Sounds legit @Solvetheriddle based on their announcement two days ago: Opthea-Announces-COAST-Phase-3-Trial-Topline-Results.PDF. They may not trade again from here on that basis, i.e. being insolvent now.

Had this on my watchlist too. Very unusual that Phase 3 would be this bad. Does make you wonder how this got through all the other phases.

It does happen @edgescape - after all phase 1 is really mostly to do with safety and side effects, and phase two does address efficacy but on a limited number of patients where you can actually get lucky with the results, or unlucky, because of the lack of scale. Phase 3 trials being so much bigger, with many more patients across multiple centres usually, is where the important data comes from, that is far more relevant. From what I've briefly heard in this case - as I don't follow this company - there was basically no difference in the results between the control group and the people receiving the drug, so that's something you'd hope to pick up in Phase 2 for sure.

A company I made money on years back, Sirtex Medical had a similar result at one point (in 2017) in a trial of their yttrium-90 resin microspheres (called "SirSpheres") when the study / trial found that SRX's microspheres did not extend survival significantly compared to Bayer’s sorafenib (the standard treatment for liver cancer at the time) in a study of patients with hepatocellular carcinoma (liver cancer). Although the 459-patient trial did not meet its primary endpoint (extending life), the company reported that patients treated with its microspheres experienced less than half the number of severe, treatment-related adverse effects than those who received the standard, twice-daily systemic treatment with sorafenib, so it wasn't a complete wash-out, but it was bad enough.

Sirtex's CEO at the time, Gillman Wong, was widely criticised for trying to elevate SirSpheres to a standard of care treatment for Liver Cancer instead of a salvage treatment that improves quality of life and had less side effects than other treatments. It had been Wong's decision to make "extending life / improved survival rates" the primary endpoint of that trial, and that primary endpoint was not met, whereas if improved quality of life including less pain and less adverse side effects had been the primary endpoint, it is far more likely that the primary endpoint would have been met. Mr Wong was wrong, they said, and he was also caught selling his Sirtex shares during a period in which he wasn't allowed to sell them, ahead of those trial results being released I reckon it was (from memory), so he was dismissed and replaced and Sirtex Medical went on and a little later got taken out at a decent premium by a Chinese consortium led by CDH Investments in a deal that outbid a previous offer from Varian Medical Systems, so a good result in the end, particularly because the treatment (SirSpheres yttrium-90 resin microspheres) went on to improve the quality of life of a significant number of people with liver cancer.

I have also heard of other drugs that looked promising right up to the Phase 3 trial stage and then failed at that hurdle, and were not progressed further after that, but none come to mind right now. But it happens unfortunately. It's a very risky area to invest in.

I remember Sirtex. It was a pretty large holding for me back then. I think the important difference for Sirtex compared to OPT is Sirtex was a fast growing, profitable, dividend paying (how many biotechs do that?) company looking to expand the use case for y90 SS. In that instance, as they had solid growth already in the salvage market they had to power the trials to extending life. In the case of OPT, the trials were to prove the treatment had any use case. Very different risk profile to Sirtex, but very much standard pre rev biotech (which I avoid).

Gilman Wong was lucky to avoid prison over his insider trading.

One of the reasons I was (over)confident was that the phase 2 trial was quite large, 366 patients. And had VERY positive results. +5.7 letters with a p value of 0.0002 in one prespecified group.

I still think this is probably worth zero. But there is a chance with the second phase 3 trial. The COAST trial which just failed, was in combination with a drug called aflibercept. The SHORE trial, which is due to report in "mid CY2025", uses Opthea's drug in combination with ranibizumab, the same combo that was used in the phase 2 trial.

There is a chance that for some unknown reason, Opthea's drug works in combo with ranibizumab, but not alibercept. If that were the case, the drug would obviously have some value, greater than zero at least. Or perhaps the phase 2 results were just an anomaly and it really doesn't work at all. But that would be strange. Statistically, a p value of 0.0002 means that there is only a 2 in 10,000 possibility of the result being due to chance.

@Bear77 @UlladullaDave

Thanks for that

Thinking again IXC is another one that I now remember which failed the phase 3 trial and the share price tanked on the news.