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Thursday, December 2, 2021

Humanigen: Peer-Reviewed Paper, Independent Expert Commentary on Positive Phase 3 Lenzilumab Results

 

  • Lenzilumab is a variant-agnostic therapeutic that targets the dysregulated host immune response, an approach which may be of greater value than targeting the virus in hospitalized patients1

  • Per the paper, the implication from all the available evidence is that "Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19 who were treated concurrently with other available therapies"2

  • Results of the LIVE-AIR Phase 3 trial demonstrate treatment of hospitalized COVID-19 patients with lenzilumab results in a statistically significant 54% relative improvement in the likelihood of survival without the need for invasive mechanical ventilation ("SWOV")

Glaxo: Tests indicate antibody drug works against Omicron

 Laboratory analysis of the antibody-based COVID-19 therapy GlaxoSmithKline (GSK) is developing with U.S. partner Vir has indicated the drug is effective against the new Omicron variant, the British drugmaker said on Thursday.

A GSK statement said that lab tests and a study on hamsters have demonstrated the sotrovimab antibody cocktail to work against viruses that were bio-engineered to carry a number of hallmark mutations of the Omicron variant.

The tests are continuing to confirm the results against all of the Omicron mutations, with an update expected by the end of the year, it added.

The antibody is designed to latch on to the spike protein on the surface of the coronavirus, but Omicron has been found to have an unusually high amount of mutations on that protein.

“Sotrovimab was deliberately designed with a mutating virus in mind," said Vir Chief Executive George Scangos, adding that the drug was targeting a region of the spike protein that was highly unlikely to mutate.

Separately, Britain's drug regulator on Thursday approved sotrovimab, also known under the brand name Xevudy, for people with mild to moderate COVID-19 and who are at high risk of developing severe disease.

The Medicines and Healthcare products Regulatory Agency (MHRA) recommended use of Xevudy as soon as possible and within five days of the onset of symptoms.

Sotrovimab is based on monoclonal antibodies, which are lab-made versions of the natural antibodies the body generates to fight off an infection. Similar products are offered or being developed by Eli Lilly, Regeneron and AstraZeneca.

Regeneron on Tuesday said that lab tests and computer modelling suggest that COVID-19 antibody drugs including Regeneron's would have reduced efficacy against the Omicron variant.

https://finance.yahoo.com/news/1-gsk-says-tests-show-075620812.html

Novartis expects new drugs to boost sales by at least 4% until 2026

 Novartis is confident of delivering annual revenue growth of 4% or higher until 2026, as it banks on multi-billion dollar sales of experimental and approved drugs including arthritis and psoriasis medicine Cosentyx.

Sales from these new products is expected to exceed and make up for a $9 billion hit from launches of copycat versions of its products in this period, the Swiss drugmaker on Thursday said in a presentation https://www.novartis.com/sites/novartis_com/files/novartis-r-d-day-2021.pdf ahead of an investor briefing.

The update comes weeks after Novartis said it would sell its stake in Roche to simplify its structure and focus on key offerings against diseases such as arthritis and cancer, following the launch of a review of its generic-drug unit Sandoz.

Novartis also expects core margins in innovative medicines to reach the high 30s by 2026, adding it had up to 20 assets in its pipeline that had blockbuster potential - meaning they could eventually yield annual sales of at least $1 billion.

The company said it was committed to maintain a strong and growing dividend in Swiss francs.

https://finance.yahoo.com/news/novartis-sees-annual-sales-growth-062924374.html

Dyne Submits IND Application to Initiate Trial for Duchenne Therapy

 - DYNE-251, Dyne’s First DMD Program, is Being Developed for Patients with Mutations Amenable to Skipping Exon 51 -

- DYNE-101 IND Submission in DM1 Expected in the First Quarter of 2022 -

- Initiation of Patient Dosing of DYNE-251 and DYNE-101 in Multiple Ascending Dose Clinical Trials Anticipated by Mid-2022 -

https://finance.yahoo.com/news/dyne-therapeutics-announces-submission-ind-133000648.html

Omeros to Sell OMIDRIA® Franchise for >$1B

 - Transaction to Lock in Ongoing Revenue Stream for Omeros and Focus the Company on its Complement Franchise of MASP-2 and MASP-3 Inhibitors –

-- Conference call today at 8:30 a.m. ET, 5:30 a.m. PT --

  • $125 million upfront payment and $200 million on achievement of commercial milestone

  • Royalties of 50% on U.S. net sales until the earlier of either January 1, 2025 or payment of the $200-million milestone, after which royalties adjust to 30% of U.S. net sales

  • Royalties of 15% on ex-U.S. net sales

  • OMIDRIA to become a premier product in Rayner’s ophthalmology franchise

  • In addition to acquiring the OMIDRIA commercial organization, including the current OMIDRIA sales force, Rayner plans to further expand its U.S. and ex-U.S. sales forces

  • Conference Call Details

    Omeros’ management will host a conference call to discuss today’s announcement. The call will be held today at 8:30 a.m. Eastern Time; 5:30 a.m. Pacific Time. To access the live conference call via phone, please dial (844) 831-4029 from the United States and Canada or (920) 663-6278 internationally. The participant passcode is 9080996. A telephone replay will be available for one week following the call and may be accessed by dialing (855) 859-2056 from the United States and Canada or (404) 537-3406 internationally. The replay passcode is 9080996.

    To access the live or subsequently archived webcast of the conference call on the internet, go to the company’s website at https://investor.omeros.com/upcoming-events.


Wednesday, December 1, 2021

Brazil sees 2 confirmed omicron cases, Latin America's 1st

 Health officials in Brazil have reported the country's first confirmed cases of the omicron variant in two travelers arriving from South Africa, the first such cases in Latin America

The Sao Paulo state health secretariat said a 41-year-old man and a 37-year-old woman are in isolation. The two had their tests taken on Nov. 25 and showed light symptoms of the disease at the time.

The secretariat statement said both travelers arrived in Brazil on Nov. 23 and took a PCR test before a trip scheduled for two days later. Their positive test results were collected at the Guarulhos international airport, outside Sao Paulo, before a return flight to South Africa.

"After the positive result, the couple was instructed to remain in isolation at home. Both are being monitored by state and municipal (authorities), as well as their respective family members," said the Sao Paulo health secretariat, which added that neither of the two are registered in the state's vaccination platform.

"An initial investigation did not identify them being vaccinated anywhere else," it said.

Sao Paulo city hall's health secretariat said the couple lives in South Africa and was visiting Brazil. It did not disclose their nationalities.

Another potential case of omicron has been under investigation by Brazilian authorities since Sunday.

The two Brazilians are the first confirmed cases in Latin America, which has suffered heavily from the coronavirus pandemic. Brazil alone has reported more than 600,000 deaths, a figure that analysts believe to be undercounted.

Brazil does not require COVID-19 vaccination from foreign travelers entering the country.

Earlier on Tuesday, Japan and France reported their first cases of the omicron variant, while new findings indicate the mutant coronavirus was already in Europe close to a week before South Africa sounded the alarm. It was last Wednesday, Nov. 24, that South African authorities reported the existence of the highly mutated virus to the World Health Organization.

Much remains unknown about the new variant, including whether it is more contagious, as some health authorities suspect, whether it makes people more seriously ill, and whether it can thwart the vaccine.

Brazil's health agency Anvisa said the entry took place before Sunday's federal government decision to block passengers arriving from South Africa. The South American country has blocked flights originating from or with stop overs in South Africa, Botswana, Eswatini, Lesotho, Namibia and Zimbabwe.

Sao Paulo Gov. João Doria said the state's COVID-19 scientific committee will reassess the end of the mask mandates, which was expected to come into force on Dec.11.

"We need to know the impact of this new variant" before deciding if removing masks is allowed outdoors, said Doria, who is also a presidential hopeful for next year's elections.

President Jair Bolsonaro, who has flouted health protocols since the beginning of the pandemic and remains unvaccinated, is insisting that social distancing policies should not be put back in place.

Many mayors of Brazilian cities are wondering whether they should keep scheduled end of year festivities and February's Carnival due to fears COVID-19 infection rates could soar again.

https://medicalxpress.com/news/2021-11-brazil-preliminary-omicron-cases.html

Targeting the brain’s immune cells may help prevent or treat Alzheimer’s disease

 A gene mutation linked to Alzheimer's disease alters a signaling pathway in certain immune cells of individuals with the disease, according to a new study by scientists at Weill Cornell Medicine. The team also found that blocking the pathway -- with a drug that's currently being tested in cancer clinical trials -- protects against many features of the condition in a preclinical model. The results could lead to new strategies to block the development of Alzheimer's disease or slow its progression.

The study, published Dec. 1 in Science Translational Medicine, focused on microglia, immune cells of the central nervous system that are the first to respond when something goes wrong in the brain. Studies have identified many genetic variants linked to Alzheimer's disease that are highly expressed in microglia, providing compelling evidence that alterations within these cells may play a role in the disease's onset and progression.

"Microglia are guardians of the brain under healthy conditions, but can turn detrimental in disease conditions. Our goal is to identify how they become toxic and contribute to Alzheimer's disease pathogenesis and whether we can identify immune modulators to reverse the toxicity without diminishing their normal protective function," said senior author Dr. Li Gan, director of the Helen and Robert Appel Alzheimer's Disease Research Institute and the Burton P. and Judith B. Resnick Distinguished Professor in Neurodegenerative Diseases in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine.

Alzheimer's disease is the most prevalent neurodegenerative disease in ageing, affecting approximately 46 million people worldwide. Theories point to a number of potential causes, including age-related changes in the brain, along with genetic, environmental, and lifestyle factors. These lead to the accumulation of toxic proteins in the brain -- and according to recent evidence, immune system changes -- that result in loss of neurons and their connections.

To examine how the brain's immune cells may contribute to Alzheimer's disease, Dr. Gan and her colleagues first established the molecule fingerprint of individual microglia in the brains of patients with Alzheimer's disease who carry a mutation in the TREM2 gene that markedly elevates individual's risk for developing Alzheimer's disease. TREM2 is a receptor mainly expressed by microglia in the brain, and among other functions, it signals through an enzyme named AKT to modulate inflammation and metabolism.

The team then established a mouse model by combining two strains; one that carries the AD-linked mutation in the TREM2 gene and another that exhibits Tau aggregates, one of the major pathological hallmarks in Alzheimer brains. Both patients and mice with the mutation demonstrated memory-related deficits, and their microglia expressed high levels of inflammatory molecules and exhibited an overactive AKT signaling pathway. In the mice, inhibiting AKT with a drug called MK-2206 reversed the inflammatory properties of microglia and protected against synaptic toxicity -- a type of damage to the brain's neurons that is a hallmark of Alzheimer's disease.

Importantly, because AKT signaling also contributes to the pathogenesis of many types of cancer, MK-2206 is currently being evaluated in multiple cancer clinical trials. Therefore, the safety of the drug is already under investigation.

"We identified a small molecule compound that has been tested in patients with cancer, readily enters the brain, potently modulates the brain's immune responses, and protects against synaptic loss in animal models of Alzheimer's disease," Dr. Gan said. "Our findings support further study of this compound as a potential therapy for Alzheimer's disease."

Dr. Li Gan is a co-founder with equity and consultant for Aeton Therapeutics, Inc.


Story Source:

Materials provided by Weill Cornell MedicineNote: Content may be edited for style and length.


Journal Reference:

  1. Faten A. Sayed, Lay Kodama, Li Fan, Gillian K. Carling, Joe C. Udeochu, David Le, Qingyun Li, Lu Zhou, Man Ying Wong, Rose Horowitz, Pearly Ye, Hansruedi Mathys, Minghui Wang, Xiang Niu, Linas Mazutis, Xueqiao Jiang, Xueting Wang, Fuying Gao, Matthew Brendel, Maria Telpoukhovskaia, Tara E. Tracy, Georgia Frost, Yungui Zhou, Yaqiao Li, Yue Qiu, Zuolin Cheng, Guoqiang Yu, John Hardy, Giovanni Coppola, Fei Wang, Michael A. DeTure, Bin Zhang, Lei Xie, John Q. Trajnowski, Virginia M. Y. Lee, Shiaoching Gong, Subhash C. Sinha, Dennis W. Dickson, Wenjie Luo, Li Gan. AD-linked R47H- TREM2 mutation induces disease-enhancing microglial states via AKT hyperactivationScience Translational Medicine, 2021; 13 (622) DOI: 10.1126/scitranslmed.abe3947