et al, Polysialic acid promotes remyelination in cerebellar slice cultures by Siglec-E-dependent modulation of microglia polarization, Frontiers in Cellular Neuroscience (2023). DOI: 10.3389/fncel.2023.1207540
https://medicalxpress.com/news/2023-08-multiple-sclerosis-approach-nerve-sheaths.html
Ex-JPMorgan Gold Traders Get Prison for ‘Prolific Spoofing’
The former head of JPMorgan Chase & Co.’s precious-metals desk and his top trader were sentenced to prison for spoofing, fraud and attempted market manipulation.
Michael Nowak, who ran gold and silver trading at the bank, and trader Gregg Smith were sentenced Tuesday in Chicago by US District Judge Edmond Chang. Nowak received a term of one year and one day while Smith was given two years, the stiffest sentence yet in a recent government crackdown on questionable trading practices.
Both men were convicted at a trial last year. Smith, 59, was described as “the most prolific spoofer that the government has prosecuted to date” while Nowak, 49, has been called “the boss” behind the scheme.
In imposing sentence, the judge said Smith and Nowak clearly knew what they were doing was wrong.
“This is a serious offense that you committed,” Chang said to Nowak. “What happened here was the equivalent of putting out lies — and many lies — into the market. Market integrity is a crucial component to the financial markets. These lies moved the market. It’s not like they had zero impact.”
The prison sentences were intended to “send a message” that market manipulation will be punished, the judge said. “I’m trying to deter all forms of financial fraud in the market,” he said.
Chang ordered Nowak to start his sentence on Oct. 23 and Smith on Jan. 15. Lawyers for both men said they planned to appeal their convictions.
Smith and Nowak “used their positions as some of the most powerful traders in the worldwide precious metals markets to engage in an egregious effort to manipulate prices for their benefit,” Acting US Assistant Attorney General Nicole M. Argentieri said in a statement, adding the Justice Department was committed to holding “accountable those who engage in fraud and manipulation that undermines the investing public’s trust in the integrity of our commodities markets.”
Prosecutors had initially sought sentences of six years for Smith and five years for Nowak, but on Tuesday said they were revising those down to around two years. Both men’s lawyers argued that they should be spared jail because neither gained personally from the spoofing.
The JPMorgan case is part of a crackdown by federal prosecutors on illegal spoofing, where traders place bogus orders to move prices up or down and then quickly cancel them before they can be executed. Smith and Nowak used the technique to manipulate gold and silver prices from 2008 to 2016.
Convictions for Smith, Nowak and a third trader who was found guilty in November, Christopher Jordan, capped a string of wins by prosecutors in spoofing cases targeting some of Wall Street’s biggest banks, including Bank of America Corp., Deutsche Bank AG and Morgan Stanley. Two former Deutsche Bank and two former Bank of America traders previously each received one-year sentences.
JPMorgan, the largest US bank, agreed in 2020 to pay $920 million to settle the Justice Department’s allegations against it — by far the biggest fine by any financial institution accused of market manipulation since the 2008 global financial crisis.
Prosecutors charged several members of the team Nowak led at JPMorgan. Three of them pleaded guilty and testified against Nowak and Smith. The witnesses described how Nowak and Smith routinely placed huge buy and sell orders they never intended to execute — part of their strategy to push prices in the direction that would profit the bank.
Christiaan Trunz, a former Smith protege and one of the traders who pleaded guilty and cooperated, told jurors that he learned to spoof by watching Nowak and Smith for years. When Trunz came under scrutiny for his own spoof trades, he said Nowak coached him to lie to compliance officials and later counseled him against pleading guilty as prosecutors were preparing criminal charges against top executives on the trading desk.
Trunz testified that Smith was so fast at placing and canceling bogus orders that his colleagues would joke that he needed to put ice on his fingers to cool them down.
“This was an open strategy on the desk,” said Trunz, who sat next to Smith and watched him click his computer mouse rapidly to place and cancel trades. “It wasn’t hidden.”
Spoofing was common in the commodity world, where traders would place a buy or sell offer they never intended to executive — hoping to manipulate prices in the direction they wanted to make a profit. The practice became illegal after passage of the 2010 Dodd-Frank Act, which included several banking and market reforms in the wake of the financial crisis.
At trial, Smith’s lawyer said his client’s orders were legitimate, and that there were other explanations to buy and sell precious metals contracts at the same time on behalf of customers.
The case is US v. Smith et al, 19-cr-00669, US District Court, Northern District of Illinois (Chicago).
https://finance.yahoo.com/news/ex-jpmorgan-gold-traders-prison-200420522.html
FDIC to Propose New Regulations for Midsize Lenders Next Week
US banking watchdogs will next week propose requiring that banks with as little as $100 billion in assets issue enough long-term debt to cover capital losses if they ever failed.
The plans to be released by the Federal Deposit Insurance Corp. on Aug. 29 are the latest response by Washington officials to the failure of three regional banks earlier this year. The FDIC said it will also unveil a plan to make lenders of that size bolster their hypothetical wind down plans.
The issue of who should shoulder costs for bank failures became contentious earlier this year after the US invoked a so-called systemic-risk exception to let the FDIC cover all deposits at Silicon Valley Bank and Signature Bank — including those that were unsecured. The move cost the government’s bedrock Deposit Insurance Fund, which is typically used to cover as much as $250,000 in an account, billions of dollars.
A buffer of long-term debt would help protect the fund by avoiding the need for a system-risk exception, FDIC Chairman Martin Gruenberg said on Aug. 14.
Gruenberg also recently said that improving the firms’ resolution plans, which are known as living wills, could reduce reliance on the FDIC to broker a sale if they ever fail. He has said the plan would require banks to identify parts that could be sold separately, letting a collapsed firm possibly tap into a broader range of potential buyers.
https://finance.yahoo.com/news/fdic-propose-regulations-midsize-lenders-215722867.html
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