Hi all
The dose escalation of the Vaxinia MAST trial has taken my interest. I have put together some very basic graphs to provide a visual of the increase in dosages. If one were to read about the dose escalations with only text in mind ie. cohort 1, cohort 2, cohort 3 - then it might be easy to imagine the doses increasing in a simple linear fashion. This same thinking could also take place when reading 10^6, 10^7, 10^8, etc. Some may uncritically picture a linear scale as cohorts progress. This thinking is incorrect, and I believe a visual is a great way to understand that doses are in fact increasing
exponentially.
I have graphed the following data. I'm providing my numbers here to ensure I haven't made a mistake. I'm sure someone will correct me if I have.
|
Column 1 |
Column 2 |
Column 3 |
| 0 |
Cohort 1 |
1,000,000 |
10^6 |
| 1 |
Cohort 2 |
10,000,000 |
10^7 |
| 2 |
Cohort 3 |
30,000,000 |
3x10^7 |
| 3 |
Cohort 4 |
100,000,000 |
10^8 |
| 4 |
Cohort 5 |
300,000,000 |
3x10^8 |
| 5 |
Cohort 6 |
1,000,000,000 |
10^9 |
| 6 |
Cohort 7 |
3,000,000,000 |
3x10^9 |
I have graphed up to Cohort 7 as I believe this was included in the recent poster presented as ASCO. This visual representation makes sense when considering Yuman Fong's comments about starting at "teeny tiny doses". Amazingly, I believe the CR in Bile Duct cancer was achieved by a patient in Cohort 2. Patients are now being enrolled in Cohort 5, receiving 30 times the dose which has already produced a CR. This is very exciting. To see Imugene planning ahead for Cohort 6 and 7 also suggests that efficacy is improving with increased dosage, why else would further cohorts be investigated? As
@LHI 14 and
@davybabyk have pointed out, CF33 seems to be extremely safe. Finding the RP2D may well found by seeing a flattening of efficacy rather than the introduction of toxicity - I sure hope so.
A bar graph is another great way to see that we may still be in mid-dose ranges with huge potential to increase. YF did say that he has never seen a drug with a bigger therapeutic window than CF33, and that the larger the window the more likely it is to become human therapy. YF stated he believes CF33 will be human therapy and that it may be the most important vaccine ever created. Powerful words. I agree with
@Jov88, I'm happy to wait to see more extraordinary results as doses escalate as it greatly strengthens our value proposition.
For the last graph I removed Cohort 7 because the scale was so large it was difficult to even see Cohort 2. At 10 million PFU we have achieved a CR and an overall response rate of 86% in GI cancers from early cohorts. We are now dosing at 300 million PFU (30 timers higher) and plan to go to a billion and possibly three billion PFU. Yuman Fong said "we are seeing unequivocal cancer killing" and "the virus is acting in the same way it did in animals, in humans". It thrills me to read
@Watmighthavben and
@Outlander2 state they believe "proof of concept" has been achieved, I feel the same way.
@arcsarx made a really interesting point that jumped out at me - we have such highly astute and innovative people leading our company at the forefront of immuno-oncology, I completely agree that having a cleverly designed trial and a great working relationship with the FDA is highly valuable. Moreso than having a wizz-bang presentation style. That's not to say that we can't have both, and we should, but the value in our company is being driven by the trial data. To hear posters believe the FDA knows the potential of CF33, and are facilitating its development through trial design flexibility (Basket Trial) is extremely exciting.
US Politics 2024
A thought I have been pondering recently - might the US election this year have an impact on the Imugene story? Might Biden want to take credit for a landmark breakthrough in cancer treatments? Might a "cure" be branded as one of his achievements in his first term, justifying another? We are probably at too early a stage for that, but I wonder if the 2024 US presidential campaign might throw up an opportunity for Biden to claim his Cancer Moonshot focus has been a success.
My own thoughts and opinions, not financial advice. DYOR.
Have a great weekend.
(20min delay)