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"My analysis may indeed be incorrect, so any comments from the...

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Harry58

237 Posts.

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26/11/23

17:58

Post #: 71113714
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Originally posted by Watmighthavben ↑

Some people asked me to explain the Vaxinia Trial in more detail with respect to dosage rates, and why I thought the trial might start to show better results than it had already, as the trial progresses. I am unsure how far up the therapeutic window Professor Fong wishes to take dosage rates in the trial, but we do know the current cohorts are now being dosed at 100 times more than the first cohorts, and 10 times more than the last cohorts dosed. We have not received any results for the patients dosed recently at 10 parts to the 8, i.e., (100,000,000), those being the current cohort of patients. All arms including those being dosed with Vaxinia on its own, as a monotherapy, or in combination with Keytruda, are now being dosed at 10 parts to the 8, the highest dose thus far.

Vaxinia - an interesting chain of events

The first patients in Imugene’s Vaxinia Trial were dosed in May 2022. They were dosed at 10 parts to the 6 or 1,000,000 particles.

Then on October 31, 2022 Imugene announced that its Phase 1 MAST (metastatic advanced solid tumours) study evaluating the safety of novel cancer-killing virus CF33-hNIS (VAXINIA) had advanced with the first patient dosed within intratumoral (IT) cohort 2 of the trial. This was at 10 parts to the 7 or 10,000,000 particles

Then on November 2, 2023 Imugene announced One Complete Response (CR)* in bile duct cancer in the mid dose on study for over 350 days

Nb. It was not clarified but one would assume the complete response was from a patient dosed in October 2022 at 10 parts to the 7 or 10,000,000 particles, as opposed to 10 parts to the 6, i.e., 1,000,000 particles.

Reading between the lines it is a pity the 10 parts to the 6 dosed patients are calculated in the overall response percentages, given the exceptionally low doses afforded them as a result of stringent FDA conditions imposed on the trial. But I guess what is really exciting is that

4. On November 2, 2023 Imugene announced Cohort 5 of the IV arm for the monotherapy dose escalation is now open as is IV cohort 3 of the combination study. These patients were dosed at 10 parts to the 8 or 100,000,000 particles, that being TEN TIMES MORE than the previous cohorts.

Professor Fong when in Sydney at a presentation in March of this year was very excited to see how Vaxinia would combine with pembroluzimab (i.e., Keytruda). He had stated previously that suggested CF33-hNIS increases the expression of a checkpoint protein, which can improve the efficacy of immune checkpoint inhibitors, such as pembrolizumab. “Oncolytic viruses have already been shown in animal models to be as effective as combination therapy with many other immunotherapies, including checkpoint inhibitors and CAR T therapies. We are hoping the CF33/ Vaxinia platform will move rapidly to clinical testing in combinations with these and become effective combination immunotherapies in the treatment of human cancer,” said Professor. Fong. This is of particular interest to me as the patients in the combination arm of the trial have only just been dosed at the highest dosage rate thus far, that being 10 parts to the 8. It's going to be interesting to see how they progress in the new year.

The higher the dose the greater the efficacy? The higher the dose the greater the percentage of positive signals? These outcomes are unclear as of now, but one would have to assume that if Vaxinia works, as Professor Fong says it does, then higher amounts of the virus in a patients body would have a higher chance of eradicating cancer, than smaller doses.
CF33-hNIS Vaxinia was designed to replicate in tumor cells, in order to facilitate a large immune response against the tumor cells. One would think the higher the dosage rate, the higher the level of virus replication. That said when initiating the trial researchers noted that besides providing durable protection, a small dose of oncolytic viruses can be effective against the tumor due to the ability of the virus to replicate and spread in the tumour cells. I would note that Vaxinia can enhance the immune system’s ability to recognise tumor cells, creating a memory against the tumor antigens, which can help prevent cancer recurrence. Therefore even though the majority of patients in the initial cohorts experienced what is referred to as disease stabilisation (SD), trial supervisors are not ruling out the potential for some of these patients moving into the partial response (PR), if not complete response (CR) category.

What is 10 to the 6th power? [Solved]
The value of 10 raised to the 7th power is equal to 1,000,000.

What is 10 to the 7th power? [Solved]
The value of 10 raised to the 7th power is equal to 10,000,000.

What is 10 to the 8th power? [Solved]
The value of 10 raised to the 8th power is equal to 100,000,000.

My analysis may indeed be incorrect, so any comments from the scientists, mathematicians or medico's among us on the trial, dosage rates or anticipated outcomes, would be appreciated. I myself am starting to get excited now. I was reading through cancer survival stories this morning, and although I read of one earlier stage patient surviving colorectal cancer, I didn't read of any late stage pancreatic, liver or bile duct cancer patients surviving after their disease had metastasised. I do hope there have been some, but am hoping even more that if so, Vaxinia can add to that list. I'm probably even more excited as its been well over 14 days since the last patients were dosed at the highest dosage rate, and no significant safety concerns or fatalities have been reported. The trial is therefore still ongoing. Great news for patients and investors alike!

Enjoy your Sunday WMHB

DYOR Opinions only

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"My analysis may indeed be incorrect, so any comments from the scientists, mathematicians or medico's among us on the trial, dosage rates or anticipated outcomes, would be appreciated."

Thanks Ben, for your post and ongoing quality contributions to these threads.

The recent poster presentation at SITC 2023 released on 6th November 2023 provided an excellent insight into the Dose Escalation Scheme for the Vaxinia MAST trial.

A Phase I Safety and Tolerability Study of VAXINIA (CF33-hNIS), a Novel Chimeric Oncolytic Poxvirus, Administered Intratumorally or Intravenously in Adults with Metastatic or Advanced Solid Tumors.

https://static1.squarespace.com/sta...99224552384/SITC MAST TIP_final 14Oct2023.pdf

In this presentation we saw the initial 16 cohort design be expanded to 26 cohorts with a dose escalation in both IT and IV for monotherapy and combination to extend to 3x10^9 i.e. (3 billion virus particles). The plan is now to test up to 150 patients in this expanded design.

It is worth noting that as cohorts progress through the therapeutic index they are dosed at 1x and 3x for each log of the index.

The graphic below from the poster presentation has now been updated by the recent announcement on 2nd November - Cohort 5 of the IV arm for the monotherapy dose escalation is now open as is IV cohort 3 of the combination study.

So yes, very exciting times indeed as we wait for the next data readout of the MAST trial.

I am looking forward to the day when the primary end points of this study are released, and the esteemed Professor Yuman Fong can release the news to the world with thunderous acclaim and deserved applause that he has indeed claimed the holy grail.

GLTAH - Go Team Imugene
.
IMU Price at posting: 8.4¢ Sentiment: Buy Disclosure: Held
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