RE:RE:RE:RE:Feature article about Theralase on biotuesdays.com website
Eoganacht wrote: Our current trial is for high risk BCG unresponsive NMIBC. The percentage of NMIBC patients that can be categorized as BCG unresponsive is quite large:
"
Approximately, one-third of the NMIBC patients will not respond to BCG. Among those who demonstrate an initial response, more than 50% will experience recurrence or progression during long-term follow-up." (
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997797/ )
So far we have full 450 day results for 29 patients from this unresponsive population. The problem is that 12 of the 29 were undertreated and 5 of the 12 were removed from the trial prematurely. Despite these issues we have achieved a substantially better durable CR rate than Keytruda and this should be good enough for FDA approval. So the future looks bright for the use of TLD1433 pdt for high risk NMIBC. IMHO our CR rates will continue to improve through the rest of the trial and at some point in 2023 Theralase should see an improvement in it's financial situation such that it will be possible to exploit more of it's IP. We may even see a renewal of interest in TLD1633 which had a 15% greater kill rate of cancer cells than TLD1433. In 2018 Dr. McFarland wrote:
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Considering the potency of TLD1633, it may seem odd that TLD1433 was selected instead. TLD1433 was prioritized over the other compound for a number of reasons, including: (1) there were more synthetic steps required for producing TLD1633, and those steps were low yielding (unoptimized at that time) and required expensive catalysts, (2) there was more batch-to-batch variability with TLD1633, (3) the theranostic capacity of TLD1433 was greater (i.e., its luminescence quantum yield was higher), and (4) we were relatively far along in our pre-clinical studies with TLD1433 by the time the synthesis of TLD1633 was optimized to produce the larger batches required for in vivo studies."
Hopefully we will see phase 1b trials this year for GBM and NSCLC using systemic administration of PS's and low dose radiation activation. Then in 2024 we may see a phase 1 trial of Theralase's anti-pathogen vaccine.
What is still an unknown is how well TLD1433 would do as a first line treatment for NMIBC after TURBT. The reasons a patient is BCG unresponsive may have little relation to the reasons a patient does not respond to TLD1433. While TLD1433 pdt may be more effective than BCG in treating NMIBC, this has yet to be demonstrated.
CancerSlayer wrote: Wildbird1 wrote:
"Let's recap very briefly...
1) Merck BCG treatment is used to treat early stage bladder cancer patients.
2)The only reason TLT is giving 2 treatments is that the patients that the FDA gave to TLT were patients that did not respond to any standard treatment protocol(untreatable patients).
3) If TLT was used to treat early stage Bladder cancer patients(like Merck BCG), the CR%(complete response) would go through the roof.
4) On early stage Bladder cancer patients , we can easily assume that 1 TLT treatment would be more than enough to achieve CR.
Large pharma deal...
When TLT will strike a deal with a large Pharma, you can bet your shirt that this big pharma first step will be to cooperate with TLT to start a trial to use TLT treatment for early stage Bladder cancer patients, in order to become the standard of care for NMIBC, and get the big market$ for NMIBC.
Right now TLT trial is for replacing " Radical Cystectomy" (removal of the Bladder).
Question?
What are the chance of TLT treatment displacing Merck BCG treatment as the standard of care for NMIBC?
The answer could be in this link...
https://my.clevelandclinic.org/health/treatments/17908-bacilius-calmette-guerin-bcg-treatment
Under "BCG treatment schedule"
" The initial BCG cancer treatment occurs weekly for six weeks, This is called induction therapy.
If the treatment is working, your doctor may prescribe BCG maintenance therapy.
Maintenance therapy is given once a week for three weeks at the three-, six-and 12 month marks. For some patients this may be continued up to three years".
The above is over 15 BCG treatments for just 1 course of treatment.
In the "Eoganacht Article" TLT said that some patients need 2 course of BCG treatments before achieving CR.
15-30 Merck BCG treatments versus 1 TLT treatment...Yes there is a big possibility TLT treatment could replace Merck BCG treatment as the standard of care for NMIBC.
The possibility of TLT treatment replacing Merck BCG as the standard of care for NMIBC could add a lot's of $value to a big pharma deal.
BTD application.
Dr.Mandel said " The company plan to apply for FDA BTD in first quarter of 2023 on the basis of the phase 2 clinical study date collected to date"
"Collected to date"mean the necessary data for a BTD application are in, the data just need to be verified(Principal Investigator) and compiled for BTD application in first quarter of 2023.
Large Pharma partners.
Exemple of two large pharma... Pfizer & Merck. Both Pfizer & Merck have a market cap of approximately 300 billions$(big money).
Sigma-Aldrich Corporation has been manufacturing TLD-1433 PDC since 2014.
Sigma-Aldrich Corporation is owned by MERCK.
All the above could start a nice bidding war for TLT treatment.
The more you dig for info on TLT treatment the more you like your TLT shares."
Agree...any future partner currently wants to corner both the intermediate & high-risk NMIBC markets. If/when TLT receives an AA, there would be no easier/better way to kick Merck to the curb for the above indications than to partner with someone like TLT.
For a high-risk NMIBC patient who responds to induction (6 treatments), it is recommended by AUA that he continue maintenance BCG for 3 years as tolerated....that's a total of 33 treatments (including induction) by my count. Even for an intermediate-risk NMIBC patient who responds to BCG induction, it is still recommended that a provider consider maintenance BCG for 1 year...a total of 15 treatments. Considering the above number of treatments required, the ongoing BCG shortage, BCG's suboptimal efficacy rate for higher-risk NMIBC, & for those who are intolerant to BCG, a one or two-dose treatment option seems like a no-brainer.
Merck has long been the experienced/go-to source for treating higher-risk NMIBC, & considering BCG isn't easy nor that cost-effective to manufacture (reason why Merck is the only producer...there's little incentive/profit motive), it would make sense from both an economic & altruistic sense for Merck to entice the right partner in order to maintain control of this highly unmet market. Combining &/or transitioning its current tech to a much more efficient/effective/versatile approach (TLT's) shouldn't be too bitter of a pill to swallow when you consider TLT's massive potential across multiple indications.
Though this trial strictly addresses only high-risk NMIBC (with CIS disease), I included content re: intermediate-risk NMIBC simply to illustrate the treatment "possibilities" our ACT could potentially provide to not only CIS patients, but to also the largest risk group among NMIBC patients (intermediate-risk). The incredible potential of our ACT to address earlier stages of bladder cancer seemed to be the spirit/theme of Wildbird1' s comments....my comments were simply in keeping/agreement with his. Of course, a proper clinical trial would be needed to validate the above potential.
A recent metanalysis in the journal of European Urology Focus (3/2022) emphasized the need for more clear treatment guidelines for this risk group & concluded that incorporating maintenance therapy was a superior protocol in terms of longer-term cancer recurrence. Imo, comparative studies are sorely lacking for this indication & I believe our ACT will be in a good position one day to meet that need. Good luck...