I think the increased dosage was to take full advantage of the properties of Idronoxil as indicated by its ability to block repair of DNA damage in order to optimise chemotherapy-induced tumour damage whilst minimising non-tumour toxicity via inhibition of ENOX2.
The following video from GK explains the increased dosage is to give a higher chance of obtaining an abscopal response (
, from 19:25-19:45). The higher dosage must have also been informed by the current pharmacokinetics study (results not yet released,
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378739), since a higher and more frequent doses runs the risk of the drug accumulating to toxic levels, so I presume they already have access to the pharmacokinetic data to help them inform the DARRT-2 study and subsequent regulatory submission, plus I think I heard GK say in one of his interviews that the data they already have access to indicates they could use a higher dose.
Sure, they will also evaluate the pharmacokinetics of this higher dose in the patients from the DARRT-2 study and use this information to inform future clinical trials, but the strategy for IONIC is different to DARRT-2 and LuPIN.
For starters, DARRT-2 is designed to obtain conditional approval for NOX66 via an expedited pathway should it achieve its expected primary outcome of improved overall survival after 12 months, starting in Q1 2021 and likely ending in 2023. The trial is going to be double-blinded, so NOX will not know the full results until the final readout in 2023. Sure, there may be interim analyses, but I don’t think NOX will risk having to make adjustments for type I errors in order to take a early peek at the data. Even if there is the option for early termination for overwhelming efficacy, I think NOX will prefer the trial runs to completion since it is a first-of-its-kind treatment and the more data it obtains the better the chances when it comes to obtaining FDA approval.
The IONIC trial is essentially a P1/P2 pilot study looking at response rates for various cancers in ~30 patients and will readout every 2-3 months after it starts in Q1 2021. BMS may help finance a P2/P3 trial if the results look good but licensing it may be a bit premature since it is difficult to gain any meaningful information that could facilitate a licensing agreement from only 30 patients, keeping in mind the splits based on the different types of cancers treated. Maybe they will purchase the rights to license, which could be equivalent to the sum needed to run a sizeable phase 3 clinical trial.
The results of the LuPIN study will be released in Q1 2021, so Novartis will be in a position to enter early negotiations with NOX. However, these negotiations will be specific to late-stage prostate cancer, not other cancers. An agreement with Novartis will also have its own issues since I don’t think Lu-PSMA-617 is FDA approved. It is also currently being trialled with several other treatments, so Veyonda will have to compare favourably with these other treatments first before Novartis makes any type of licensing decision. In saying that, NOX will be in a very lucrative position if it turns out Novartis requires Veyonda to obtain FDA approval for Lu-PSMA-617.
Correct me if i’m wrong but Noxcovid is a P1 study? The Noxcovid study is a bit of a farce in my opinion. NOX applied for regulatory approval in April, but only received it in September – and they are only currently recruiting in Maldovia (
https://clinicaltrials.gov/ct2/show/NCT04555213?term=nox66&draw=2&rank=3). Despite record high case, death and ICU admission rates in Maldovia, NOX appears to be struggling to recruit the 40 patients it needs for the study. This is even more shocking when you see the low threshold needed to be eligible for this study. This seems to be part of a recurring pattern where NOX appears to struggle to recruit patients into a clinical trial in a timely manner.
Conservatively, it appears to me 2021 won’t be very lucrative for NOX at all. The number one asset for NOX will be the DARRT-2 study, followed by LuPIN and IONIC. The cash burn is high and unless NOX enters into a partnership with BMS or Novartis in 2021, there probably will be another capital raise. I hope NOX doesn’t overextend itself, especially so early on in its lifetime, and without any real successes to date. This company could be a future success, but its too early to tell.
(20min delay)