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The forthcoming presentations of CF33 at ESMO 2023 in Madrid...

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Harry58

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937

05/10/23

02:35

Post #: 70179347
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Originally posted by Watmighthavben ↑

Vaxinia, making history in 2023

Cancer is said to inflict up to 39% percent of humans, with close to 1 in 7 humans dying from the disease. In addition to cancer and for that matter heart disease, there have been many endemic human diseases throughout history that have ravaged through communities. Pandemics have contributed to waves of deaths including the Influenza pandemic (1918-19) 20-40 million deaths; black death/plague (1348-50), 20-25 million deaths, cholera 40 million deaths, AIDS pandemic (through 2000) 21.8 million deaths, and more recently COVID, responsible for 6.95 million deaths to today and still counting. Tuberculosis is said to have killed an estimated 1 billion people, and finally Malaria, is believed to have caused more deaths in human history than any other disease. Thankfully due to the work of scientists including Louis Pasteur, laboratory techniques for creating vaccines were introduced in the 19th century, and as a result many of these pandemics have been successfully treated by vaccines.

Yet one disease in 1796 had a much higher fatality rate than cancer, that being smallpox, with a death rate of 30%. The vaccine which ultimately cured smallpox was developed by British Doctor Edward Jenner, who proved that an infection with the relatively mild cowpox virus, would confer immunity to the deadly smallpox virus. In other words infection with one virus, was used to kill another more deadly strain of a virus. Wikipedia tells us that subsequently the origins of the smallpox vaccine became murky over time. Allan Watt Downie demonstrated in 1939 that the modern smallpox vaccine was serolodicallv distinct from cowpox, and a virus known as vaccinia was subsequently recognised as a separate viral species. Whole-genome sequencing has since revealed that vaccinia is most closely related to horsepox, and the cowpox strains found in Great Britain are the least closely related to vaccinia. When it was realised that the virus used in smallpox vaccination was not, or was no longer, the same as cowpox virus, the name 'vaccinia' was used for the virus in smallpox vaccine. (See wikipedia for more).

Since it was reported that a 42-year-old female patient with myelogenous leukemia underwent tumor remission after an influenza infection, the attempt to use viruses to eliminate tumors has never stopped. The anti-tumor effect of oncolytic viruses acts in two ways, firstly by directly infecting and lysing tumor cells, or secondly by arousing the immune system to generate an immune attack. One individual working tirelessly to manufacture an oncolytic virus to kill cancerous solid tumour cells is Professor Yuman Fong of the City of Hope medical research facility in California. Over recent decades Professor Fong came up and developed the idea of utilising a strain of the vaccinia virus to infect and kill cancerous solid tumours within humans. Fong’s 33rd strain of the virus, known as Vaxinia, was amazingly successful pre-clinically in killing cancer within mice and human xenograft models, killing all cancers against the NC1 60, (i.e., the most frequently studied human tumor cell lines in cancer research). But unfortunately when he came to dose in human patients with his virus, COVID struck. The Food and Drug Administration Authority were understandably not to keen to infect humans with one virus, when another was running rampant throughout the community. History again shows us when the “arm to arm method” was employed as a living form for transporting viruses, using orphans as carriers, this method was problematic due to the possibility of spreading other blood diseases, such as hepatitis and syphilis. As an example, in 1861 forty-one Italian children contracted syphilis after being vaccinated by the "arm to arm" method. So Professor Fongs plans to infect humans with his novel yet potent strain of the Vaccinia virus, entitled Vaxinia, were placed on hold for up to two years. This was hugely disappointing for not only Professor Fong, but for the biotech company Imugene (IMU-ASX), who had licensed the drug from the City of Hope facility.

Most importantly the vaccinia virus vaccine was shown to not cause a smallpox infection because it does not contain the smallpox virus. The vaccinia virus proved successful in curing smallpox due predominantly to the immune response generated in patients with the lethal disease. In essence Vaccinia contains within its genome genes for several proteins that give the virus resistance to interferons. Interferons are a group of signalling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defences. The strain of vaccinia developed by Professor Fong entitled Vaxinia, is an oncolytic virus (OV), that only infects the cancerous cells in a humans body, not the healthy cells. Vaxinia kills the tumor cells by infecting and replicating specifically in tumor cells leading to direct lysis of tumor cells. Malignant cells have defects in antiviral responses allowing Vaxinia to replicate and lyse the malignant cells in a cancer patients body. Vaxinia therein induces different types of immunogenic cell death, including necrosis, necroptosis, immunologic apoptosis, pyroptosis, and autophagy. It’s a somewhat complicated process to explain, though OV’s such as Vaxinia enhance tumor antigen presentation and prime the immune response in the tumor microenvironment through the induction of antiviral responses, inflammation, cytokine production, and expression of costimulatory molecules. The infection of vascular endothelial cells by OVs such as Vaxinia, destroys tumor vasculature, resulting in tumor necrosis and the infiltration of immune cells into the tumour microenvironment.

Despite these attributes many oncolytic viruses have been unsuccessful in treating cancer in humans as they have been either too toxic, or unable to penetrate the solid tumours themselves. Locating these solid tumours within a patients body is a difficult task. Unlike lineage markers expressed by hematologic (i.e., blood) malignancies, markers expressed on solid tumors are less tumor-specific and cannot be targeted without possible damage to essential tissues, increasing the risk of toxicity. Hence the development of Imugene’s oncarlytics platform, where CD19 expressed targets are effectively “painted on” solid tumours, making them easily identifiable to the incoming oncolytic virus. Though back to Vaxinia for now, and an update on the viruses progress.

In short the FDA did finally allow Professor Fong to dose in human patients with Vaxinia back in May 2022. The issue of toxicity was prevalent, therefore the FDA made Fong start out administering relatively low doses of Vaxinia. Thankfully even at low doses Vaxinia was still found to be virulent enough to turn tumours from cold to hot, making them easily identifiable. As a consequence Keytruda, a successful monoclonal antibody drug has been now added with Vaxinia in the current Vaxinia (MAST) Trial into up to 100 patients in Australia and the US. Given the solid tumours are hot, inflamed and primed with Vaxinia, its hoped Keytruda can easily identify them and “go to work” as it were, with the application of its inherent anti cancerous properties. Professor Fong is travelling to Australia this week, and shall no doubt provide the public with an insight into how effective this combination process has been in eradicating solid tumours.

So far Yuman Fongs post clinical in human trials for his oncolytic viruses CF33 and Vaxinia have proven safe, low in toxicity and successful in turning tumours from cold to hot. Unique nHIS imaging enables the trial supervisors to visualise the virus progression within the patients body. They have produced images of the virus traversing from one solid tumour to another. Patients with breast cancer who were injected with the virus into their right side, are now showing the virus present in their left side tumour cells. The process is most remarkable is it not? To think Professor Fongs virus is actually infecting and replicating within solid tumours in patients. Even more profound is the identification of necrosis (i.e., cell death) within the patients solid tumours. On his recent visit to Australia Professor Fong stated emphatically he was seeing “unequivocal signs of cancer killing within humans”. An astonishing admission from the Vaxinia founder, to say the least. Professor Fongs revelation has since been confirmed by the CEO and Managing Director of the Vaxinia licensee company, Imugene (IMU - ASX), wherein she noted Vaxinia is “definitely working within solid tumours”. Definitive proof of these statements is set to arrive this year, as biopsies from the patients in the existing trials have been sent to the lab for analysis, a process to followed by peer review and publication. No doubt that day is sure to bring interest from not only Imugene investors, but the public at large, including Big Pharma, who at this stage have been unable to tap into the lucrative “holy grail” of cancer medication, that being the treatment of solid tumours within cancer patients. Solid tumours contribute to up to 90% of all in human cancer indications.

Astoundingly Professor Fongs Vaxinia trial is being administered both intratumorally and intravenously in multiple solid tumour types, including to the best of my knowledge colon cancer, colorectal cancer, triple negative breast cancer, pancreatic cancer, non-small cell lung cancer, urothelial cancer, metastatic melanoma, bladder cancer, head and neck cancer, renal cell cancers and gastrointestinal cancer. Professor Fong is aiming to establish with his current trial that if Vaxinia is found to be effective in treating these solid tumour types, then it is capable of treating all solid tumour types. The most opportune outcome for Professor Fong, taking all things into consideration, would be for Vaxinia to be accepted by the FDA as “significant breakthrough technology”, thereby granting the drug fast track approval into a registrational trial, whereby medical practitioner’s could prescribe Vaxinia to their cancer patients at the request of the patients oncologist. This outcome may be closer than many in the medical and indeed investment community had envisaged, as oncologists are said to be lining their patients up in droves to participate in the existing Vaxinia Trial. If indeed Vaxinia is approved for in human administration to the public, this shall not only be a huge feather in Professor Fong’s cap, but Imugene as well, for having the foresight and vision to license the City of Hope drug. Approval of Vaxinia would not only lead to the public being able to access the drug, but potentially hundreds of combination partners could be seen to “knock on Imugene’s door,” seeking access to collaborations and combinations with Professor Fong’s breakthrough technology. The ability to identify solid tumours alone is a boon for CAR T and allogenic therapy providers, who up until this point in time have only been successful in combatting blood cancers (i.e., melanoma), as opposed to the much broader solid tumour market. Whilst monoclonal antibody drugs such as Keytruda (see above), would be in a position to benefit from combinations with Vaxinia, given the viruses propensity to turn solid tumours from cold to hot, in a safe, low toxic manner with minimal side effects and positive results. An added advantage of these affiliations would be the noticeable fact that Vaxinia is cheap to produce and in plentiful supply. The ability to dose the drug intravenously, as noted by me previously, provides huge benefits to governments, health professionals and regulators as well, due to the ease of administration and the reduced in hospital time for patients receiving the drug, At present long bouts of chemotherapy and the huge cost of drugs such as Keytruda are sending alarm bells though the health sector worldwide.

There is a lot riding on Vaxinia and the extent of its effectiveness in treating solid tumours within cancer patients. If successful I am confident our grandchildren shall someday be reading of Professor Yuman Fong and Vaxinia on Wikipedia, alongside Edward Jenner, Louis Pasteur and the other notable scientists recognised in this post. We may not know the full extent of Vaxinia’s success in treating humans by the end of this July, but if Wikipedia does one day feature the drug Vaxinia alongside the phrase curing solid tumours within cancer patients, I for one am hoping the year 2023 rates a mention.

DYOR Seek investment advice as and when required Opinions only

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The forthcoming presentations of CF33 at ESMO 2023 in Madrid (20/10/2023) and Vaxinia at SITC 2023 in San Diego (1/11/2023) are eagerly awaited by shareholders.

At the ESMO conference I am expecting to see published results of third party reviewed data of cancer cell biopsies and news headlines along the lines of ... First in human trial of CF33 oncolytic virus confirms that it detects, infects and kills solid tumor cancer cells.

The CHECKvacc Phase 1 Trial in TNBC is in the 4th cohort of a six cohort design with an estimated study completion date of December 1st 2023.

As noted previously the published results will not include Cohort 4, however it will update the results of Cohort 3 which were last presented data up to October 2022 at ACCR 2023 in April. Note in an interview discussing the dose escalation to Cohort 3 Leslie quoted this as the potential sweat spot for the study.

While there has been much conjecture that the SITC 2023 conference will provide some indication of data efficacy I note that the presentation is a Trial in Progress Poster which according to ASCO guidelines ...
"trials in progress are ongoing and have not reached pre-specified end points for analysis and as such inclusion of results would be improper and is strictly forbidden"

The Vaxinia MAST trial is a 14 cohort design in both monotherapy and combination with Pembrolizumab administered by intra-tumoral injection and intravenous infusion.
The progress though this trial has been exceptional as we are now in the final two cohorts in monotherapy and with only two cohorts remain in the combination therapy.

The majority of cohorts in the MAST study have been dosed at 1x10^7 and there has been no safety concerns to date. This is truly an exceptional outcome.

And while we wait for news of the first patient in on the OnCARlytics OASIS trial I am confident that CF33 will deliver on its promise to obliterate solid tumor cancer cells.

Special thanks to the great team at Imugene under the leadership of LC to progress these trials through the clinic.

GLTAH - Go Team Imugene

IMU Price at posting: 4.4¢ Sentiment: Buy Disclosure: Held
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