The latest Investing Matters Podcast episode featuring Jeremy Skillington, CEO of Poolbeg Pharma has just been released. Listen here.
Gilead’s $4.9B CD47 bet faces latest setback as company cans MDS ambitions for magrolimab
https://www.fiercebiotech.com/biotech/gileads-49b-cd47-bet-faces-latest-setback-company-cans-mds-ambitions-magrolimab
Re-educating macrophages to activate antitumor immunity: One Clever Immunotherapy
Viitala, Miro (14.04.2023)
https://urn.fi/URN:ISBN:978-951-29-9220-1
https://twitter.com/EricTopol/status/1522542891108904960?s=20&t=mIX8c2vDoVCEa5YdgKbeBw
Interferon therapy shows striking results against COVID-19
https://www.science.org/content/article/interferon-therapy-shows-striking-results-against-covid-19?utm_source=sfmc&utm_medium=email&utm_campaign=DailyLatestNews&utm_content=alert&et_rid=79504704&et_cid=4227910
"Human genetic and immunological determinants of critical COVID-19 pneumonia:
Abstract
SARS-CoV-2 infection is benign in most individuals but, in ˜10% of cases, it triggers hypoxemic COVID-19 pneumonia, which becomes critical in ˜3% of cases. The ensuing risk of death (˜1%) doubles every five years from childhood onward and is ˜1.5 times greater in men than in women. What are the molecular and cellular determinants of critical COVID-19 pneumonia? Inborn errors of type I IFNs, including autosomal TLR3 and X-linked TLR7 deficiencies, are found in ˜1-5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing autoantibodies neutralizing IFN-a, –ß, and/or –?, which are more common in men than in women, are found in ˜15-20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can apparently be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defense against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation."
https://www.nature.com/articles/s41586-022-04447-0
https://doi.org/10.3389/fendo.2021.746602
The Impact of Interferon Beta-1b Therapy on Thyroid Function and Autoimmunity Among COVID-19 Survivors
" ... Although interferon use in the multinational SOLIDARITY trial has demonstrated no significant benefits in overall mortality, initiation of ventilation, and duration of hospital stay among hospitalised COVID-19 patients, the negative results could be explained by the probably late initiation of treatment (19). Antiviral agents are likely to be most effective during the early stage of viraemia, which is before the inflammatory pulmonary phase requiring hospitalisation (20). Hence, the treatments in the SOLIDARITY trial may not work in this late inflammatory pulmonary phase of the COVID-19. Furthermore, the patient characteristics in the SOLIDARITY trial were heterogeneous, and information on SARS-CoV-2 viral load was not available...."
".... Conclusion
Interferon beta-1b treatment, even when used in the short term for COVID-19, could induce modest increases in anti-thyroid antibody titres. It was also associated with incident anti-TPO positivity during convalescence, correlating with a higher likelihood of abnormal TFTs during convalescence. If short courses of interferon treatment become a standard therapy for COVID-19, the modest changes detected thus far may indicate a phenomenon of clinical importance."
September corporate presentation. Including breast cancer.
https://www.faron.com/sites/default/files/Corporate%20Deck%20SEP%202021.pdf
More articles about interferon for Covid. This time from Boston.
Dosing administration is crucial. Which was also is included in Traumakine trial.
https://immunobites.com/2021/09/06/running-interference-in-covid-19-regulating-interferon-responses-via-sting/
"So, the important question here is: can IFNs be truly considered as a viable treatment option? And the answer is, it all depends on the timing and intensity! Too little IFNs allow the virus to replicate rapidly and without oversight. However, too many IFNs arriving at the site of infection too late can cause irreparable tissue damage."
Another new study.
https://immunology.sciencemag.org/content/6/62/eabl4340
Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths
...Fifth, in cases of SARS-CoV-2 infection in unvaccinated individuals with auto-Abs against type I IFNs, the patients should be hospitalized for prompt management. Early treatment with monoclonal antibodies (45, 46) can be administered in patients without symptoms of severe COVID-19 pneumonia, and IFN-ß can be administered in the absence of both pneumonia and auto-Abs against IFN-ß
...Seventh, given the documented innocuity and potential efficacy of a single injection, early therapy with IFN-ß may be considered for the contacts of contagious subjects or during the first week after infection, even in the absence of, or before the documentation of auto-Abs against type I IFNs, in elderly patients, who have a higher risk of critical pneumonia and auto-Abs against IFN-a2 and IFN-?, but not IFN-ß
New interferon study for back up our case.
Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19
https://stm.sciencemag.org/content/early/2021/08/23/scitranslmed.abh2624
... and hopefully also Breast and ovarian cancer:
"Modelling Macrophage Targeting in The TME Using Patient-Derived Tumor Explants 12:00 pm:
Pre-clinical and clinical development of bexmarilimab Breast tumor and ovarian ascites samples -what can they tell us about immune switch Nanostring, scRNA and cytokine multiplexing ."
https://www.nature.com/articles/s41467-021-22177-1
Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial
Theory was okay but...
Discussion:
The lack of effect of Lambda was surprising given recently described in vitro data and benefits seen in an in vivo model with early therapeutic and prophylactic administration12. There are several potential reasons for this lack of benefit:
1. A single, 180?µg subcutaneous injection of Lambda may not achieve adequate therapeutic levels of drug in the upper respiratory epithelia.
2. Second, although we attempted to randomize participants as soon as possible after the COVID-19 diagnosis was made, the median symptom duration was 5 days at the time of randomization, and 40% of participants were already SARS-CoV-2 IgG positive at enrollment.
It is possible that earlier administration, or prophylactic administration prior to established infection, would have been beneficial.
3. IFN-? has been shown to disrupt the lung epithelial barrier in mice, leading to worsened disease course and increase susceptibility to bacterial superinfection.
Furthermore, IFN-? has also been shown to inhibit influenza virus-stimulated B-cell activation and antibody production33, suggesting negative impacts on the development of adaptive immune responses critical to resolution of infection.
These data suggest the possibility that type I IFN administration may be more beneficial than type III IFN in preventing adverse outcomes of SARS-CoV-2 infection
These may negate any positive antiviral effects
So could be different with Traumakine?
Markku has told these many times:
1. Intravenous administration is much more effective
2. This doesn't change - Traumakine need also to be early administered
3. Traumakine is type I IFN
I just thought similarities with Traumakine:
+ Is this the first interferon product seeking approval for Covid ?
+ Promising, but not revolutionary, result in phase III,
- They where still using some steroids ( + Traumakine might be better if we believe Markku)
- Route is different ( + again Traumakine might be better)
https://www.reuters.com/article/uk-health-coronavirus-cadila-health/cadila-seeks-nod-to-repurpose-hepatitis-c-drug-for-covid-19-in-india-idUKKBN2BS06A
https://twitter.com/WIONews/status/1379132980812255236
Pharmaceutical company Faro's winning week: millions of dollars for lung drug research in coronary patients and promising evidence of anticancer drug effectiveness
https://yle.fi/uutiset/3-11755853