Sana results and business update

 Expect cash runway into 2025, enabling multiple data readouts across platforms for lead programs, driven by significant cash savings from manufacturing facility move to Bothell, Washington as well as research prioritization

Expect to file INDs this year for SC291 and SG295

Presented preclinical data showing survival of transplanted hypoimmune allogeneic pancreatic islet cells, cardiomyocytes, and retinal pigment epithelium cells without immunosuppression in non-human primates

Q2 2022 cash position of $579.6 million

https://finance.yahoo.com/news/sana-biotechnology-reports-second-quarter-200500692.html

Arcutis results and business update

 

• Received U.S. Food and Drug Administration (FDA) approval for ZORYVE™ (roflumilast) cream 0.3% for the treatment of plaque psoriasis, including intertriginous psoriasis, in individuals 12 years of age and older
  

• Announced positive topline results from pivotal Phase 3 trial of roflumilast foam in seborrheic dermatitis, with anticipated New Drug Application (NDA) submission in the first quarter of 2023

• Completed enrollment in INTEGUMENT-1, the first of two pivotal Phase 3 trials in subjects with atopic dermatitis six years of age and older

• Strengthened balance sheet with over $285 million from recent financings

https://finance.yahoo.com/news/arcutis-announces-second-quarter-2022-200100356.html

Probiotic to prevent infection of large intestine

 Scientists from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) have created a probiotic to restore bile salt metabolism, found in the gastrointestinal tract, to counter the onset and effects of Clostridium Difficile Infection (CDI).

CDI is the infection of the large intestine or colon that leads to infectious diarrhea, caused by an infectious bacterium known as Clostridium. Most cases of CDI have been observed to occur in those who have been taking antibiotics or just finished their course of antibiotics.

The administration of antibiotics in the treatment of CDI causes an imbalanced gut microbiome, known as dysbiosis, which can disrupt other microbiome processes such as bile salt metabolism. The dysregulation of bile salt metabolism can activate dormant Clostridioides difficile spores, leading to CDI, causing severe diarrhea and colitis -- inflammation of the large intestine, or a reinfection of CDI.

A team of researchers, led by Associate Professor Matthew Chang, from the Synthetic Biology Translational Research Programme at NUS Medicine and NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), engineered a probiotic that can detect the occurrence of antibiotic-induced microbiome imbalance and express an enzyme that can regulate the bile salt metabolism upon detection. This probiotic contains a genetic circuit that comprises a genetically encoded sensor, amplifier and actuator.

The team used an E. coli probiotic strain as the host because of its proven safety record in humans and its gram-negative nature makes it compatible with the current CDI therapy that uses antibiotics targeting gram-positive bacteria. The sensor in this probiotic, detects the presence of sialic acid, a gut metabolite that is indicative of microbiome imbalance. The actuator produces an enzyme that can regulate the bile salt metabolism, activated by the sensor, and it reduces the germination of the Clostridioides difficile spores that causes CDI, when induced by the sialic acid sensor. The team also included an amplifier in the probiotic which amplifies the activation by the sensor and increases the production of the enzyme, reducing the germination of the Clostridioides difficile spores by 98%. Experiments showed that the probiotic significantly reduced CDI in laboratory models, as demonstrated by a 100% survival rate and improved clinical outcomes.

Assoc Prof Chang is encouraged by this advancement that sheds more light on the gut environment and how it can be manipulated to create less invasive treatment strategies. He says, "This scientific innovation gives a better understanding on how we can control the microenvironment in the body, without needing to exert direct lethality to kill the Clostridioides difficile bacterium, give additional drugs, or use invasive methods to rid the infection. Our perspectives have shifted towards studying how we can come up an antimicrobial strategy to complement and assist the natural biological processes in the body to help limit the onset of infection. This is useful when considering the development or improvement of future therapeutics for CDI."

Story Source:

Materials provided by National University of Singapore, Yong Loo Lin School of Medicine. Note: Content may be edited for style and length.

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Journal Reference:

1. Elvin Koh, In Young Hwang, Hui Ling Lee, Ryan De Sotto, Jonathan Wei Jie Lee, Yung Seng Lee, John C. March, Matthew Wook Chang. Engineering probiotics to inhibit Clostridioides difficile infection by dynamic regulation of intestinal metabolism. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-31334-z

https://www.sciencedaily.com/releases/2022/08/220804102617.htm

New therapeutic drug for Alzheimer's disease without inflammatory side effects

 Although Aduhelm, a monoclonal antibody targeting amyloid beta (Aβ), recently became the first US FDA approved drug for Alzheimer's disease (AD) based on its ability to decrease Aβ plaque burden in AD patients, its effect on cognitive improvement is still controversial. Moreover, about 40% of the patients treated with this antibody experienced serious side effects including cerebral edemas (ARIA-E) and hemorrhages (ARIA-H) that are likely related to inflammatory responses in the brain when the Aβ antibody binds Fc receptors (FCR) of immune cells such as microglia and macrophages.

These inflammatory side effects can cause neuronal cell death and synapse elimination by activated microglia, and even have the potential to exacerbate cognitive impairment in AD patients. Thus, current Aβ antibody-based immunotherapy holds the inherent risk of doing more harm than good due to their inflammatory side effects.

To overcome these problems, a team of researchers at KAIST in South Korea has developed a novel fusion protein drug, αAβ-Gas6, which efficiently eliminates Aβ via an entirely different mechanism than Aβ antibody-based immunotherapy. In a mouse model of AD, αAβ-Gas6 not only removed Aβ with higher potency, but also circumvented the neurotoxic inflammatory side effects associated with conventional antibody treatments.

Their findings were published on August 4 in Nature Medicine.

"FcR activation by Aβ targeting antibodies induces microglia-mediated Aβ phagocytosis, but it also produces inflammatory signals, inevitably damaging brain tissues," said paper authors Chan Hyuk Kim and Won-Suk Chung, associate professors in the Department of Biological Sciences at KAIST.

"Therefore, we utilized efferocytosis, a cellular process by which dead cells are removed by phagocytes as an alternative pathway for the clearance of Aβ in the brain," Prof. Kim and Chung said. "Efferocytosis is accompanied by anti-inflammatory responses to maintain tissue homeostasis. To exploit this process, we engineered Gas6, a soluble adaptor protein that mediates efferocytosis via TAM phagocytic receptors in such a way that its target specificity was redirected from dead cells to Aβ plaques."

The professors and their team demonstrated that the resulting αAβ-Gas6induced Aβ engulfment by activating not only microglial but also astrocytic phagocytosis since TAM phagocytic receptors are highly expressed by these two major phagocytes in the brain. Importantly, αAβ-Gas6 promoted the robust uptake of Aβ without showing any signs of inflammation and neurotoxicity, which contrasts sharply with the treatment using an Aβ monoclonal antibody. Moreover, they showed that αAβ-Gas6 substantially reduced excessive synapse elimination by microglia, consequently leading to better behavioral rescues in AD model mice.

"By using a mouse model of cerebral amyloid angiopathy (CAA), a cerebrovascular disorder caused by the deposition of Aβ within the walls of the brain's blood vessels, we also showed that the intrathecal administration of Gas6 fusion protein significantly eliminated cerebrovascular amyloids, along with a reduction of microhemorrhages. These data demonstrate that aAb-Gas6 is a potent therapeutic agent in eliminating Aβ without exacerbating CAA-related microhemorrhages."

Professors Kim and Chung noted, "We believe our approach can be a breakthrough in treating AD without causing inflammatory side effects and synapse loss. Our approach holds promise as a novel therapeutic platform that is applicable to more than AD. By modifying the target-specificity of the fusion protein, the Gas6-fusion protein can be applied to various neurological disorders as well as autoimmune diseases affected by toxic molecules that should be removed without causing inflammatory responses."

Professors Kim and Chung founded "Illimis Therapeutics" based on this strategy of designing chimeric Gas6 fusion proteins that would remove toxic aggregates from the nervous system. Through this company, they are planning to further develop various Gas6-fusion proteins not only for Ab but also for Tau to treat AD symptoms.

This work was supported by KAIST and the Korea Health Technology R&D Project that was administered by the Korea Health Industry Development Institute (KHIDI) and the Korea Dementia Research Center (KDRC) funded by the Ministry of Health & Welfare (MOHW) and the Ministry of Science and ICT (MSIT), and KAIST.

Other contributors include Hyuncheol Jung and Se Young Lee, Sungjoon Lim, Hyeong Ryeol Choi, Yeseong Choi, Minjin Kim, Segi Kim, the Department of Biological Sciences, and the Korea Advanced Institute of Science and Technology (KAIST).

Story Source:

Materials provided by The Korea Advanced Institute of Science and Technology (KAIST). Note: Content may be edited for style and length.

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Journal Reference:

1. Hyuncheol Jung, Se Young Lee, Seongjoon Lim, Hyeong Ryeol Choi, Yeseong Choi, Minjin Kim, Segi Kim, Yujean Lee, Kyung Ho Han, Won-Suk Chung, Chan Hyuk Kim. Anti-inflammatory clearance of amyloid-β by a chimeric Gas6 fusion protein. Nature Medicine, 2022; DOI: 10.1038/s41591-022-01926-9

https://www.sciencedaily.com/releases/2022/08/220804130537.htm

bluebird bio results and update

 - beti-cel for beta-thalassemia PDUFA goal date is set for August 19, 2022 -

- eli-cel for cerebral adrenoleukodystrophy PDUFA goal date is set for September 16, 2022 -

- Ended quarter with $218M in restricted cash, cash and cash equivalents

and marketable securities -

https://finance.yahoo.com/news/bluebird-bio-reports-second-quarter-200500307.html

FDA eyes dividing Jynneos doses into fifths to up monkeypox vax supply

 The Biden administration is considering splitting doses of the smallpox vaccine, which are being used to prevent monkeypox amid the current outbreak, into five smaller doses, the head of the Food and Drug Administration (FDA) said Thursday.

FDA Commissioner Robert Califf said during a briefing that his agency was looking into possible solutions to increase the number of available doses of the Jyenneos vaccine. One of these proposed solutions is dividing the current doses into fifths.

“We’re considering an approach for the current doses of Jynneos that would allow health care providers to use an existing one dose vial of the vaccine to administer a total of up to five separate doses,” Califf said. “This approach which we’re referring to as dose-sparing, would change the method of administration for Jynneos which currently administered subcutaneously.”

According to Califf, this proposed change would involve injecting the reduced Jynneos doses in between layers of skin, creating a “pocket” for the vaccine.

“There’s some advantages to intradermal administration, including an improved immune response to the vaccine,” Califf said. “It’s important to note that overall safety and efficacy profile will not be sacrificed with this approach.”

An FDA spokesperson told The Hill this change in the monkeypox vaccination strategy was being considered because it had become “clear to all of us that we would not meet current demand with the current supply.”

“As we often do at FDA, we began exploring other scientifically feasible options. The identification of a clinical study that demonstrates that this approach could work has been particularly useful in informing how this might work without sacrificing the safety and efficacy of the vaccine,” said the spokesperson.

If pursued, this new strategy would still involve two doses administered about 28 days apart.

James Krellenstein, co-founder of the LGBTQ+ healthcare advocacy group PrEP4All, noted on Twitter that the FDA’s decision appeared to based on a 2015 study that looked into the immune response derived from a one-fifth dose of Jynneos administered intradermally compared to a full dose administered subcutaneously, which is when the shot is injected into the layer of fat beneath the skin.

The study, funded in part by the National Institute of Allergy and Infectious Diseases, found that an “equivalent immune response” between the two different forms of Jynneos administration.

Krellenstein wrote he was glad to see this decision being considered, saying his organization had suggested this strategy to federal officials multiple times.

https://thehill.com/policy/healthcare/3588440-fda-considering-dividing-jynneos-doses-into-fifths-to-increase-vaccine-supply/

Cytokinetics results and update

 Advisory Committee Meeting to Review NDA for Omecamtiv Mecarbil Scheduled for December 13, 2022; PDUFA Target Action Date Set for February 28, 2023

Company Revises 2022 Financial Guidance; Reduces Projected Spending for 2022

https://finance.yahoo.com/news/cytokinetics-reports-second-quarter-2022-200000742.html