Antibe Therapeutics Inc(Pre-Merger) ATBPF

RE:RE:Anybody considered the rough ride CINODS had?

[PoorOpinion]

StrikingMoose wrote: Did you read the 86 or so page rejection paper? I did



The main reasons it was rejected were mainly twofold.

1) The drug promised no increase in BP compared to naproxen
The half life of NO releasing moeity was only 2h compared to naproxen at 12h. It caused wild fluctuations in blood pressure as the vasodilating effects came on so strong and left so rapidly and left 10h without any effect on BP, at which time blood pressure moved towards hypertensive because of the naproxen

2)The drug promised increased gastric safety
The drug promised increased gastric safety compared to naproxen due to assumptions NO would provide some gastric protective effects. In rat models using NO donors the rats still had gastric lesions in ~10% of subjects compared to ~15% with naproxen (cannot remember exact numbers. I read this a while ago and it was a massive read)

The last factor that was one direct reason they rejected it was because naproxinod was a pro drug. It cleaved in the digestive tract into a separate NO releasing moeity and naproxen. The fact was pointed out that it would be just as effective to provide the 2 agents on their own which you could titrate doses of NO based on wish instead of having only 1 choice.



The dose used in humans IIRC was 500 or 750mg of naproxen BID as well as the H2s releasing moeity. They made note that the pill was very large, I believe the second largest size of pill available on the market in order to fit both drugs in. Naproxinod still required BID dosing.




Now comparing to ATB346

- Complete elimination and REVERSAL of gastric lesions in rodent and canine models (I've stated in the past canine are better than rodent) compared to smaller yet still significant and present gastric lesions in rodent models with naproxinod
- ATB346 is NOT a pro drug. It is a new molecule that itself or a metabolite causes both the cox suppression and H2S release
- The pills are much smaller, and once daily dosing. Yes they do care about this
- The dose is 16% of naproxen compared to what they used in naproxinod and 1/7 the dose of naproxen they are using in the trials
- H2S stops leukocyte adherence (which causes the initial injury in ulcers as Dr Wallace has discovered and completely re-wrote the understanding of ulcerative injury) and NO does not. 
- H2S induces neutrophil apoptosis and is used to generate ATP in mitochondria with the most efficacy specifically in the mitochondria of the gastric mucosa

I am SO happy that he helped to create and try push naproxinod to market because they learned all the potential shortcomings and pitfalls years ago and had a decade to perfect it. 

I think that perhaps if you are so unsure of your investment here you should do some very purposeful research especially if you have an appreciable amount of money invested as many of us do.

But all that H2S effect is hypothetical when it comes to the drugs ACTUAL mechanism. And it turns out the lack of an ACTUAL mechanism was a weakness for the regulators for naproxcinod. You have to be clear when stating whats a hypothesis and whats a fact, I know the regulators will be.
I'd love to have the belief that the present trial puts to bed all the doubts about this drug, which is how this board seems to sees it, but clearly it doesnt. I hope I'm wrong.

I take your point Wallace has to have learnt from the naproxcinod experience.