twinter, three good questions and one case of mistaken identity worth gently clearing up.
On CCR2 blockade side effects: the published clinical data from TAK-202, which is a selective CCR2 inhibitor tested across five clinical studies, shows a generally mild profile. The most common expected events in subjects treated with TAK-202 include rash, headache, influenza-like illness, and mild reductions in blood monocyte count, which were stable during dosing and returned to normal after discontinuation. There has been no evidence of serious infections or cell depletion, and no maximum tolerated dose was defined due to the absence of dose-limiting toxicities.
The monocyte count reduction makes sense: CCR2 governs monocyte egress from bone marrow into circulation, so blocking it temporarily reduces circulating monocyte levels without depleting the bone marrow reservoir. The skin rash noted in a small number of TAK-202 subjects led to discontinuation in two patients, but this was not a dominant or severe safety signal across the broader study population.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008242/
On Ben Sasse: the skin problems he described publicly were not from leronlimab or CCR2 blockade. Sasse is taking daraxonrasib from Revolution Medicines for pancreatic cancer in a clinical trial at MD Anderson, and the nasty skin rash, peeling, and bleeding he described is a known side effect of that RAS inhibitor, similar in appearance to severe psoriasis. A different drug, a different mechanism, a different target entirely. The confusion is understandable given that his case has been discussed in the community, but the skin toxicity belongs to daraxonrasib's EGFR-adjacent mechanism, not to anything in the CCR5 or CCR2 pharmacology .
https://www.clinicalleader.com/doc/cytodyn-fd...ancer-0001
On whether a highly successful leronlimab outcome would slow future cancer research funding: this is the most interesting question you have asked in this thread and the answer is certainly the opposite of what the concern implies.
The history of major therapeutic breakthroughs in oncology consistently shows that genuine paradigm shifts accelerate research rather than decelerate it. When imatinib produced near-complete responses in CML, it did not end research into leukemia. It generated an entirely new field of kinase inhibitor biology which funded a decade of subsequent drug development across multiple cancer types. When the first ICI responses were documented in melanoma, the research apparatus did not conclude the problem was solved. It spawned a thousand combination studies, biomarker programs, and next-generation checkpoint inhibitor programs that are still running today.
A confirmed leronlimab ORR in MSS mCRC would not answer the cancer research question. It would reframe it entirely. Every laboratory studying cold tumor resistance would immediately want to understand which patients responded, why the responders responded, what the non-responders' tumors were doing differently, whether CCR2 co-blockade extends the benefit, which alternative checkpoints emerge after durable CCR5 blockade, and how the mechanism translates into first-line rather than salvage settings. The confirmed result creates more funded questions than it closes.
The research apparatus follows the signal. A strong enough signal does not turn the lights off. It turns them all on at once.
Now go enjoy the wait. October is closer than it was yesterday.
On CCR2 blockade side effects: the published clinical data from TAK-202, which is a selective CCR2 inhibitor tested across five clinical studies, shows a generally mild profile. The most common expected events in subjects treated with TAK-202 include rash, headache, influenza-like illness, and mild reductions in blood monocyte count, which were stable during dosing and returned to normal after discontinuation. There has been no evidence of serious infections or cell depletion, and no maximum tolerated dose was defined due to the absence of dose-limiting toxicities.
The monocyte count reduction makes sense: CCR2 governs monocyte egress from bone marrow into circulation, so blocking it temporarily reduces circulating monocyte levels without depleting the bone marrow reservoir. The skin rash noted in a small number of TAK-202 subjects led to discontinuation in two patients, but this was not a dominant or severe safety signal across the broader study population.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008242/
On Ben Sasse: the skin problems he described publicly were not from leronlimab or CCR2 blockade. Sasse is taking daraxonrasib from Revolution Medicines for pancreatic cancer in a clinical trial at MD Anderson, and the nasty skin rash, peeling, and bleeding he described is a known side effect of that RAS inhibitor, similar in appearance to severe psoriasis. A different drug, a different mechanism, a different target entirely. The confusion is understandable given that his case has been discussed in the community, but the skin toxicity belongs to daraxonrasib's EGFR-adjacent mechanism, not to anything in the CCR5 or CCR2 pharmacology .
https://www.clinicalleader.com/doc/cytodyn-fd...ancer-0001
On whether a highly successful leronlimab outcome would slow future cancer research funding: this is the most interesting question you have asked in this thread and the answer is certainly the opposite of what the concern implies.
The history of major therapeutic breakthroughs in oncology consistently shows that genuine paradigm shifts accelerate research rather than decelerate it. When imatinib produced near-complete responses in CML, it did not end research into leukemia. It generated an entirely new field of kinase inhibitor biology which funded a decade of subsequent drug development across multiple cancer types. When the first ICI responses were documented in melanoma, the research apparatus did not conclude the problem was solved. It spawned a thousand combination studies, biomarker programs, and next-generation checkpoint inhibitor programs that are still running today.
A confirmed leronlimab ORR in MSS mCRC would not answer the cancer research question. It would reframe it entirely. Every laboratory studying cold tumor resistance would immediately want to understand which patients responded, why the responders responded, what the non-responders' tumors were doing differently, whether CCR2 co-blockade extends the benefit, which alternative checkpoints emerge after durable CCR5 blockade, and how the mechanism translates into first-line rather than salvage settings. The confirmed result creates more funded questions than it closes.
The research apparatus follows the signal. A strong enough signal does not turn the lights off. It turns them all on at once.
Now go enjoy the wait. October is closer than it was yesterday.
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