Teva outlook cut

 

• Revenues of $3.6 billion

• GAAP diluted EPS of $0.05

• Non-GAAP diluted EPS of $0.59

• Cash flow generated from operating activities of $543 million

• Free cash flow of $685 million

• 2022 revenues outlook revised mainly due to continued foreign exchange headwinds; non-GAAP tax rate outlook range revised to 12% - 14%; operating income, Adjusted EBITDA, EPS and free cash flow reaffirmed:

• Revenues of $14.8 - $15.4 billion vs. previous range of $15.0 - $15.6 billion

• Adjusted EBITDA of $4.7 - $5.0 billion

• Non-GAAP diluted EPS of $2.40 - $2.60

• Free cash flow of $1.9 - $2.2 billion

• Non-GAAP tax rate of 12% - 14% vs. previous range of 13%-14%

• https://finance.yahoo.com/news/teva-reports-third-quarter-2022-110000361.html

Virax Biolabs Introduces RSV-Influenza-COVID Triple Virus Antigen Rapid Test Kit

Kits available in November for Distribution

Virax Biolabs ("Virax" or the "Company") (Nasdaq: VRAX), an innovative biotechnology company focused on the prevention, detection, and diagnosis of viral diseases, announced today the distribution of a RSV-Influenza-COVID Triple Virus Antigen Rapid Test Kit has been launched in markets accepting the CE mark, such as the European Union. The test kits are for use in both at-home and in point-of-care settings to accurately identify infections related to respiratory syncytial virus (RSV), influenza and COVID-19 with results typically available in 15 minutes. The specialized diagnostic kits can be found by contacting the company's sales representatives.

While lesser known to the general public than influenza and COVID-19, RSV can be a serious illness.  According to the European Health Management Association, RSV is the most common cause of hospitalization in infants and also causes a large number of hospitalizations among the elderly.  RSV infection can lead to pneumonia, congestive heart failure and severe symptoms in those with preexisting conditions involving the lungs.

https://finance.yahoo.com/news/virax-biolabs-introduces-rsv-influenza-113000992.html

Bausch Health trims guidance

 ausch Health updated its consolidated guidance for the full year 2022 as follows:

• Full year revenue range of $8.0 - $8.17 billion compared with prior guidance of $8.05 - $8.22 billion

• Full year revenues flat to up 2% on an organic basis (unchanged)

• Full year Adjusted EBITDA (non-GAAP)1 range of $2.99 - $3.09 billion compared with prior guidance of $3.02 - $3.12 billion

https://finance.yahoo.com/news/bausch-health-announces-third-quarter-110000416.html

Healing diabetic wounds by activating 'hidden' mechanism in the body

 Researchers at Indiana University School of Medicine are looking for ways to heal wounds by using a healing protein that is active in fetuses, but largely inactive in adults and absent in diabetic adults.

"We already know from previous studies at other institutions that if a fetus is wounded, it can regenerate the tissue, or repair it to be like new," said Chandan K. Sen, Ph.D., associate vice president of military and applied research, the J. Stanley Battersby chair and distinguished professor of surgery and director of the Indiana Center for Regenerative Medicine and Engineering at Indiana University School of Medicine.

"But after birth, such regenerative wound healing ability is lost. Healing in adults is relatively inefficient [and] often associated with undesirable scar formation."

In the study, published recently in Molecular Therapy, the team focused on a protein called nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase, or NPGPx. NPGPx is active in fetal tissue but becomes mostly inactive in the skin after birth.

"Nature essentially hides this fetal regenerative repair pathway in the adult body," Sen said. "We spotted its absence, and then activated it to improve healing of diabetic wounds."

Researchers used tissue nanotransfection technology developed by faculty at the ICRME to deliver the NPGPx gene to the wound site. Diabetic wounds, which are complicated skin injuries in people with diabetes, are particularly difficult to treat and often lead to amputations or other complications because of how easily they can become infected.

"This is an exciting new approach to harness fetal repair mechanisms to close diabetic wounds in adults," Sen said.

"The study results show that while NPGPx has been known to be abundant in the fetal skin, but not after birth, it can be reactivated in the skin after an injury. We look forward to continued study aiming to achieve a more complete regenerative repair by improving our understanding of how NPGPx functions."

More information: Subhadip Ghatak et al, Driving adult tissue repair via re-engagement of a pathway required for fetal healing, Molecular Therapy (2022). DOI: 10.1016/j.ymthe.2022.09.002

https://medicalxpress.com/news/2022-11-diabetic-wounds-hidden-mechanism-body.html

Treatment-resistant prostate cancer: Small trial shows 40% progression-free survival

 Investigators from Cedars-Sinai Cancer have identified an investigational therapeutic approach that could be effective against treatment-resistant prostate cancer. Results of their Phase II clinical trial, published in Molecular Therapy, have led to a larger, multicenter trial that will soon be underway.

Cancer of the prostate, a small gland just below the bladder, is the second-leading cause of cancer-related death in men. Many prostate tumors are not aggressive and may require no or minimal treatment. Aggressive tumors are initially treated with surgery or radiation therapy.

In about one-third of patients, the cancer comes back after initial treatment, said Neil Bhowmick, Ph.D., research scientist at Cedars-Sinai Cancer, professor of Medicine and Biomedical Sciences and senior author of the study. Those patients are usually treated with medications that suppress the actions of testosterone and other androgens—male hormones that help prostate tumors grow.

"Patients do really well until the tumor figures a way around the androgen-suppressing therapy," Bhowmick said. "One way that it can do this is to cause cells to make only part of the protein that the drug binds to, rendering the drug useless. The partial proteins are called splice variants."

Through research with human cells and laboratory mice, study first author Bethany Smith, Ph.D., a project scientist in the Bhowmick Lab, figured out that the cancer cells were signaling to the surrounding supportive cells through a protein called CD105 to make these slice variant proteins. Investigators then conducted a trial in human patients to test a drug that they hoped would keep those partial proteins from forming by inhibiting CD105.

In the trial, nine patients whose tumors were resistant to androgen-blocking therapy continued that therapy but were also given a CD105 inhibitor called carotuximab. Forty percent of those patients experienced progression-free survival, based on radiographic imaging.

"Every single one of the patients in our trial was totally resistant to at least one androgen suppressor, and the normal course of action would be to simply try a different one or chemotherapy, which research has shown generally doesn't stop tumor growth for more than about three months," Bhowmick said. "Carotuximab prevented the cancer's workaround and made the tumor sensitive to androgen-suppressing therapy."

Importantly, Bhowmick said, carotuximab also appears to prevent androgen receptor splice variants in the supporting cells surrounding tumors, further sensitizing the tumor to the androgen suppressor.

"We found that this therapy may be able to, especially in early cancers, resensitize select patients to androgen suppression. This could allow patients to avoid or delay more toxic interventions such as cytotoxic chemotherapy," said Edwin Posadas, MD, co-director of the Experimental Therapeutics Program, medical director of the Urologic Oncology Program/Center for Uro-Oncology Research Excellence (CURE), associate professor of Medicine at Cedars-Sinai and a co-author of the study.

"We also hope to find ways of predicting which patients are most likely to benefit from this approach by testing blood and tissue samples using next-generation technologies housed at Cedars-Sinai Cancer."

Study co-author Sungyong You, Ph.D., director of the Urologic Oncology Bioinformatics Group, pinpointed three biomarkers that could help indicate which patients will respond to this investigational therapy, and the team will validate those markers in a new clinical trial. This will allow future studies to target patients most likely to be helped by this intervention, Bhowmick said.

More information: Bethany N. Smith et al, Antagonizing CD105 and androgen receptor to target stromal-epithelial interactions for clinical benefit, Molecular Therapy (2022). DOI: 10.1016/j.ymthe.2022.08.019

https://medicalxpress.com/news/2022-11-therapies-treatment-resistant-prostate-cancer-small.html

Testing 2 Alzheimer's drugs head-to-head in first-ever virtual clinical trial

 An estimated 6.2 million Americans ages 65 and older are living with Alzheimer's disease. The national Alzheimer's Association predicts that number to grow to 13.8 million by 2060, barring the development of medical breakthroughs that would prevent, slow or cure the debilitating disease.

Scientists may be one step closer to such a breakthrough thanks to a first-of-its-kind computer model that has successfully simulated a clinical trial evaluating the efficacy of multiple treatments for Alzheimer's disease (AD).

"We're calling this a virtual clinical trial, because we used real, de-identified patient data to simulate health outcomes," said Wenrui Hao, associate professor of mathematics at Penn State, who is lead author and principal investigator on the study published in the September issue of the journal PLoS Computational Biology.

"What we found aligns almost exactly with findings in prior clinical trials, but because we were using a virtual simulation, we had the added benefit of directly comparing the efficacy of different drugs over longer trial periods."

Using clinical and biomarker data, the researchers built a computational causal model to run virtual trials on the FDA-approved treatment aducanumab, as well as another promising therapy under evaluation, donanemab. The two drugs are some of the first treatments designed to work directly on what may cause the disease, instead of just treating the symptoms.

The researchers set the trial timeframe for both medium-term (78 weeks) and long-term (10 years) periods with low-dose (6 mg/kg) and high-dose (10 mg/kg) regimens for aducanumab, and a single-dose regimen (1400 mg) for donanemab. These are the same doses used in the human trials for FDA-approval.

Their results confirmed what was found in actual clinical trials. Both drugs had a large and sustained effect on removing beta-amyloid plaques, a peptide found in the brains of people with Alzheimer's disease. The team also found both treatments had a small effect on slowing cognitive decline in patients, though donanemab was slightly more effective than aducanumab over a simulated 10-year period.

"With over 10 anti-amyloid therapies in development, an important question is which one is better," said collaborator and co-principal investigator on the study, Dr. Jeffrey Petrella, Professor of Radiology and Director of the Alzheimer Imaging Research Laboratory at Duke University. "It often takes tens of millions of dollars and many years to do a head-to-head comparison of drugs. Our study showed that the effect of these two anti-amyloid drugs on slowing cognitive decline is actually quite modest—and if given late in life, barely detectable."

Petrella explained that questions remain within the medical community regarding the efficacy of removing amyloid plaques and whether or not the treatment, which is delivered intravenously on a monthly basis, actually prevents or delays cognitive decline.

"This uncertainty, combined with the 99% failure rate of trials of other classes of AD treatments, is rooted in an incomplete understanding of the complex mechanisms resulting in AD, and how disease trajectory and response to treatment may vary individual-to-individual," the researchers write. "It is likely, therefore, that personalized treatment will need to play a central role in the future management and counseling of patients with AD."

The researchers also used their model to develop personalized treatment plans for individual virtual patients, taking into account the potential side effects of anti-amyloid therapy such as brain swelling and bleeding, headaches, dizziness, nausea, confusion and vision problems. The team's results show that the optimal treatment regimen gradually increases the dose until it reaches a maximum dosage and continues at a steady state.

"Our objective was to minimize cognitive decline while also minimizing the treatment dosage to limit the corresponding side effects," said Suzanne Lenhart, Chancellor's Professor of Mathematics at the University of Tennessee, Knoxville, who collaborated on the study. "Our model will give the optimal treatment level over time of the drug, but maybe even more importantly, it provides the optimal personalized treatment plan for each patient."

Using the framework they developed, the researchers will now look to apply optimal treatment computational modeling to other single and combination AD therapies that are currently under evaluation and incorporate new clinical trial data into their model as it becomes available.

The researchers acknowledged that such virtual trials incorporate numerous evidence-based assumptions regarding disease pathogenesis, therapeutic mechanism, side effects and a host of other factors which could impact outcome.

"Despite these limitations, this is the first step towards tailored clinical trials," Petrella said. "We've shown that this type of model can work. I envision it being used as a precision tool to enhance actual clinical trials, optimizing dosages and combinations of drugs for individual patients."

More information: Wenrui Hao et al, Optimal anti-amyloid-beta therapy for Alzheimer's disease via a personalized mathematical model, PLOS Computational Biology (2022). DOI: 10.1371/journal.pcbi.1010481

https://medicalxpress.com/news/2022-11-scientists-alzheimer-drugs-head-to-head-first-ever.html

Common dietary fiber promotes allergy-like immune responses in preclinical studies

 A type of dietary fiber called inulin, commonly used in health supplements and known to have certain anti-inflammatory properties, can also promote an allergy-related type of inflammation in the lung and gut, and other parts of the body, according to a preclinical study from researchers in the Friedman Center for Nutrition and Inflammation and Jill Roberts Institute for Inflammatory Bowel Disease at Weill Cornell Medicine and in the Boyce Thompson Institute on Cornell's Ithaca campus.

The study, published Nov. 2 in Nature, found that dietary inulin fiber alters the metabolism of certain gut bacteria, which in turn triggers what scientists call type 2 inflammation in the gut and lungs. This type of inflammation is thought to have evolved in mammals chiefly to defend against parasitic worm ("helminth") infections, and is also part of normal wound healing, although its inappropriate activation underlies allergies, asthma and other inflammatory diseases.

"There's a lot to think about here, but in general, these findings broaden our understanding of the relationship between diet, immunity, and the normally beneficial microorganisms that constitute our microbiota and colonize our bodies," said study co-senior author Dr. David Artis, director of the Friedman Center for Nutrition and Inflammation and the Michael Kors Professor of Immunology at Weill Cornell Medicine.

The study's scientific participants reflect the Friedman Center's highly cross-collaborative research mission, drawing on expertise in bacterial genetics, biochemistry and immunology at Weill Cornell Medicine in New York City and Cornell's Ithaca campus. Dr. Chun-Jun Guo, assistant professor of immunology in medicine at Weill Cornell Medicine, and Dr. Frank Schroeder, professor at the Boyce Thompson Institute and in the Department of Chemistry and Chemical Biology in the College of Arts and Sciences on Cornell's Ithaca campus, teamed up with the Artis laboratory to gain a detailed understanding of how an important dietary component affects the microbiome and the immune response. The study's first author is Dr. Mohammad Arifuzzaman, a postdoctoral researcher in the Artis laboratory. Dr. Artis is also director of the Jill Roberts Institute for Inflammatory Bowel Disease at Weill Cornell Medicine.

Small amounts of inulin are present in a wide variety of fruits and vegetables, including bananas, asparagus, and garlic. Inulin is also frequently concentrated in commonly available high-fiber dietary supplements. Previous studies have found that inulin boosts populations of beneficial gut bacterial species, which in turn boost levels of anti-inflammatory immune cells called regulatory T (Treg) cells.

In this new study, the researchers examined inulin's effects more comprehensively. They gave mice an inulin-based, high-fiber diet for two weeks, and then analyzed the many differences between these mice and mice that had been fed a diet lacking inulin. A major difference was that the inulin diet, while increasing Treg cells, also induced markedly higher levels of white blood cells called eosinophils in the gut and lungs. A high level of eosinophils is a classic sign of type 2 inflammation and is typically seen in the setting of seasonal allergies and asthma.

Ultimately the researchers found that the eosinophil response was mediated by immune cells called group 2 innate lymphoid cells (ILC2s), which were activated by elevated levels of small molecules called bile acids in the blood. The bile acid levels were elevated due to the inulin-induced growth of certain bacterial species—a group called Bacteroidetes, found in both mice and humans—which have a bile acid-metabolizing enzyme.

"We were amazed to find such a strong association between inulin supplementation and increased bile acid levels," Dr. Schroeder said. "We then found that deletion of the bile acid receptor abrogates the inulin-induced inflammation, suggesting that microbiota-driven changes in bile acid metabolism underlie the effects of inulin."

"When we colonized germ-free mice (mice without microbiota) with one of these bacterial species, and then knocked out the gene for one bacterial enzyme that promotes bile acid production, the whole pathway leading from inulin to eosinophilia and allergic inflammation was blocked," Dr. Guo said.

The finding that inulin promotes type 2 inflammation does not mean that this type of fiber is always "bad," the researchers said. They found that inulin did worsen allergen-induced type 2 airway inflammation in mice. But the experiments also confirmed inulin's previously reported effect at boosting anti-inflammatory Treg cells, which may in many cases, outweigh some pro-inflammatory impact. Moreover, a type 2 immune response, which in the gut and lungs involves an increased production of tissue-protecting mucus, is not necessarily harmful in healthy people—indeed, the researchers found in their mouse experiments that the inulin-induced type 2 inflammation enhances the defense against helminth infection.

"It could be that this inulin to type-2-inflammation pathway represents an adaptive, beneficial response to endemic helminth parasite infection, though its effects in a more industrialized, helminth-free environment are more complex and harder to predict," said Dr. Arifuzzaman.

The researchers now plan to use their multi-disciplinary, multi-platform approach to study systematically the immune effects of the different types of dietary fiber as well as a range of other dietary supplements in different states of health and disease.

More information: Mohammad Arifuzzaman et al, Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation, Nature (2022). DOI: 10.1038/s41586-022-05380-y

https://medicalxpress.com/news/2022-11-common-dietary-fiber-allergy-like-immune.html