Great Dec info on CYDY- Leronlimab (Pro 140) Cliff Notes
What is it?
Leronlimab is a humanized monoclonal antibody targeted against the CCR5 receptor expressed on sub-population of T cells, macrophages, dendritic, eosinophils, microglia, and several cancers types.
Why so many indications?
CCR5 is a chemokine receptor interacting with CCL3, CCL4, and CCL5 (RANTES). CCL5 has an active role in recruiting leukocytes into inflammatory sites, which leronlimab can block. CCR5 also has many other roles: [8,9]
- governing DNA damage repair,
- repolarization of tumor-associated macrophages,
- promoting leukocytes (and metastatic cancer ccr5+ cells) trafficking to the brain, bones, liver and lungs.
What makes it to stand out from than other ccr5 antagonists, HAART, and cancer drugs ?
Low toxicity: Doesn't block natural activity of ccr5 including no hepatotoxicity causing many others to fail their trial safety metric.
No R5 resistance: Competitive inhibitor blocking direct entry to target a specific site on CCR5 that is utilized by HIV vs allosteric in small molecule, which enables resistance development in all small molecule antagonists. With the highest barrier to resistance so far than any other HIV drug, it could be first monotherapy approved drug for HIV.
Weekly dosing/Adherence : Longer half-life (10-14 days) [11,12] allows weekly dosing vs daily pills with others. A large 2013 survey [6,7] of 19 studies showed the association between adherence and specific AEs associated with ART. The same study showed an association with adherence rate and the number of daily pills, 95% adherence from 47% taking one pill daily to 34% with three pills daily. NNRTI, which has traditionally been given as part of core with ART, needs a very high level of adherence to limit mutations Adherence is the second strongest predictor of progression to AIDS after CD4 count. Weekly dosing offers a tremendous advantage in increasing adherence, specifically those in the unmet need category where typically adherence has been the lowest. Note PrEP study will have one arm with monthly dosing as daily pills is one main reason people at risk have stated they avoided PrEP, longer options are better.
Safety: No serious side effects or serious adverse events in over 830 patients. No discontinuing thus far from AEs in mono p2 trial. This makes leronlimab unique among many HIV and cancer drugs. Recognizing overall's drug’s safety FDA has allowed P1 to be skipped in several new indications. This is also helps reduce the added compounding side-effects when using several drugs with HIV or cancer.
Low drug/drug interactions. Leronlimab is eliminated via a saturable, antigen-mediated clearance process [10]. Many other HIV drugs are metabolized by CYP enzymes enabling drug interactions. For example Maraviroc and Rilpivirine are metabolized by CYP3A4, as are many other drugs.
Special Note: HIV has a positive association with NAFLD and cancer, two indications where leronlimab is in p2, which combined with the above benefits, if approved for all indications would make a extremely compelling synergistic treatment for all R5. See end footnote for more details.
Video: Pro 140: How it Combats HIV
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