RE:RE:Deliberate ObfuscationForgive my longwinded comment...
Re Langosta’s discussion around what CR, PR, NR mean in real terms…..
Not sure if this is duplication but thought I could chime in on the definitions. I work in thryoid cancer so have some knowledge of the area. Not huge and a very different cancer.
If you treat a patient and the drug is taken up and generates ROS in some or all cancer cells, they will be killed. If some remain, the immune response triggered by TLD1433 may finish off the cancer cells.
At 90 days, if they take a urine sample, spin it down and look for tumour cells (that are usually shed into the bladder) then that is the cytologic evaluation. They also look with a camera. No cells in the cytology and nothing seen on visual = CR. If they can' see anything on camera but the urine has some cells that would be PR. Called partial because it is still good that you cannot see the cancer but you know that it is still holding on based on cancer cells found on the spin-down. If both cancer cells and visual inspection find cancer that would be NR.
With all cancer therapy it comes down to survival. Cancer cells are, by definition, cells that are not following the rules and replicating and growing and jumping off to new locations (metastases). If you kill most with our treatment, great. But if a few survive and, given enough time, they will show up in the urine and then get big enough that they can be visualized again. That would be a CR converting to a PR or NR.
So Langosta, the response categories are not about whether the drug was taken up or not as I think the science suggests that it is always taken up in some cells. But some cells may be harder to reach or not take up as much. Or the light doesn't reach them well enough.
So the classification is not based on No tumour destroyed or some but rather whether you kill enough that there is no shedding in the urine and you cannot see any on the scope.
The maintenance treatment is meant to chase down surviving cancer cells and kill them (I assume).
As the follow up protocol progresses from 90 to 180 and so forth, you are essentially giving the cancer cells that survived a chance to proliferate enough that you can find/see them and say that they are not CR but rather PR or NR.
The phase 1 b patients were interesting because 2 of the 3 patients were one and done and cured. It seems to me that if not back by 360 then likely fully killed off. The other interesting thing about the phase 1b patients that I didn't appreciate till the recent publication was that they had multiple tumours spread around the bladder. One cured patient at 2 discrete tumours and the other 3. That means that the study drug killed off 5 discrete foci of malignancy. That is pretty cool. In my mind that meant the therapy penetrated and worked 5 times at complete success in those patients. I know that that is kind of inflating it but it gives you more appreciation for the drug.
Why the recent results are not quite as good going forward is big question. I wonder if they did a few extra treatments or different doses or light delivery...who knows. In the big picture I think the phase 1b patients show us that the ability to cure is there and that science still needs to figure out the best protocol to get the job done. FDA applications mostly require you to do things the same way, within reason, so it isn't that they can play around with different things at this stage. If they get fully approved then you would easily see researchers doing variant protocols where they treat at 0 and 1 month or two weeks apart or every combination imaginable to figure it out.
The other immunotherapies (most of the competition) work by trying to instill the drug in the bladder over and again and triggering immune attack on the cancer cells. I call this a whack-a-mole approach because you want the immune system to chase the cancer cells and kill them faster and more of them then are escaping and replicating. It is my feeling that a lot of immunotherapy CR’s are not true CR’s but just situations where you have killed enough of the cancer cells that you are ahead of the game and cannot see them anymore. But start spacing out the drug or stop it and I feel like the relapse rate steadily increases with time. Some are cured but I suspect most are not. Still helps but TLD1433 has the potential to be curative for some.
Like all the other holders (I'm a medium holder) I do worry when . I have zero doubt that if you treated 100 patients then the results would be fine. I do worry that the near term results are decent but not so stellar that BTD is going to happen tomorrow. It might be one of those situations where they hold the cards till they feel it is a given rather than risk an early application and rejection.
Things that give me confidence
- The current numbers are still at Keytruda levels despite the 12 under-treated.
- The most in the know people in the company buying a bunch more with the warrants. He would be the one that knows the data the day it arrives at headquarters, on every patient. I’ve read that he is a type A micromanager. Good.
- Cure of 2 extremely resistant to treatment patients in phase 1 b is exciting. It is different than curing two cases that were more routine (with only one tumour per bladder, for example).
- Somehow they had the connections to swing a free lab setup from Li Ka Shing. Someone knows someone and was able to impress. That give me hope that there are people in the mix that are dealmakers and networkers and can swing some funding (JV?) when the time comes.
- The majority of shares are held by longholders. Many of whom hold big chunks ( a million here and million there) and collectively add up. Those people cannot change prices swings when 0.05% of shares are traded on a day (many days). All you need is a few random holders or player and that can happen. Those people do have the power to contribute to big price jumps on good news since they are the reason that there are no big chunks of shares readily available (I suspect). RDW and wife’s warrant exercise got them 750,000 new shares. Trying do that on the open market would have meant buying every share available for at least a week or two. That would not have been easy.
So still here. Hopeful for the medium term and very hopeful for the long term but wouldn’t be surprised if near term swings all over.