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Recently @4dpharmaplc #DDDD $LBPS released a Form F-1 as a registration statement for certain foreign private issuers.
There were a few interesting snippets there, mostly related to MRx0518.
A thread.
https://sec.report/Document/0001493152-21-009577/
There were a few interesting snippets there, mostly related to MRx0518.
A thread.
https://sec.report/Document/0001493152-21-009577/
1/
4D released this graph of tumour growth for the patients on the MRx0518/Keytruda trial.
A reminder that this is a highly refractory/late stage cancer cohort, that had not seen disease control through as many as 7 different treatment options prior to the trial.
4D released this graph of tumour growth for the patients on the MRx0518/Keytruda trial.
A reminder that this is a highly refractory/late stage cancer cohort, that had not seen disease control through as many as 7 different treatment options prior to the trial.
2/
Stable disease is defined as tumour growth up to 20%.
A partial response is defined as tumour reduction of at least 50%.
A complete response is self-explanatory.
All three combined represent disease control rate (DCR).
Stable disease is defined as tumour growth up to 20%.
A partial response is defined as tumour reduction of at least 50%.
A complete response is self-explanatory.
All three combined represent disease control rate (DCR).
3/
The last two combined represent overall response rate (ORR).
Merck and 4D set a pre-defined threshold of 10% on the disease control rate to class this trial as a 'success'.
The last two combined represent overall response rate (ORR).
Merck and 4D set a pre-defined threshold of 10% on the disease control rate to class this trial as a 'success'.
4/
You may be wondering why there are only 10 lines on the graph above if the cohort was 12 patients.
This is because for 2 patients who were withdrawn due to side effects from tumour progression, there was no radiological assessment possible.
You may be wondering why there are only 10 lines on the graph above if the cohort was 12 patients.
This is because for 2 patients who were withdrawn due to side effects from tumour progression, there was no radiological assessment possible.
5/
From F-1:
'Of the 12 patients enrolled in Part A of the combination trial, seven patients were evaluated at the first scheduled restaging scan at nine weeks, and five were withdrawn prior to the first scheduled restaging scan due to clinical evidence of disease progression.'
From F-1:
'Of the 12 patients enrolled in Part A of the combination trial, seven patients were evaluated at the first scheduled restaging scan at nine weeks, and five were withdrawn prior to the first scheduled restaging scan due to clinical evidence of disease progression.'
6/
Withdrawal prior to the first 9 week checkpoint does not leave much room for clinical benefit (or lack of it) to be seen. However such is the condition of this treatment group.
We allow for the possibility that the withdrawals are because of the 0518/Keytruda combo (or not!)
Withdrawal prior to the first 9 week checkpoint does not leave much room for clinical benefit (or lack of it) to be seen. However such is the condition of this treatment group.
We allow for the possibility that the withdrawals are because of the 0518/Keytruda combo (or not!)
7/
Looking at the graph above, taking into account ONLY the ones who have continued (and the one who discounted after 2 years, the max. length of the trial):
We have 2 patients on stable disease (assuming the patient with 25% tumour reduction is 'stable disease').
Looking at the graph above, taking into account ONLY the ones who have continued (and the one who discounted after 2 years, the max. length of the trial):
We have 2 patients on stable disease (assuming the patient with 25% tumour reduction is 'stable disease').
8/
We have 2 patients with a partial response, both with ~60% tumour reduction.
So 4 in total with 'disease controlled', including 2 'overall responders'.
What is the 'true' DCR/ORR? A bit of a hairy question. The interval they lie within is as follows:
We have 2 patients with a partial response, both with ~60% tumour reduction.
So 4 in total with 'disease controlled', including 2 'overall responders'.
What is the 'true' DCR/ORR? A bit of a hairy question. The interval they lie within is as follows:
9/
Assuming all 5 withdrawals due to progression were because of the combo therapy:
DCR = 4/12 = 33.3%
ORR = 2/12 = 16.7%
Assuming all 5 withdrawals due to progression were because of the combo therapy:
DCR = 4/12 = 33.3%
ORR = 2/12 = 16.7%
10/
Assuming none of the withdrawals due to progression were because of the combo therapy:
DCR = 4/(12-5) = 57.1%
ORR = 2/(12-5) = 28.6%
So a reasonable estimate of 'true' DCR/ORR is the midpoint of these at 45.2%/22.7%.
In any case far exceeding the predefined 10% threshold.
Assuming none of the withdrawals due to progression were because of the combo therapy:
DCR = 4/(12-5) = 57.1%
ORR = 2/(12-5) = 28.6%
So a reasonable estimate of 'true' DCR/ORR is the midpoint of these at 45.2%/22.7%.
In any case far exceeding the predefined 10% threshold.
11/
Very encouraging and in itself meriting a far higher valuation than we have at present, given the response rate in late stage patients, with a disease encompassing a total addressable market in the tens if not hundreds of £bns.
Very encouraging and in itself meriting a far higher valuation than we have at present, given the response rate in late stage patients, with a disease encompassing a total addressable market in the tens if not hundreds of £bns.
12/
If you want more information on MRx0518 please check my article on 4D which I will link at the bottom of this thread.
If you want more information on MRx0518 please check my article on 4D which I will link at the bottom of this thread.
