Dr. David Bar-Or
Thank you, Michael. And good afternoon, everyone.
So today, we'll update you on some of the research advances Ampio has accomplished in the past few months. And first, I would like to mention that this work is a result of intense efforts by a very talented science team of molecular biologists, biochemists, computational biologists and regulatory specialists under my direction and supported by our experienced and world renowned scientific advisory board members. I will try to simplify this update, but I recognize that some of this research topics are not trivial and maybe difficult to follow for people not familiar with this scientific concept. A comprehensive science presentation to the scientific advisory members and to the Ampio Board of Directors was made last month that included all our advanced discoveries in inflammation pathways associated with Ampion treatment of acute kidney injuries, COVID-19 and the rare children condition of protein losing enteropathy, or PLE, in post Fontan procedure. It is important to emphasize that Ampio, as Michael said, is not just an osteoarthritis of the knee or OAK company or a COVID-19 company. The scientific research being pursued with Ampion pertains to inflammation in general. OAK, COVID-19, acute kidney injury, et cetera, are just examples of inflammatory conditions that are currently being investigated and which support the anti-inflammation platform technology of Ampion. The whole team and I are very excited by this new understandings of the modes of action of Ampion and the enormous potential of this biologic drug to treat many debilitating inflammatory condition without side effects. This is particularly meaningful to me as a physician who encountered for many years in practice patients suffering from inflammation consequences and for whom no remedies existed beside the steroids.
Now we have, in my opinion, I believe, a safe alternative.
One of the most important you finding is the inhibitory activity of Ampion on toll-like receptor, TLR7.
So toll-like receptors are fundamental cellular mechanism, by which innate immune cells respond to pathogens like bacteria and viruses. And in particular, our interest was in the recognition by this receptor of single-stranded RNA sequences, like in the SARS-CoV-2 virus of COVID-19. There are about 11 different known toll-like receptor with various functions. TLR7 is of particular interest to us because it is activated by the COVID-19 virus, which in turn results in a cascade of intracellular events that may lead to a cytokine storm. And its activation is also involved in many other inflammation conditions, such as acute kidney injury, lupus, sepsis, and others. Ampion significantly inhibits the activation of this toll-like receptor 7. Experiments conducted on immune cells from patients and stimulated with a specific known activator of that TLR7 receptor was blocked with Ampion and significantly present -- prevented up to 96% of the release of [indiscernible] cytokines and chemokines, like IL-6, TNF alpha, IL-1 beta, interferon gamma, CXCL10 and many others very important mediators of inflammation.
While many pharmaceutical companies' strategies target single cytokines like IL-6, for example, Ampion significantly affected multiple cytokines that are responsible for severe inflammation, like the cytokine storm of COVID-19. The inhibition of toll-like receptor 7 is critically important in treating many other inflammation-related conditions.
Another very important finding was that we are directing macrophages to become the M2 type anti-inflammatory macrophage. Macrophages are immune cells whose primary function is to remove debris from inflammation site and damaged cells and also to recruit other immune cells to the area of inflammation by secreting cytokines to attract them. The transformation into anti-inflammatory macrophage to M2 is achieved by changing the kind of cytokines that this macrophages make and by upregulating some healings, small fat molecules called prostaglandins. These are associated with termination mechanisms of inflammation. Inflammation is beneficial, if controlled by its duration and by its magnitude. Ampion affects both by limiting the duration of inflammation with the prostaglandin and with its magnitude by reducing the amount of pro-inflammatory cytokines. This is an important effect that is essential and unique to Ampion in sharp contrast to steroids and nonsteroidal anti-inflammatory agents, which suppress healing.
Another important observation was made by stimulating immune cells with the COVID-19 spike proteins. The spike proteins are the protrusions on the virus membrane that give the appearance of a crown, hence called the corona virus. It is the protein that allow the virus to get attached to our cells and mediate the introduction [indiscernible] of the virus into our cells. It is the protein to which antibodies are directed against and the basis of all current vaccine for COVID-19. When we use immune cells from a normal individual with no previous exposure to the virus and stimulated with spike proteins from various sources, the U.K. variant, the Wuhan original virus and the South African variant, no reaction occurred in terms of cytokine release, but its immune cells.
However, when a vaccinated individual immune cells were used under the same conditions, a large cytokine release occurred that was significantly attenuated by 70% with Ampion. This suppression emphasizes the fact that Ampion prevents the dysregulated and intense immune response caused by the virus. It also demonstrates the presence of the memory cellular immunity that is not antibody mediated and is rarely mentioned. The fact that the level of antibodies to the virus declines over time is a normal occurrence with any antibody. It does not mean that we lost immunity.
We have stored memory cells able and ready to react with the re-exposure. We now believe this Ampion effect could form the basis for a new test to demonstrate the presence and magnitude of cellular immunity. This is important in clinical trials where efficacy of treatment and assessment of immunity are usually done by PCR, measuring how much virus there is or what level of antibodies are present without assessing the presence and the potential of memory cellular immunity. There is also the possibility that part of the virus, the virus RNA, is reverse transcribed into our genome. The viral RNA is copied and introduced to our DNA like it happens in retroviruses like HIV. The recent preprint article by Harvard and MIT scientists demonstrated this in vitro. The newly inserted RNA will cause viral proteins over time, and maybe partially responsible for the long haul syndrome described in post-COVID patients. In that regard, we are initiating a clinical trial long haulers with persistent respiratory symptoms by administering Ampion through nebulization inhalation. We hope to attenuate the symptoms that long haulers experience. And now the very important finding with significant clinical implication is the discovery that Ampion upregulates the expression of a protein called thrombomodulin. Thrombomodulin is a receptor on the surface of endothelial cells, the inside lining cells of blood vessel. It is a docking site for a protein called thrombin. Thrombin mediates the formation of blood clot and is increased in inflammation. In essence, the upregulated thrombomodulin attaches the thrombin molecule and in that way, neutralize its procoagulation effects. This is important in COVID-19 where multiple reports of blood clots have been observed in another medical condition such as sepsis. In essence, Ampion neutralize an important mechanism of clot formation in inflammatory conditions by upregulating the most important protein in thrombomodulin. It has important clinical application for patients with increased risk of blood clots.
Finally, in a previous press release, we reported on the similarity of gene regulation between Ampion and dexamethasone, a strong glucocorticoid steroid. We highlighted similarities and differences between the 2. We propose that like dexamethasone, Ampion has anti-inflammatory properties but without the harmful side effects of steroids as demonstrated clinically in many clinical trials. I like to use the analogy example of 2 different antibiotics with different modes of actions against a certain bacterium. Both will kill the bacteria.
However, one is extremely potent, analogous to steroids and will damage other nonbacterial components indiscriminately, while the other is more targeted plus less potent but without having a global effect on targets that are not that bacteria. Many examples exist of steroids using inflammation-mediated diseases with complete immunosuppression, many accompanying side effects. In contrast, Ampion is proven to have similar anti-inflammatory effects, but with a robust safety profile. We argue that in some inflammation conditions where dexamethasone or other steroids used, they could be substituted by Ampion.
We are in the process of composing several manuscripts of this and other findings to be published in scientific peer reviewed journals. Several abstracts we published in scientific peer reviewed journals. Several abstracts have been already submitted for targeted scientific conferences. Thank you.