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Just an observation that the ph2 is intended to run over 3 years so costs, I assume, would not all be year 1.

I would expect the voucher program to be renewed upon expiry. It's true that the medical countermeasures (MCM) PRV legoslation was not renewed (2023) but in that case there were a number of influential voices against this given that the DOD also provides sponsorship to the srug company.

We still don't know much about the efficacy of the drug. From the last clinical update by Dr Connely, 16 patients had been treated with doses of between 500 and 1500mg. They were due to treat up to a further 12 patients with the 2000 (3 patients) and 2500mg (3 plus 6 patients) doses. If treatment is dose dependant then I would expect improved outcomes for these later patients. It has taken 2 years to treat 16 patients so to complete by the fall must mean they have shifted a gear. Glioblastoma has a dismal survival. If they demonstate a significant improvement in progression free or overall survival, that will be a considerable achievement.

If you watch the video on the GBM Agile trial here https://virtualtrials.org/video2024.cfm?video=202404 , at minute 47 they talk about costs. Due to the AGILE trial design, they have managed to reduce costs for participating companies to around 1/3 of normal ph2 costs. There are Glioblastoma trials that have been fully funded by the NIH. ReSPECT-GBM is supported by an award from the National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH), and is funded by a three-year $17.6M grant by the Cancer Prevention & Research Institute of Texas (CPRIT).

I see that there have been various data releases at ASCO '24 in the US over the weekend., It's one of the largest and most prestigeous cancer conferences in the world and a good announcement does wonders for a company's SP. If we ever get the RNS confirming that the good doctor is preaeneting at ASCO 25, its would be very good news...

Dr. Connelly answers a question on the phase 1 status at around the 30 minute mark in the this presentation.

https://youtu.be/QgzE34enGj0

That doesn't really tie in with the trial timescales. If you look at clinicaltrials.gov, the end date is December 2025. Also, in the last update video, it was disclosed that they had paused for further toxicology tests. They were due to reopen at the 2000mg dose and the move on to the 2500mg and if that proves tolerable, a further 6 people will be treated at the recommended ph2 dose.

"One of the primary mandates of BPCA is to prioritize and sponsor clinical trials of therapeutics in pediatric populations. Doing so requires collaboration among NICHD, other NIH institutes, non-government organizations, and the U.S. Food and Drug Administration (FDA)."

I had a quick look on clinicaltrial.gov and found this sponsored Glioblastoma trial... "Testing the Use of the Immunotherapy Drugs Ipilimumab and Nivolumab Plus Radiation Therapy Compared to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Unmethylated Glioblastoma"

ClinicalTrials.gov ID NCT04396860 Sponsor National Cancer Institute (NCI).

Agile is still running - new drugs can be added as and when they thw organisatiion running the trial approves thwir inclusion. It woukd make alot of sense for GaM to be included in twrms of cost reduction and scientific rigour....

Thanks for highlighting. Very good news for patients. Interesting that the clinical trial was open label. If MCW run a similar trial for Glioblastoma, it would make recruitment potentially easier as all participants would be on drug.

Https://virtualtrials.org/newsarticle.cfm?item=8595

Interesting that there is no mentiin of working capital. I was under the impression they were just about out of cash based on thw run rate of the previous few years. Maybe the imaging business is now at least covering its costs?

So looks like the foubdation is working on a fund to cover the full cost of the EAP. They must have real faith in the science. Offering the drug free on an EAP in the US (with its high drug cost) would, I suspect, raise the profile of GaM massively.

I would suggest it is basically saying the maps provide a more accurate assesment of the extent of tumour than a radiologist would otherwise determine by looking at the same MRI images (that are used as input for the map generation software). This improved accuracy helps the surgeon remove maximal tumour (interoperative MRI) which I think is called resection. The maps are also seem to help predict the prognosis for the patient.

But I am no expert :-)

It's unfortunate that the latest video was taken down by IB after only 1 day. I watched the presentation during the brief time it was available. Two points were standout. Firstly, they have now started recruitmemt at the 2000mg dose.. This is important because, as I understand it, the dosing used so far is way below that used in the pre-clinical animal models which demonstrated increases in PFS. If efficacy is dose dependent, then it would seem the 2000mg and 2500mg patients are likely to derive most benefit. Given the terrible prognosis for recurring disease, it should be possible to detect an efficacy signal in the near term. Secondly, Dr Connerley stated that the team were going to be analysing samples of tumour taken from trialists (post-treatment) as well as measure drig levels in blood. These actions give the investigators a better understanding of how much drug is in the body and its effect on glioblastoma at a cellular level. This is all part of the "discovery" process of first-in-man use (for this indication). I would expect 2024 to be a year of potentially very meaningfull news. So far, it seems GaM has been very well tolerated with little or no side effects. Given the serious side effects of existing standard of care (Chemo & Radiotherapy), I imagine the potential for a low/no side effects treatment that extends survival, by even a few months, is high. TTF, (Optune) which is approved sadly extends survival by only a relatively short period and requires using the appliance for long periods.

As you said, it seems like a basic mistake, probably by management. I'm sure they have learned from this and don't imagine a short delay will have any real implications. The FDA are engaged and now expecting a revised application so it's not like starting from scratch.

I find it hard to believe anyone from the clinical team actually submitted the original request. According to the FDA ODD database, GaM has been designated for (1) glioblastoma and (2) atypical teratoid/rhabdoid tumours. Indeed, in all of the phase 1 presentations, by Dr. Connelly, it is explained that the WHO has classified brain tumours based on certain genetic characteristics and makes a point of differentiating between glioblastima and lower grade(s) glioma.

Thanks. Will be interested in the response

I watched it. Looked like an internal presentation to MCW staff. I wonder who posted it and whether they had permission.. Possibly not!

Thanks for this. I've watched a few of these now and learn snippets of new information every time. It's great to see really thorough clinical testing taking place while also looking to accelerate avaiability through an EAP.

The results presented are interesting but I'm not sure you can read too much into the efficacy results. its worth bearing in mind that tbey are only now reaching ph1 doses somewhere closer to that used in the preclinical animal studies (50mg/kg/day). Given that GaM is thoughr to effectively "crowd out" iron in the cancer cells, I would have thought that efficacy would be highly dose dependant. In which case, we may see a stronger efficacy signal in the two additional cohorts (2000mg and 2500mg) recently added. Encouraging to hear they are well on the way to closing out recruitment given the 6 month timescale quoted.