Ryan Mee, CEO of Fulcrum Metals, reviews FY23 and progress on the Gold Tailings Hub in Canada. Watch the video here.
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@hemoknowledge
When/how is it decided to escalate the dose?
@stu
Almost all CAR T-cell treatments cause Cytokine Release Syndrome (CRS), perhaps all. Naturally, the grade of CRS is important (1-4). Five to eight years ago, grade 3-4 were unacceptable. Nowadays, grade 3 is tolerable and sometimes even grade 4 can be managed, though it is considered to be life-threatening.
My understanding is that phase 1 is a dose escalation clinical study with safety as primary readout. This means that the researchers will start with the lowest dose of cells. This will allow them to avoid life-threatening situations. This also means that it is highly unlikely that the first patient will cause the termination of the study.
Stewy darling, just a thought, what do you think the chances are of a small meteorite entering your rear end and exiting through your gob, thus rendering you a sad lifeless vegetable ? Nice if it happened.
... an AML diagnosis was a 1 -2 year lifted sentence.
...but here we are now, HEMO-CAR-T is about to commence clinical trials, and there is hope for others (this is no time for further delays).
Cyrox have you forgotten about all the years of research and development which will put odds in favour of CT success. Its not as binary as you suggest. You have more reason to be confident than not.
Cyrox.. what a stupid assessment!
There were a range of excellent products being worked on. Good progress with any and I was looking at profit. Now it seems to be based to an extent on the outcome of a trial on one person. If it works or at least is safe we get to see what happens. If this fails the need to raise at a discount will trash this company for years.
Can't quite believe that my investment is now a bet on a single outcome.
STU485...just wtf is wrong with you???
You are correct in noting that Phase 1 trials are primarily designed to evaluate safety and tolerability, rather than efficacy. The emphasis on efficacy in my posts was driven by a common interest in the potential treatment outcomes, but this certainly should not overshadow the importance of safety data.
Regarding the typical CRS incident rate in CAR-T treatments it varies widely depending on the specific CAR-T construct and the patient population. Generally CRS occurs in approximately 50% to 90% of patients treated with some of the more common CAR-T therapies like those targeting CD19 in B-cell malignancies. Most cases are mild to moderate and manageable with standard treatment protocols including the administration of tocilizumab an IL-6 receptor antagonist approved specifically for severe CRS.
With regard to whether or not the trial would be stopped if the first patient where to react with severe CRS? I think it would depend. It is of course a possibility, however If the CRS was severe but could be managed effectively with standard protocols (as has been the case for some other approved CAR-T therapies) and measures could be taken to mitigate future risk the trial could continue with adjustments and would need to be discussed with FDA/ethics committee. I do have a tendency to focus on the positive because I am positive about Hemo's product candidates but in the interests of balance there a risk that the trial could fail because of safety reasons.
😂🤣 thank you Digittt that cheered up my day 🤣
I wasn't aware you had to be diagnosed as being elderly
Haywain, your recent posts regarding Ph1- first patient are all efficacy related.
We all know Ph1 is predominantly a safety study, so why no mention of safety stats?
In your defence and on a very quick look, I can’t see any asking for your scientific and unbiased opinion on safety, so let me please.
Could you please advise the typical CRS incident rate with Car T treatments ?
Also, in the unfortunate event of a severe CRS incident in Patient 1, do you believe the trial would continue?
Thanks in advance.
AIMO
DYOR
Now I feel spoilt ! Thank you
Here you go:
Venetoclax (Venclexta):
In combination with hypomethylating agents or low-dose cytarabine, venetoclax has shown overall response rates (ORR) ranging from 50% to 70% in newly diagnosed elderly patients unfit for intensive chemotherapy. In RR AML, the response rates might be lower, generally expected around 20%-30%, depending on the combination and patient specifics.
Gilteritinib (Xospata):
For patients with RR AML harboring FLT3 mutations, gilteritinib has demonstrated a composite complete remission rate (CRc, including complete remission with partial hematological recovery) of approximately 20%-30%.
Ivosidenib (Tibsovo):
In patients with an IDH1 mutation, ivosidenib has shown a CR+CRh (complete remission with partial hematologic recovery) rate of around 30% in clinical trials.
Enasidenib (Idhifa):
For RR AML patients with IDH2 mutations, enasidenib has shown a CR+CRh rate of approximately 20%-30%.
Gemtuzumab ozogamicin (Mylotarg):
Response rates for gemtuzumab ozogamicin can vary, with CR rates around 15%-20% in the setting of RR AML, depending on the specifics of the patient population and treatment regimen.
Decitabine and Cedazuridine (Inqovi):
As an oral formulation of a hypomethylating agent used in more accessible settings, the response rates are similar to intravenous decitabine, typically in the range of 15%-20% for CR in RR AML settings, but can vary based on combination therapies.
Thanks so much - some homework over the weekend. Have a good one !
Sorry missed a bit - FDA do allow tweaks along the way depending on what those tweaks are if they are unforeseen tweaks that are beyond the parameters that have been defined in the IND then a discussion / supplement to IND may be required prior to proceeding.
Well in the case of RR AML where patients have limited options due to the aggressive nature of the disease and it’s resistance to standard treatments I would imagine even modest response rates are significant. I can’t put an exact value on it but for instance 20-30% of patients responding whether that be complete response or partial response would probably be considered promising enough to proceed to further trials: anything better than that is very promising. Because the are so many intra patient variabilities it is difficult to say whether or not you would be able to determine signs of efficacy in a single patient - but if you did see any sign of response in the first patient infused it would be significant. In RR AML where effective treatment options are desperately needed even small improvements in response rates can be clinically significant. Maybe to get an understanding of what constitutes success look at the clinical data from Ivosienib, Enasidenib, Gemtuzumab or Gilteritinib in terms of response rate - think Venetoclax is used off label too for RR AML.
Question for Haywain - again - sorry!
In my simple mind the car t is developed and in its final form. So when we inject our first patient we should have an insight into how the product works as a whole right? Do the fda allow tweaks along the way if needed? What does a successful phase 1 look like in percentage terms in your experience?
Thanks as always!
Haywain, no sign of recruiting patients yet ???
https://clinicalresearch.pennmedicine.org/us/en/
Haywain ... That is what makes the current share price even more crazy and stupidly low. I am sure if we hear that trials are started and there is even a glimpse of positive news, this will fly. From a finance perspective, I think that is what is holding many people back and also this is not a get rich overnight scheme.
Nevertheless, my understanding is that if they are burning through around $400k per month and they raised $4m in Feb, they probably have until Nov to get the initial results and finalise a deal with a big pharma to fund the future. Since CBR and CDX will need big funding, the hope is now on CART being successful.
Don't think it has much to do with prevail the number of patients tested they are just monitoring the trial and analysing the data - comes down to recruitment (how many patients are currently being treated for AML at the centre for clinical, how many go on to have RR AML and of those which meet the criteria of having FLT3 overexpression and of those how many sign the consent form to have a new CAR-T treatment. When you put it in this context you can see that it can take a while to get a study going considering AML will affect less than 1 in 10000 . About 75K living with AML in the states currently and about 20K new diagnosis per annum. Having said that the patients who do go on to have RRAML have very little treatment options left to them save perhaps bone marrow transplant which requires a donor with a matching human leukocyte antigen (which takes time - unless already available from databased donors) and a horrendous conditioning regimen which most older patients wouldn't survive anyway. So I think there is a very good chance that the trial will successfully recruit.
MrI I think he quickly tagged :hoped" to "more than one" and you would expect this with Prevail Infoworks' expertise. Have novdoubt we are I Phase 1 the preparation pre injection is vitally important so work very much front loaded. The injection and monitoring is a sit and wait situation and if the preparation and science is good we should get some success. On the money situation Prevail are vested in the business and are probably holding back on further support but I cannot see them
holding back if absolutely needed. It would be like standing by and doing nothing to save the sinking ship you are relying on to get to shore and the land of plenty or CBR. We are going to be okay. GLA
The interview was great except he stated he "hoped" that they would be able to inject 1 patient in 2024. That seems to imply that the start of the trials is some time away. I truly hope I am wrong since what news is going to make this share move?
I like towards the end of the interview where he states we are already in Phase 1 trials with everything going on. I read that as the prep and getting ready to start to start injecting patients which we all hope will provide a cure for these folk.
Maybe trying to stimulate share price? I’ve never seen such a static stock in 34 stock market years. Suppose the only thing that will change this is news but still, there’s not much range in this one.