Veru Publishes Phase 3 Study of Sabizabulin for Hospitalized COVID Patients at High Risk for Respiratory Distress

 Veru Inc. (NASDAQ: VERU), a biopharmaceutical company focused on developing novel medicines for COVID-19 and other viral and ARDS-related diseases and for the management of breast and prostate cancers, today announced that the Phase 3 COVID-19 study results of Sabizabulin for the Treatment of Hospitalized COVID-19 Patients at High Risk for Acute Respiratory Distress Syndrome (ARDS) were presented at the 11^th International Conference on Emerging Infectious Diseases (ICEID) on August 8, 2022.

Presentation Highlights

• Sabizabulin is an oral, novel microtubule disruptor that has dual antiviral and anti-inflammatory activity.
• In a double-blind, multicenter, and placebo-controlled Phase 3 clinical study evaluating sabizabulin 9 mg versus placebo (randomized 2:1) in 204 hospitalized moderate-severe COVID-19 patients (requiring oxygen) who were at high risk for ARDS and death (NCT04842747). At a planned interim analysis in the first 150 patients randomized, the study was halted by the Independent Data Monitoring Committee for clear demonstration of efficacy. For the primary endpoint which was all cause mortality by Day 60, a clinically meaningful and statistically significant 55.2% relative reduction in deaths was observed in the intent-to-treat population (p=0.0041). Sabizabulin treatment also resulted in a 43% relative reduction in days in ICU (p=0.0013), 49% relative reduction in days on mechanical ventilation (p=0.0013), and 26% relative reduction in days in hospital (p=0.0277) vs placebo. The proportion of patients with an adverse event or a serious adverse event was lower in the sabizabulin compared to the placebo group.

August 08, 2022: 4:15 PM – 4:30 PM Eastern Time
Oral Sabizabulin Reduces Mortality in Hospitalized COVID-19 Patients with at High Risk for ARDS
Oral Presentation Number: E4.5
Presenter: Michael Gordon MD, Chief Medical Officer at HonorHealth Research and Innovation Institute in Scottsdale, Arizona

Additional information on the meeting can be found on the ICEID website: https://www.iceid.org/

https://www.biospace.com/article/releases/veru-announces-presentation-of-phase-3-study-of-sabizabulin-for-the-treatment-of-hospitalized-covid-19-patients-at-high-risk-for-acute-respiratory-distress-syndrome/

Merck Returns to Alzheimer’s Disease with $1.1B Cerevance Pact

 With an investment valued at up to $1.1 billion, Merck is diving back into Alzheimer’s research through a collaboration with Cerevance. Using Cerevance’s proprietary Nuclear Enriched Transcript Sort sequencing (NETSseq) technology platform, the two companies have partnered to identify new targets for the treatment of Alzheimer’s disease (AD).

On Tuesday morning, the two companies announced the collaboration, which includes the out-licensing of one discovery-stage program to Merck. For privately-held Cerevance, the partnership comes months after the company posted positive mid-stage data in another neurological disease space, Parkinson’s. That study, which assessed the oral compound CVN424, showed that treatment with the drug developed through the NETSseq platform was able to reduce the “OFF” times for Parkinson’s patients. “OFF” refers to the occasions when Parkinson’s patients experience disease symptoms despite being on medication. 

CVN424 was developed to target GPR6, a G-coupled protein receptor. That receptor was targeted after the NETSseq platform determined it was highly expressed in striatal medium spiny neurons in the indirect pathway of the basal ganglia circuit. The technology platform is capable of profiling neuronal and glial cell populations at unprecedented depths. It’s that deep analysis that Merck is banking on to find a new treatment option for Alzheimer’s, particularly following the setbacks of the amyloid-beta approaches to treating the disease.

Craig Thompson, chief executive officer of Cerevance, said the collaboration with Merck is continued validation of the company’s proprietary NETSseq technology. In an interview with BioSpace, Thompson, who was appointed to the role of CEO earlier this year, said Cerevance began discussing potential collaborations in the CNS space following the release of the positive Phase II Parkinson’s data. Merck was one of the companies that expressed significant interest in the data generated by NETSseq and its potential in Alzheimer’s disease, which has repeatedly proven to be a complex disease to target with therapeutics.

Merck Takes Another Shot at Alzheimer's

For Merck, delving back into Alzheimer’s comes several years after the pharma giant experienced setbacks with experimental β-site amyloid-precursor-protein-cleaving enzyme (BACE) inhibitors. In 2018, the company’s BACE inhibitor verubecestat failed in a Phase III Alzheimer’s trial. An external Data Monitoring Committee halted that study of patients with prodromal Alzheimer’s disease early after an interim safety analysis. 

One year prior, a Phase II/III study of verubecestat in mild-to-moderate Alzheimer’s disease was also halted following the recommendation of an external data monitoring committee that said there was “virtually no chance of finding a positive clinical effect.”

Thompson, who worked at Merck for 12 years earlier in his career, said he was thrilled the pharma giant was interested in working with Cerevance, mainly because he is highly familiar with the “scientific rigor” the larger company employs in its development programs.

“It gave me a lot of joy that they found the NETSseq program,” he said.

Cerevance's Novel NETSseq Platform

Over the next three years, the two companies aim to discover potential new targets for therapeutic approaches through the NETSseq platform, which was developed at Rockefeller University.

The NETSseq program enabled researchers to comprehensively profile-specific brain cell types, including both neurons and glial cells. Using the program, Cerevance has been able to isolate specific cell populations in brain tissue samples, revealing biological pathways that underlie neurodegenerative and psychiatric diseases that have proven to be difficult to see in animal models or differentiated human stem cells, Thompson said. The technology platform will allow Merck and Cerevance to take a “fresh approach” to Alzheimer’s. They hope the collaboration will reveal novel therapeutic targets that can slow or inhibit disease progression. 

Jason M. Uslaner, vice president and head of neuroscience discovery at Merck Research Laboratories, said progress in the understanding of the biology of neurodegenerative diseases has revealed new mechanisms for potential therapeutic intervention. 

“We look forward to advancing the discovery program as well as taking advantage of the NETSseq platform to identify new targets with the team at Cerevance,” Uslaner said in a statement. 

Under the terms of the deal, Merck provided Cerevance with $25 million upfront, including the in-licensing of the early-development asset. Cerevance will be eligible for development and commercial milestone payments that total approximately $1.1 billion. Should any product from the collaboration become commercialized, Cerevance will also be eligible for potential royalties on sales.

Merck isn’t the only big pharma company to partner with Cerevance. Three years ago, Cerevance and Japanese pharma powerhouse Takeda partnered on a collaboration to tackle gastrointestinal disorders that have their roots in the central nervous system. It is believed that some cell types found in the brain can impact the development of GI diseases.

https://www.biospace.com/article/merck-returns-to-alzheimer-s-disease-with-1-1-billion-cerevance-pact/

Biden struggles with coughing fits during speech days after COVID recovery

 President Biden had to repeatedly halt remarks on the White House lawn due to a persistent hacking cough Tuesday — just days after he tested negative for COVID-19 following a “rebound” infection.

Biden, 79, paused several times during his remarks on passage of a $280 billion computer-chip bill, including at one point to sip water.

“Excuse me, I’m sorry,” the president said, adding, “I’m going to take another sip of water.”

The uncomfortable extended fit was notably more severe than Biden’s standard throat-clearing during remarks, which his physician Dr. Kevin O’Connor last year attributed to gastroesophageal reflux.

After completing his speech, Biden was seen blowing his nose before members of Congress crowded around to watch him sign the technology legislation. He did not wash his hands before greeting Senate Majority Leader Chuck Schumer (D-NY) and he proceeded to mingle with other legislators present.

Biden was also spotted coughing Monday during a briefing on storm damage in eastern Kentucky, but the hacking was more pronounced Tuesday.

“This is the most difficulty [Biden] has had getting through prepared remarks in a while as he struggles with repeated coughing/throat clearing,” tweeted Voice of America journalist Steve Herman.

The uncomfortable extended fit was notably more severe than Biden’s standard throat-clearing during remarks.

MANDEL NGAN/AFP via Getty Images

President Biden had to repeatedly halt remarks on the White House lawn due to a persistent hacking cough.

Reuters

The White House has refused to allow Dr. O’Connor to directly take reporter questions on Biden’s recent experience with COVID-19.

REUTERS/Evelyn Hockstein

Jake Schneider, deputy director of rapid response at the Republican National Committee, tweeted, “Just imagine a scenario in which Donald Trump gives a speech days after he gets COVID and hacks nasty coughs into his hands every 30 seconds. It’d be a national emergency. That’s exactly what Joe Biden is doing this morning. Predictably, crickets.”

The White House has refused to allow Dr. O’Connor to directly take reporter questions on Biden’s recent experience with COVID-19. The lack of transparency drew objections from prominent veteran journalists who said that the lack of Q&A is a deviation from historical practice during a serious presidential illness.

Biden tested negative for COVID-19 on both Tuesday and Monday, the White House said. 

The existence of lingering symptoms from the virus — or “long COVID” — is more common among older people, with roughly one in four patients over age 65 experiencing longer-term symptoms, according to a May study from the Centers for Disease Control and Prevention.

The American Lung Association says, however, that a lingering cough isn’t necessarily cause for alarm.

“The most common symptom that signifies healing is a lingering cough because coughing is your lung’s way of sweeping out dead cells,” the Lung Association says on an informational page. “In the case of COVID-19, this cough could last for as long as six months after the viral infection, especially if the patient contracted Omicron because it is more airway dependent than the original strain.”

https://nypost.com/2022/08/09/biden-struggles-with-coughing-fit-during-speech-days-after-covid-recovery/

China closes Potala Palace after COVID-19 reported in Tibet

 Chinese authorities have closed Tibet’s famed Potala Palace after a minor outbreak of COVID-19 was reported in the Himalayan region.

The response underscores China’s continued adherence to its “zero-COVID” policy, mandating lockdowns, routine testing, quarantines and travel restrictions, even while most other countries have reopened.

A notice on the palace’s Weixin social media site said the palace that was the traditional home of Tibet’s Buddhist leaders would be closed from Tuesday, with a reopening date to be announced later.

Tibet’s economy is heavily dependent on tourism and the Potala is a key draw.

China says its hard-line policy has been successful in preventing large-scale hospitalizations and deaths, while critics including the World Health Organization have decried its impact on the economy and society and said it is out of step with the changing nature of the virus and new methods of prevention and treatment.

China announced 828 new cases of domestic transmission on Tuesday, 22 of them in Tibet. The majority of those cases showed no symptoms.

Elsewhere in China, authorities sent a first planeload of 125 tourists out of the beach resort of Sanya, where tens of thousands of travelers have been stuck since Saturday by a COVID-19 lockdown.

State broadcaster CCTV said the city in Hainan province was organizing more flights to return tourists home in batches after the initial flight to Xi’an. They are allowed to leave only after multiple negative virus test results.

The provincial capital, Haikou, will be locked down for 17 hours on Wednesday from 6 a.m. to 11 p.m., the city announced.

https://apnews.com/article/covid-health-travel-china-73df01990265a237b074233f1be1bca1

Young Adults With NSCLC More Apt to Get Advanced Disease Diagnosis

 Younger adults (ages under 50) with non-small cell lung cancer (NSCLC) were significantly more likely than older adults to be diagnosed with advanced disease, a researcher said here.

In 2018, 5 years after the U.S. Preventive Services Task Force recommended low-dose CT lung cancer screening (LCS) for people over age 55 -- lowered to age over 50 in 2021 -- with certain risk factors, 64% of patients ages 20-49 with NSCLC were diagnosed with stage IV disease versus 43% ages 50-79, for an absolute difference of 21%, reported Chi-Fu Jeffrey Yang, MD, of Massachusetts General Hospital in Boston.

That absolute difference was substantially greater than the 13% difference observed in 2010, when 60% of younger patients were diagnosed with stage IV disease versus 47% of older patients, he said in a presentation at the World Conference on Lung Cancer (WCLC).

"Different tumor biology, delays in diagnosis, and the absence of methods to facilitate early detection of lung cancer among young adults likely contributes to the high rate of stage IV disease diagnosed in this population," said Yang at a WCLC press briefing.

However, WCLC discussant Anand Devaraj, MD, of Royal Brompton Hospital, Imperial College in London, cautioned that "it's not possible to determine whether this stage shift is directly attributable to screening -- there may be other factors involved."

In 2021, the task force revised its LCS recommendation for those ages 50-80 who have a 20 pack-year smoking history and currently smoke, or those that have quit within the past 15 years. The recommendation also states that "Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery."

"What this data [from Yang's group] prompted me to think about is the challenge we all face ... which is how to identify high-risk participants in groups that cannot be easily accessed, and that is not just younger patients, but also older patients without sufficient risk factors based on current risk models," Devaraj said.

Yang and colleagues used the Surveillance Epidemiology End Results (SEER) database and the National Cancer Database to identify patients, ages 20-79, diagnosed with NSCLC from 2010-2018. During that period 1,038, 5,682, and 39,323 individuals ages 20-29, 30-39, and 40-49, respectively, were diagnosed with NSCLC.

The authors observed that with increasing age, the percentage of patients diagnosed with stage I NSCLC rose over time, while the percentage of patients diagnosed with stage IV cancer decreased. Specifically, they found that among younger adults, 8% of patients (ages 20-29) were diagnosed with stage I disease, while 76% were diagnosed with stage IV disease. The percentage of patients in the 30-39 and 40-49 age groups diagnosed with stage I disease slightly increased to 10% and 14%, respectively, while the percentage of patients diagnosed with stage IV disease in those age groups declined, but was still high at 70% and 60%, respectively.

In contrast, 29% of patients (ages 70-79) were diagnosed with stage I disease and 40% were diagnosed with stage IV disease.

Yang and his colleagues also looked at survival data and found that while there was no improvement in early diagnosis among young adults, median overall survival (OS) of young adults diagnosed with NSCLC did increase by 14 months from 2010-2018, largely due to improvements in survival for patients with advanced disease.

"Notably, these improvements in median overall survival appear to align with the NCCN [National Comprehensive Cancer Network] recommendation for genetic testing for EGFR and ALK mutations in 2012, as well as the FDA's of immunotherapies in 2015," Yang said.

However, Yang and colleagues found that the youngest patients (ages 20-29) diagnosed with NSCLC had the lowest 5-year survival rates at 20% versus 5-year OS rates ranging from 24% for older patients (ages 70-79) to 28% for middle-age patients (40-49). Moreover, 5-year OS for patients diagnosed with stage IV disease was particularly low in all younger age groups (11%, 15%, and 10% for patients in the 20-29, 30-39, and 40-49 age groups, respectively).

Study limitations included that fact that it did not include data regarding disease-free or recurrence-free survival, tumor biomarkers, the use of targeted therapy, or the time from initiation presentation to lung cancer diagnosis.

Yang noted that "these improvements in median survival observed in young adults diagnosed with lung cancer are encouraging," but his group stressed that strategies to increase the early detection of lung cancer among younger patients, who are generally ineligible for LCS, are "urgently needed."

Disclosures

Yang disclosed no relationships with industry.

Primary Source

International Association for the Study of Lung Cancer

Source Reference: Potter A, et al "Early diagnosis of lung cancer among younger vs. older adults: Widening disparities in the era of lung cancer screening" WCLC 2022; Abstract 2518.

https://www.medpagetoday.com/meetingcoverage/iaslc/100104

AstraZeneca Reports Promising Data From Lung Cancer Trial

 AstraZeneca PLC said Tuesday that initial results from a trial of datopotamab deruxtecan-based combinations show promising clinical activity in patients with advanced non-small-cell lung cancer.

The pharmaceutical giant said that the trial showed encouraging efficacy and safety results that justify further studies.

Datopotamab deruxtecan is being jointly developed by AstraZeneca and Daiichi Sankyo.

"We look forward to continuing this important research with the goal of providing a new, effective treatment option for patients with advanced non-small-cell lung cancer," Astra's Chief Medical Officer and Oncology Chief Development Officer Cristian Massacesi said.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-Reports-Promising-Data-From-Lung-Cancer-Trial-41250580/

Cyteir pauses development of cancer med, funnels cash towards lead asset

 Cyteir is pressing pause on its next-in-line cancer med in a bid to extend its cash runway by six months and make sure it can pay for clinical work on its lead asset.

The company says that it will halt the development of CYT-1853 and pump the breaks on asking regulators to greenlight its clinical ambitions, according to the company’s latest earnings released Tuesday. The expectation is that the move will elongate Cyteir’s cash runway from the beginning of 2024 to mid-year. The extra money will go towards funding the company’s lead oncology med CYT-0851 and “discovery research efforts to expand the company’s synthetically lethal preclinical pipeline.” 

CYT-1853 is designed to inhibit monocarboxylate transporters, a type of protein involved with cancer metabolism. By year's end, Cyteir had hoped to ask regulators to launch CYT-1853 into the clinic. But amid a dismal—albeit slightly improving—biotech market, preserving cash reserves is paramount. 

Instead, at the top of the company’s agenda is clearing the clinical pathway for CYT-0851, currently in two phase 1 trials as a monotherapy and combo therapy respectively to treat solid tumors and hematologic malignancies. Initial data of the monotherapy in solid tumors is expected in the fourth quarter while data in hematologic malignancies is slated for the first half of 2023. 

Additionally, Cyteir has opened a phase 2 cohort testing the monotherapy in breast cancer patients, replacing the company’s multiple myeloma arm, which has been discontinued. The company chalked the move up to the “evolving treatment landscapes” in multiple myeloma and large B-cell lymphoma, hinting that it wouldn’t be able to compete against other companies in the space. 

After raising $29 million in early 2018, Cyteir joined the public biotech boom just as it was beginning to slide, closing a $133.2 million IPO in June 2021. Since then, the company’s shares have crumbled, from $17.40 to $2.52. As for the company’s existing runway, it currently has $166.4 million on hand. After reporting $4.5 million more in R&D spend in the first quarter of 2022 compared to the year before, development costs have evened out and are now about the same as the second quarter of last year. 

https://www.fiercebiotech.com/biotech/cytier-pauses-development-deck-cancer-med-funnels-cash-towards-lead-asset