I did enjoy the movie, thank you. We many need to
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Posted On: 12/20/2019 6:49:57 PM
I did enjoy the movie, thank you. We many need to remove "cliff notes", but that is okay. I believe I included everyones suggestion. Those ideas also sparked some more of my own. Still a work in progress. I need to add link we have created. Some are stickied, some like ohm's huge list he posted, I need to search for his post on the indications he gave before
If you see anything else, typos, fixes, let me know. I think next week will be slow and I will be on vacation after Christmas. So I plan on having this finished first week in January.
CytoDyn Cliff Notes
Drug in clinical development: Leronlimab(Pro 140)
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 in including governing DNA damage repair, repolarization of tumor-associated macrophages, promotes leukocyte (and metastatic cancer ccr5+ cells) trafficking to the brain, bones, liver and lungs.
What makes it special from than other ccr5 antagonists?
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 vs allosteric in small molecule which enables resistance development in all small molecule antagonists.
Longer half-life: weekly dosing vs daily with others
Safety: No serious side effects or serious adverse events in over 830 patients. This makes leronlimab unique among many HIV and cancer drugs. This has also allowed phase 1 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. 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.
Science Advisors: Dr Sacha/OHSU, Dr. Patterson/IncellDx, Dr. Lindner/ Cleveland Clinic, Dr. Dennis Burger/ex-CSO CYDY, also CEO of several nasdaq bio, Dr. Maddon (inventor or leronlimab and discovered CD4/HIV connection)
Clinical Advisors: Dr Dhody/Amarex Clinical Research, Dr Dolezal/Pacific Hematoloty, Dr. Lalezari/Quest Clinical Research
Manufacturing: AGC & Samsung Biologics (mAb global leader which approved deal with no upfront payment)
HIV:
Combo: Unmet Need R5 Population. Fast Track Designation, Completed Phase3 with BLA submission December/January, BLA rolling review
Mono: R5 Population suppressed V.: In Phase 2b/3 investigatory trial. Phase 3 pivotal could start 2020 with FDA approval,
5 patients on mono five years with no drug resistance; over 150 patients on mono for over 1 year
PrEP: Coordinating with Thai Red Cross/Dr Sacha funding for 1200 patient study, one arm monthly dosing
Potential partner US Army, talks with US Senators with funding, first goal BTD submission
Licensing: Vyera US/HIV only, 50% net sales & 87M milestone. Other global and US non-HIV still open.
FDA denied ODD stating population larger than 200k is a possibility
Cancer
Animal: 98% metastatic tumor burden reduction in tnbc mice model
mTNBC— Fast Track Designation: Phase 1b/2: Patient 1 CTC reduced to zero in first eight weeks, matching similar results in animal model. Enrolling next two soon. Will Apply for BTD if similar results
Colon—Phase 2 approval, 30 patient with Regorafenib, enrollment not started
Compassionate use approved: melanoma, pancreatic, lung, liver, breast, and prostate
Basket trial with in works with melanoma, pancreatic, lung, liver, breast, and prostate
NASH
Animal: inhibited lipid uptake, liver fibrosis, and fatty liver development
Phase 2 approval, 60 patients, random, double blind-enrollment not started
Brenden Rae, “ we expect there to be a significant interest from industry stakeholders in the development of leronlimab for the treatment of NASH.”
GvHD: Orphan Drug Designation
Animal: 100% survival with leronlimab vs 0 without
Phase 2 approval 60 patient, enrollment not started
Multiple Sclerosis
P2 protocol already finalized by Dr. Denis Burger following same structure of Biogen's Tysabri. IND submission early 2020
Possible other ccr5 connections:
Stroke, COPD, Alzheimer's Disease, Atherosclerosis, Diabetes, HCV, Inflammatory Bowel, Pulmonary Diseases
Links to leronlimab papers?
Links to CCR5
Links to Cancer MOA
Link to Cancer Papers
If you see anything else, typos, fixes, let me know. I think next week will be slow and I will be on vacation after Christmas. So I plan on having this finished first week in January.
CytoDyn Cliff Notes
Drug in clinical development: Leronlimab(Pro 140)
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 in including governing DNA damage repair, repolarization of tumor-associated macrophages, promotes leukocyte (and metastatic cancer ccr5+ cells) trafficking to the brain, bones, liver and lungs.
What makes it special from than other ccr5 antagonists?
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 vs allosteric in small molecule which enables resistance development in all small molecule antagonists.
Longer half-life: weekly dosing vs daily with others
Safety: No serious side effects or serious adverse events in over 830 patients. This makes leronlimab unique among many HIV and cancer drugs. This has also allowed phase 1 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. 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.
Science Advisors: Dr Sacha/OHSU, Dr. Patterson/IncellDx, Dr. Lindner/ Cleveland Clinic, Dr. Dennis Burger/ex-CSO CYDY, also CEO of several nasdaq bio, Dr. Maddon (inventor or leronlimab and discovered CD4/HIV connection)
Clinical Advisors: Dr Dhody/Amarex Clinical Research, Dr Dolezal/Pacific Hematoloty, Dr. Lalezari/Quest Clinical Research
Manufacturing: AGC & Samsung Biologics (mAb global leader which approved deal with no upfront payment)
HIV:
Combo: Unmet Need R5 Population. Fast Track Designation, Completed Phase3 with BLA submission December/January, BLA rolling review
Mono: R5 Population suppressed V.: In Phase 2b/3 investigatory trial. Phase 3 pivotal could start 2020 with FDA approval,
5 patients on mono five years with no drug resistance; over 150 patients on mono for over 1 year
PrEP: Coordinating with Thai Red Cross/Dr Sacha funding for 1200 patient study, one arm monthly dosing
Potential partner US Army, talks with US Senators with funding, first goal BTD submission
Licensing: Vyera US/HIV only, 50% net sales & 87M milestone. Other global and US non-HIV still open.
FDA denied ODD stating population larger than 200k is a possibility
Cancer
Animal: 98% metastatic tumor burden reduction in tnbc mice model
mTNBC— Fast Track Designation: Phase 1b/2: Patient 1 CTC reduced to zero in first eight weeks, matching similar results in animal model. Enrolling next two soon. Will Apply for BTD if similar results
Colon—Phase 2 approval, 30 patient with Regorafenib, enrollment not started
Compassionate use approved: melanoma, pancreatic, lung, liver, breast, and prostate
Basket trial with in works with melanoma, pancreatic, lung, liver, breast, and prostate
NASH
Animal: inhibited lipid uptake, liver fibrosis, and fatty liver development
Phase 2 approval, 60 patients, random, double blind-enrollment not started
Brenden Rae, “ we expect there to be a significant interest from industry stakeholders in the development of leronlimab for the treatment of NASH.”
GvHD: Orphan Drug Designation
Animal: 100% survival with leronlimab vs 0 without
Phase 2 approval 60 patient, enrollment not started
Multiple Sclerosis
P2 protocol already finalized by Dr. Denis Burger following same structure of Biogen's Tysabri. IND submission early 2020
Possible other ccr5 connections:
Stroke, COPD, Alzheimer's Disease, Atherosclerosis, Diabetes, HCV, Inflammatory Bowel, Pulmonary Diseases
Links to leronlimab papers?
Links to CCR5
Links to Cancer MOA
Link to Cancer Papers
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