My take on the investor’s conference in bullets (this is what was remarkable and/or unclear/uncomplete to me), maybe not the same for many of the much more knowledgeable members in this board:
13 of the 19 patients included in the ctDNA “cascade” chart were treated with 350-milligram dose. This is highly encouraging as a median of 70% reduction in ctDNA might have been achieved with a sub-standard dosage AND that 3 of those 4 patients (in follow-up period) who have gone undetectable are being treated with (only) the 350-milligram dose.
Also, 62% enrolled in the CLOVER rial to date have KRAS mutations, (hardest-to-treat patients in oncology) preliminary results, in Jay’s words: “indicate that leronlimab's early biologic activity might also be agnostic to the KRAS mutation.”
The question is, of course, so what ??, well, with 22 patients with RECIST data at week 8, 15 (68%) are demonstrating shrinkage or classify as having stable disease on their scan. So, this is correlating with the circulating tumor decreases being observed. [color=rgb(16, 42, 234)]There is some fire creating the smoke.[/color]
The patient featured in the poster was not carefully picked (I was afraid it was only a “for show” patient), no, this patient was in the verge of net being in this word who had the standard double FOLFOX chemotherapy with bevacizumab, followed with FOLFII chemotherapy with bevacizumab. And we get these beautiful pictures of the lesions changing not only in size but in their nature as well!!
It is highly encouraging that we have achieved this remarkable landmark with a 350mg dose: with the 700-milligram we will get quicker rapid declines and more sustained declines in ctDNA.
Regarding the all-important PD-L1 induction, we know there is/was a lower rate of induction in patients who received 350-milligram dose, and then it was almost 90% of patients at the 525 or 700-milligram dose. This is so important that some potential industry partners had asked for the data (by the way, not sure what is the meaning of “industry partners” … BP?). 5 out of 5 patients who upregulated and received a checkpoint inhibitor are alive now 5-plus years later (this in regard to TNBC)!!!
Which lead to EAP program where we will be watching like a hawk PD-L1 numbers. Which, if confirmed, will lead to the prime-pair narrative (with a potential super-huge potential, both, in terms of patient outcomes and profitability for the lucky owner of the molecule). Not to mention the other MOAs of improving secretome environment and immune exhaustion (on their own right important milestones).
Another important point that was stressed is the “low bar” we are working against: The RECIST trial had a meager (not my words) single-digit percentage proportion of patients who got shrinkage beyond 30% that counted as partial response (as RECIST criteria).
Still in the low bar: the Phase III SUNLIGHT trial, actually improved LONSURF (not AVASTIN) alone, with only less than 1% of patients having an overall response rate. Of the 246 patients (of data published in the New England Journal) the median progression-free and overall survival was on the order of 6 and 11 months with only 6% of patients even having a partial response (30% decrease in tumor volume), with no complete responders.
So, we are aiming at, 6% response rate. With the numbers we are obtaining this should be a piece of cake!!!
Finally, the prospect of conversations with the I-SPY network and the beginning of studies in leronlimab in HER2-negative patients with breast cancer and as monotherapy agent in a pre-surgery environment is, on its own, a very exiting perspective (large potential market).
13 of the 19 patients included in the ctDNA “cascade” chart were treated with 350-milligram dose. This is highly encouraging as a median of 70% reduction in ctDNA might have been achieved with a sub-standard dosage AND that 3 of those 4 patients (in follow-up period) who have gone undetectable are being treated with (only) the 350-milligram dose.
Also, 62% enrolled in the CLOVER rial to date have KRAS mutations, (hardest-to-treat patients in oncology) preliminary results, in Jay’s words: “indicate that leronlimab's early biologic activity might also be agnostic to the KRAS mutation.”
The question is, of course, so what ??, well, with 22 patients with RECIST data at week 8, 15 (68%) are demonstrating shrinkage or classify as having stable disease on their scan. So, this is correlating with the circulating tumor decreases being observed. [color=rgb(16, 42, 234)]There is some fire creating the smoke.[/color]
The patient featured in the poster was not carefully picked (I was afraid it was only a “for show” patient), no, this patient was in the verge of net being in this word who had the standard double FOLFOX chemotherapy with bevacizumab, followed with FOLFII chemotherapy with bevacizumab. And we get these beautiful pictures of the lesions changing not only in size but in their nature as well!!
It is highly encouraging that we have achieved this remarkable landmark with a 350mg dose: with the 700-milligram we will get quicker rapid declines and more sustained declines in ctDNA.
Regarding the all-important PD-L1 induction, we know there is/was a lower rate of induction in patients who received 350-milligram dose, and then it was almost 90% of patients at the 525 or 700-milligram dose. This is so important that some potential industry partners had asked for the data (by the way, not sure what is the meaning of “industry partners” … BP?). 5 out of 5 patients who upregulated and received a checkpoint inhibitor are alive now 5-plus years later (this in regard to TNBC)!!!
Which lead to EAP program where we will be watching like a hawk PD-L1 numbers. Which, if confirmed, will lead to the prime-pair narrative (with a potential super-huge potential, both, in terms of patient outcomes and profitability for the lucky owner of the molecule). Not to mention the other MOAs of improving secretome environment and immune exhaustion (on their own right important milestones).
Another important point that was stressed is the “low bar” we are working against: The RECIST trial had a meager (not my words) single-digit percentage proportion of patients who got shrinkage beyond 30% that counted as partial response (as RECIST criteria).
Still in the low bar: the Phase III SUNLIGHT trial, actually improved LONSURF (not AVASTIN) alone, with only less than 1% of patients having an overall response rate. Of the 246 patients (of data published in the New England Journal) the median progression-free and overall survival was on the order of 6 and 11 months with only 6% of patients even having a partial response (30% decrease in tumor volume), with no complete responders.
So, we are aiming at, 6% response rate. With the numbers we are obtaining this should be a piece of cake!!!
Finally, the prospect of conversations with the I-SPY network and the beginning of studies in leronlimab in HER2-negative patients with breast cancer and as monotherapy agent in a pre-surgery environment is, on its own, a very exiting perspective (large potential market).
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