Nice find, mfglola. In addition to vilastobart, an
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Posted On: 11/12/2025 11:44:45 PM
Nice find, mfglola. In addition to vilastobart, another drug called zanzalintinib also had pretty good results in MSS mCRC. And Buddyboy recently noted the CAR-T therapy just licensed by Lyell. So the competition in this space is active... as it should be. But all three have problems that make leronlimab look pretty good. Here's the comparison.
Exelixis' (EXEL) tyrosine-kinase inhibitor "zanza" is claiming to "set a new survival bar" in MSS mCRC as it recently passed a Phase III trial. And 15.9 months OS is impressive in the heavily treated population. But that number comes from a subset of individuals without liver mets. In other words, zanza works much better if you don't have liver metastases. (And yet this is a trial in mCRC... curious). The OS numbers dropped to 10.9 months when patients with liver mets were included... not too far away from the current SOC (10.8 mo). And the ORR--the primary endpoint in our trial--is kinda lame at 4%. So I believe that though they may set a new survival bar... it won't last long.
Safety is also an issue. 59% of patients in the zanza arm got grade 3/4 adverse events compared to 37% of those who got the placebo. Two died in the trial. The kicker, for me, was that 18% of the patients getting the drug dropped out of the study! Not good...
Xilio's (XLO) anti CTLA-4 drug "vila" has a good ORR of 40%, but once again, in patients without liver mets. In their recent poster I couldn't even find Overall Survival numbers, which says to me they aren't great... or the numbers are still maturing, as data does in these trials. Vila looks pretty safe, though.
What I get from these two trials is... the drugs don't work very well if you have liver mets. Dealing with metastases seems leronlimab's strength, of course, so we are sitting pretty in that regard. And in these trials, both drugs were paired with a PD-1/PDL-1 inhibitor, which wasn't the case for mCRC patients in the basket trial. So even without an ICI, leronlimab mono-therapy bests or compares favorably to either of these drug combinations (60% ORR, 15.4 months mOS; small sample numbers, of course).
These numbers make me curious about what numbers leronlimab is going to achieve in primary tumors without liver mets. If they are not great I could see a triple combo with LL, vila, and a PDL-1 inhibitor; no chemo, good safety. But our numbers, paired with, say, Keytruda or Tecentriq, should be awesome, if the Ladies tell us anything...
The CAR-T therapy from Lyell looks very promising in terms of efficacy--60% ORR... But horrible when it comes to cost and safety. (For those who aren't aware, CAR-T therapy involves taking T cells from the body, engineering them to fight cancer, and culturing enough to provide a therapeutic dosage when returned to the body). No off-the-shelf therapy here, with lots of patient-monitoring necessary in the hospital setting. And thus the $355,000-plus price tag you've probably seen)...
Turns out if any of these CAR-T therapies work out, leronlimab will probably be given to patients to quell the Cytokine Storm... and we will make out either way. So why not just use LL on the cancer to begin with?
Check out this from a recent PR from Lyell: "When it comes to safety, 5 of the 6 patients who received the higher dose experienced cytokine release syndrome--a common side effect of CAR-Ts--and diarrhea. One of the patients "experienced a dose-limiting toxicity," including grade 3 diarrhea, grade 4 inflammation of the intestine and then "death from fungal sepsis 48 days post-infusion." Yikes! Death as the dose-limiting toxicity...
We all wait for numbers from our mCRC trial... but these three competitors all have serious weaknesses in comparison to leronlimab. Metastatic CRC is a really tough indication! But even as a mono-therapy we might very well be Best-In-Class--because we kick RANTES ass! Paired with an ICI... I figure we'll make some history.
Exelixis' (EXEL) tyrosine-kinase inhibitor "zanza" is claiming to "set a new survival bar" in MSS mCRC as it recently passed a Phase III trial. And 15.9 months OS is impressive in the heavily treated population. But that number comes from a subset of individuals without liver mets. In other words, zanza works much better if you don't have liver metastases. (And yet this is a trial in mCRC... curious). The OS numbers dropped to 10.9 months when patients with liver mets were included... not too far away from the current SOC (10.8 mo). And the ORR--the primary endpoint in our trial--is kinda lame at 4%. So I believe that though they may set a new survival bar... it won't last long.
Safety is also an issue. 59% of patients in the zanza arm got grade 3/4 adverse events compared to 37% of those who got the placebo. Two died in the trial. The kicker, for me, was that 18% of the patients getting the drug dropped out of the study! Not good...
Xilio's (XLO) anti CTLA-4 drug "vila" has a good ORR of 40%, but once again, in patients without liver mets. In their recent poster I couldn't even find Overall Survival numbers, which says to me they aren't great... or the numbers are still maturing, as data does in these trials. Vila looks pretty safe, though.
What I get from these two trials is... the drugs don't work very well if you have liver mets. Dealing with metastases seems leronlimab's strength, of course, so we are sitting pretty in that regard. And in these trials, both drugs were paired with a PD-1/PDL-1 inhibitor, which wasn't the case for mCRC patients in the basket trial. So even without an ICI, leronlimab mono-therapy bests or compares favorably to either of these drug combinations (60% ORR, 15.4 months mOS; small sample numbers, of course).
These numbers make me curious about what numbers leronlimab is going to achieve in primary tumors without liver mets. If they are not great I could see a triple combo with LL, vila, and a PDL-1 inhibitor; no chemo, good safety. But our numbers, paired with, say, Keytruda or Tecentriq, should be awesome, if the Ladies tell us anything...
The CAR-T therapy from Lyell looks very promising in terms of efficacy--60% ORR... But horrible when it comes to cost and safety. (For those who aren't aware, CAR-T therapy involves taking T cells from the body, engineering them to fight cancer, and culturing enough to provide a therapeutic dosage when returned to the body). No off-the-shelf therapy here, with lots of patient-monitoring necessary in the hospital setting. And thus the $355,000-plus price tag you've probably seen)...
Turns out if any of these CAR-T therapies work out, leronlimab will probably be given to patients to quell the Cytokine Storm... and we will make out either way. So why not just use LL on the cancer to begin with?
Check out this from a recent PR from Lyell: "When it comes to safety, 5 of the 6 patients who received the higher dose experienced cytokine release syndrome--a common side effect of CAR-Ts--and diarrhea. One of the patients "experienced a dose-limiting toxicity," including grade 3 diarrhea, grade 4 inflammation of the intestine and then "death from fungal sepsis 48 days post-infusion." Yikes! Death as the dose-limiting toxicity...
We all wait for numbers from our mCRC trial... but these three competitors all have serious weaknesses in comparison to leronlimab. Metastatic CRC is a really tough indication! But even as a mono-therapy we might very well be Best-In-Class--because we kick RANTES ass! Paired with an ICI... I figure we'll make some history.
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