Helping Survive Cytokine Storm
Why is there a wide range of health risk associated with COVID-19?
Covid-19 and even the common influenza can be fatal under certain conditions. The complications that can lead to advanced morbidity and even mortality are often related more to the immune system’s heightened reactivity to the infection. Patient predisposition to exacerbated immune and inflammatory response leads to a phenomenon called ‘cytokine storm’ – an overloaded assault by immune system cells and biochemicals. This is, in fact, the mechanism by which thrombosis and other events in many Covid-19 patients lead to risk of mortality.
Cytokines are small proteins released by many different cells in the body, including those of the immune system. They coordinate the body’s response against infection by, in part, serving as a beacon for immune cells and triggers to amplified inflammation. The body’s response to infection can go into overdrive if this cytokine activity is not managed by the inbuilt feedback mechanisms. For example, when SARS -CoV-2 – the virus behind the Covid-19 pandemic – enters the lungs, it triggers an immune response, attracting immune cells to the region to attack the virus, resulting in localised inflammation. In some patients with predispositions to immune overreaction, excessive or uncontrolled levels of cytokines are released which then activate more immune cells, resulting in hyperinflammation. The risk factors for such patients can include but are not limited to obesity, advanced age, autoimmune disease, asthma and diabetes. Patients with one or more of these conditions can be seriously harmed and even expire by way of Covid-19. Even those that survive can have long-term, life changing health consequences
Cavaltinib™ has been shown in published research to inhibit these cytokines at a central upstream mechanism that reduces the transcription (production) of many causal cytokines that drive these diseased states and this work has subsequently led to approval by Health Canada for a clinical trial for what appears to be a good COVID-19 drug candidate. Cavaltinib™ inhibits the nuclear pathway responsible for generating as many as 150 of these related cytokines and immune chemicals to slow the rate and intensity of the inflammation. The objective with the administration of this treatment is to mitigate the amplitude of the ‘cytokine storm’ activity allowing the body to combat the infection in a controlled manner and preserving and protecting healthy tissues from the exacerbated inflammatory response. The ultimate goal with this strategy is to protect those vulnerable and have them make it through to the antibody stage – adaptive immunity. Those who manage and survive this inflammatory storm are then able to develop naturally derived antibodies and will go on to recover, and in most cases build naturally acquired immunity against re-infection. It’s an effective way to acquire herd immunity with antibody generation to many of the viral proteins and not just a few selected proteins that these novel vaccines may induce.
These findings are published in peer-reviewed literature accompanied in our case reports by unpublished research. Cavaltinib™ is shown to inhibit the key inflammatory cytokines including and especially IL-6, which are central to the systemic status of the inflammatory response. Clinical trials on alternative drugs have targeted just one cytokine and that’s only part of the solution. Cavaltinib™ inhibits multiples of these cytokines central to this ‘storm’ to lower risk for morbidity allowing the patient to avoid dangerous levels of inflammatory activity and hospitalisation. As a result, the infection can be experienced like that of a more common influenza course; and lead to long term protection most likely, even, to coming variants of the virus.
How & Why Was Cavaltinib™
The principal researcher who cleared the path to this drug discovery did so for personal reasons. Initially driven by a passion to better understand nutraceuticals and nutrition in order to enhance performance during his quest to win the title of several North American bodybuilding competitions, Franco Cavaleri was struck with the raw reality of a diagnosis for ulcerative colitis, a serious autoimmune disease.
This disease derailed Cavaleri twice with hospitalization and with a prognosis of surgical intervention with prohibitive lifestyle consequences but was also the impetus that changed Cavaleri’s course of research forever. Cavaleri’s research into anti-inflammatory strategies, originally used to support recovery from training, quickly became focused on better understanding the pharmacology of natural medicinal agents to rehabilitate his ulcerative colitis, without surgical intervention. Cavaleri was able to overcome the ravages of his disease without surgery!
According to Cavaleri, the key was to isolate an extract instrumental in reducing inflammation, however, the extract as it was just didn’t have the potential to deliver pharmacology impactful enough to allow him to live a completely asymptomatic lifestyle. Cavaleri was able to unravel the pharmacology of each constituent isolated in this technology at a cellular and subcellular level in multiple cell lines and tissues. In this way, Cavaleri discovered a way to predict the activity and further engineer the final outcome to function with more selectivity on target subcellular proteins involved in the development of disease pathology and symptoms. The original indication studied was ulcerative colitis, however, with the inception of COVID it was clear that the COVID pathology was characterised by similar features of the autoimmune disease pathology and upon a deeper investigation of the historical research at Biologic, both Health Canada and the Biologic team agreed that this drug candidate could play a significant role in the treatment of COVID and the alleviation of the strain the infectious disease was having and continues to have on the health care system.
Empowering a potent future depends on our cultivation today
Health experts including the top U.S. infectious disease expert Dr. Anthony Fauci have long called for a convenient pill that patients could take when COVID-19 symptoms first appear, much the way the standard flu medication Tamiflu helps fight influenza. Such medications are seen as key to controlling future waves of infection and reducing the impact of the pandemic. The variants of this virus will continue to cycle and infect the human population year after year; mutation after mutation.
We, at Biologic Pharmamedical Research, a parent company to Oltre Biomedical Inc., have been talking this language since March of 2020, insisting that treatment by oral pill is the way to go. It is the least intrusive, most reliable way to override the risks that infection poses. This validates our model and demonstrates how open the market is to such strategies. We believe Merck’s and Pfizer’s antiviral oral treatments can deliver very successful outcomes for some patients; however, we still stand confident that the Cavaltinib™ pharmacology fits into this treatment program as a synergistic or alternative mechanism of treatment.
Additionally, the indications we are targeting expand beyond COVID to respiratory disease in general and furthermore, to additional indications we have our sights on.
The antiviral treatment currently popularized is an orally active inhibitor of viral proliferation preventing viral replication by selectively binding to viral proteases (e.g., HIV-1 protease) and blocking protein precursors that are necessary for the production of infectious viral particles. It was originally developed as an inhibitor of HIV protease.
This treatment attempts to block the production of the virus with 70% effectiveness. This new Cavaltinib™ drug inhibits inflammation by way of a newly discovered mechanism (MSK-1 kinase pathway). Combining the antiviral treatment with the selective Cavaltinib™ would be powerful in eliminating severe infection and death rates utilizing different additive mechanisms of action, simultaneously, to convey relief. Nevertheless, we have NO associated side effects, and the antiviral treatments have a significant load of adverse events associated with them that may void them as treatment options for many patients.
In addition, and just as important, the COVID dilemma provides us with fast-tracking regulatory paths to drug status based on the urgency the pandemic poses. This accelerated push to drug status by regulatory bodies then opens the door to take this newly established drug to new and additional indications that we are very confident, based on historical experience, are achievable. Our objective is to pursue with vigor additional applications for Cavaltinib™ with new clinical trials evaluating and garnering approval for these new indications - ulcerative colitis, Crohn’s disease, rheumatoid arthritis, and more.
Notice of Authorisation for Clinical Trial for Biologic Pharmamedical Research*
*Biologic Pharmamedical Research is the parent company of Oltre Biomedical Inc.