Results:
Adverse Events (Safety):
They won't copy/paste, but this what the graph lists, & in this order:
* vascular disorders
*skin & subcutaneous tissue disorders
*respitory, thoracic & mediastonial disorders
*renial & urinary disorders
*nervous system disorders
*metabolism & nutrition disorders
*investigations
*injury, posioning & procedural complications
*general disorders & administration site conditions
*gastrointestinal disorders
*eye disorders
*endocrine disorders
*blood & lymphatic disorders
** the graph shows Placebo, 350mg, 700mg & 700mg Haplotype
Serum Chemistry and Labs:
I can't type out all the data in each section, it's small & alot.
These are the catogories in order as listed:
*chemistry
*ck-8
*fibro test
*lipids
*serum pro-inflammatory assessment
CONCLUSIONS
RESULTS
ACKNOWLEDGEMENTS
CytoDyn Inc. is very grateful to all study participants for taking part in this study and for making this research
possible. In addition, we thank all the clinical sites and their staff for facilitating what we hope will be become a viable treatment solution for those afflicted with NASH.
We would also like to thank the following people for their invaluable contributions and help with undertaking components to make this study happen: William Sanchez, Rizwana Mohseni, Shilipi Mittal, Reem Ghalib, Eva-Maria Heurich, Antonio Terrelonge, Hernan Salazar, Joseph Meidling, Wendy Walton, and Antonio Migliarese.
Contact: For inquiries regarding leronlimab, our science, or our new developments, please send us and email to info@cytodyn.com.
AIM
REFERENCES
1. Lefere S, Puengel T, Hundertmark J, Penners C, Frank AK, Guillot A, de Muynck K, Heymann F, Adarbes V,
Defrêne E, Estivalet C, Geerts A, Devisscher L, Wettstein G, Tacke F. Differential effects of selective- and pan-PPAR agonists on experimental steatohepatitis and hepatic macrophages. J Hepatol. 2020 Oct;73(4):757-770. doi: 10.1016/j.jhep.2020.04.025. Epub 2020 Apr 29. PMID: 32360434.
2. Lefebvre E, M. G. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis. 2016; 11(6), e0158156.
METHOD
Subjects who meet all eligibility criteria, as per data gathered from the screening period qualify for
enrollment. All subjects who fail to meet eligibility criteria will be considered screen failure and exit
the study without further evaluation. The study consisted of two parts:
• Part 1 of the study, eligible subjects randomized to 1:1 to one of the two study arms to receive
leronlimab 700 mg (Group A), or placebo (Group
given once per week (±1 day) at the study
site for up to 13 weeks during the treatment period (with up to 60 participants).
• Leronlimab 700 mg SC weekly injection (Group A)
• Placebo SC weekly injection (Group
• Part 2 of the study, eligible subjects enrolled to receive leronlimab 350 mg open label given
one per week (±1 day) at the study site for up to 13 weeks during the treatment period (with up
to 28 participants).
• Leronlimab 350 mg SC weekly injection
Primary efficacy objective:
Change from baseline in hepatic fat fraction, assessed by magnetic resonance imaging-derived
proton density fat fraction (MRI-PDFF) at week 14.
Secondary efficacy objective:
Change from baseline in fibro-inflammatory activity in the liver as assessed by cT1 (corrected T1)
at week 14. cT1 is obtained by multiparametric magnetic resonance imaging of the liver and is a
quantitative metric for assessing a composite of liver inflammation and fibrosis, expressed in
milliseconds (msec). Additional objectives were change from baseline in LFT, chemokine and
cytokine levels and key biomarkers of inflammation to week 14.
A. Fatty deposits in NSG mice fed High Fat, High Cholesterol diet. Images show frozen section stained with Oil Red O were scanned at 20X and digitized using Aperio AT2 slide scanner (Leica Biosystems, and analyzed using QuPath v0.2.01 imaging software). B. Comparison of Hepatic Steatosis in leronlimab vs. IgG-treated NSG mice fed a high fat, high cholesterol diet.
Graph shows mean Oil red O positive pixels, relative to entire region of interest (ROI) and standard error (SE) were calculated for both treatment groups. Percent positivity in IgG treated group was 9.751 ± 1.789. Percent positivity in leronlimab treated group was 3.207 ±1.515. Student’s t test p=0.014. Steatosis wasnumerically scored following semi-quantitative pathological standard.
A. B.
• All analyses performed were exploratory.
• Treatment with leronlimab was generally well tolerated in both Part 1 and Part 2.
Part 1
• Leronlimab 700 mg did not reduce mean change in PDFF and cT1 from baseline to week 14 vs.
placebo.
Part 2
• Leronlimab 350 mg significantly reduced mean change in PDFF and cT1 from baseline to week
14 vs. placebo.
• Despite increased fibro-inflammation, in patients with moderate and severe cT1 values at
baseline, leronlimab 350 mg still showed significantly reduced cT1 from baseline to week 14 vs.
placebo.
Part 1 & Part 2 pooled
• Pooled 350 mg + 700 mg group also had significant reductions in PDFF and cT1 vs. placebo.
• Although small sample size (n=5) CCR5 haplotype analysis is suggestive that specific-haplotypes may be better suited for the 700 mg dose of leronlimab.
• The CCR5 promoter region has been shown to play a critical role in CCR5 transcriptional regulation of disease progression for HIV, HBV, Chagas, heart disease and cancer.
• CCR5 transcriptional activity, disease progression can be slowed or accelerated.
• Based on these data, we hypothesized that not only does surface CCR5 expression level likely play a part in NASH disease progression, but CCR5 specific haplotypes would correlate with dose and treatment outcomes.
Serum analysis:
• Reductions in ALT, AST and Alkaline Phosphatase were observed in the 350 mg group and cT1 subgroups vs placebo with corresponding reductions in VCAM, CCL2, CCL3, CCL5, CCL18, INF gamma, IL-6, IL-8, IL-1 Receptor Antagonist (IL-1RA), TNF Receptor 2,
Tissue Inhibitor of MMP-1 and EN RAGE.
• The mechanism of action for leronlimab appears to be multifactorial involving VCAM, CCL2, CCL3, CCL11, and CCL18 in addition to competitive binding of CCR5 effecting metabolic and fibro-inflammatory parameters.
• The mechanism of action for leronlimab appears to be multifactorial involving VCAM, CCL2, CCL3, CCL11, and CCL18 in addition to competitive binding of CCR5 effecting metabolic and fibro-inflammatory parameters
_______________
That's all.....anything i misspelled is due to i don't use pre-text....lol !
Adverse Events (Safety):
They won't copy/paste, but this what the graph lists, & in this order:
* vascular disorders
*skin & subcutaneous tissue disorders
*respitory, thoracic & mediastonial disorders
*renial & urinary disorders
*nervous system disorders
*metabolism & nutrition disorders
*investigations
*injury, posioning & procedural complications
*general disorders & administration site conditions
*gastrointestinal disorders
*eye disorders
*endocrine disorders
*blood & lymphatic disorders
** the graph shows Placebo, 350mg, 700mg & 700mg Haplotype
Serum Chemistry and Labs:
I can't type out all the data in each section, it's small & alot.
These are the catogories in order as listed:
*chemistry
*ck-8
*fibro test
*lipids
*serum pro-inflammatory assessment
CONCLUSIONS
RESULTS
ACKNOWLEDGEMENTS
CytoDyn Inc. is very grateful to all study participants for taking part in this study and for making this research
possible. In addition, we thank all the clinical sites and their staff for facilitating what we hope will be become a viable treatment solution for those afflicted with NASH.
We would also like to thank the following people for their invaluable contributions and help with undertaking components to make this study happen: William Sanchez, Rizwana Mohseni, Shilipi Mittal, Reem Ghalib, Eva-Maria Heurich, Antonio Terrelonge, Hernan Salazar, Joseph Meidling, Wendy Walton, and Antonio Migliarese.
Contact: For inquiries regarding leronlimab, our science, or our new developments, please send us and email to info@cytodyn.com.
AIM
REFERENCES
1. Lefere S, Puengel T, Hundertmark J, Penners C, Frank AK, Guillot A, de Muynck K, Heymann F, Adarbes V,
Defrêne E, Estivalet C, Geerts A, Devisscher L, Wettstein G, Tacke F. Differential effects of selective- and pan-PPAR agonists on experimental steatohepatitis and hepatic macrophages. J Hepatol. 2020 Oct;73(4):757-770. doi: 10.1016/j.jhep.2020.04.025. Epub 2020 Apr 29. PMID: 32360434.
2. Lefebvre E, M. G. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis. 2016; 11(6), e0158156.
METHOD
Subjects who meet all eligibility criteria, as per data gathered from the screening period qualify for
enrollment. All subjects who fail to meet eligibility criteria will be considered screen failure and exit
the study without further evaluation. The study consisted of two parts:
• Part 1 of the study, eligible subjects randomized to 1:1 to one of the two study arms to receive
leronlimab 700 mg (Group A), or placebo (Group
given once per week (±1 day) at the study site for up to 13 weeks during the treatment period (with up to 60 participants).
• Leronlimab 700 mg SC weekly injection (Group A)
• Placebo SC weekly injection (Group
• Part 2 of the study, eligible subjects enrolled to receive leronlimab 350 mg open label given
one per week (±1 day) at the study site for up to 13 weeks during the treatment period (with up
to 28 participants).
• Leronlimab 350 mg SC weekly injection
Primary efficacy objective:
Change from baseline in hepatic fat fraction, assessed by magnetic resonance imaging-derived
proton density fat fraction (MRI-PDFF) at week 14.
Secondary efficacy objective:
Change from baseline in fibro-inflammatory activity in the liver as assessed by cT1 (corrected T1)
at week 14. cT1 is obtained by multiparametric magnetic resonance imaging of the liver and is a
quantitative metric for assessing a composite of liver inflammation and fibrosis, expressed in
milliseconds (msec). Additional objectives were change from baseline in LFT, chemokine and
cytokine levels and key biomarkers of inflammation to week 14.
A. Fatty deposits in NSG mice fed High Fat, High Cholesterol diet. Images show frozen section stained with Oil Red O were scanned at 20X and digitized using Aperio AT2 slide scanner (Leica Biosystems, and analyzed using QuPath v0.2.01 imaging software). B. Comparison of Hepatic Steatosis in leronlimab vs. IgG-treated NSG mice fed a high fat, high cholesterol diet.
Graph shows mean Oil red O positive pixels, relative to entire region of interest (ROI) and standard error (SE) were calculated for both treatment groups. Percent positivity in IgG treated group was 9.751 ± 1.789. Percent positivity in leronlimab treated group was 3.207 ±1.515. Student’s t test p=0.014. Steatosis wasnumerically scored following semi-quantitative pathological standard.
A. B.
• All analyses performed were exploratory.
• Treatment with leronlimab was generally well tolerated in both Part 1 and Part 2.
Part 1
• Leronlimab 700 mg did not reduce mean change in PDFF and cT1 from baseline to week 14 vs.
placebo.
Part 2
• Leronlimab 350 mg significantly reduced mean change in PDFF and cT1 from baseline to week
14 vs. placebo.
• Despite increased fibro-inflammation, in patients with moderate and severe cT1 values at
baseline, leronlimab 350 mg still showed significantly reduced cT1 from baseline to week 14 vs.
placebo.
Part 1 & Part 2 pooled
• Pooled 350 mg + 700 mg group also had significant reductions in PDFF and cT1 vs. placebo.
• Although small sample size (n=5) CCR5 haplotype analysis is suggestive that specific-haplotypes may be better suited for the 700 mg dose of leronlimab.
• The CCR5 promoter region has been shown to play a critical role in CCR5 transcriptional regulation of disease progression for HIV, HBV, Chagas, heart disease and cancer.
• CCR5 transcriptional activity, disease progression can be slowed or accelerated.
• Based on these data, we hypothesized that not only does surface CCR5 expression level likely play a part in NASH disease progression, but CCR5 specific haplotypes would correlate with dose and treatment outcomes.
Serum analysis:
• Reductions in ALT, AST and Alkaline Phosphatase were observed in the 350 mg group and cT1 subgroups vs placebo with corresponding reductions in VCAM, CCL2, CCL3, CCL5, CCL18, INF gamma, IL-6, IL-8, IL-1 Receptor Antagonist (IL-1RA), TNF Receptor 2,
Tissue Inhibitor of MMP-1 and EN RAGE.
• The mechanism of action for leronlimab appears to be multifactorial involving VCAM, CCL2, CCL3, CCL11, and CCL18 in addition to competitive binding of CCR5 effecting metabolic and fibro-inflammatory parameters.
• The mechanism of action for leronlimab appears to be multifactorial involving VCAM, CCL2, CCL3, CCL11, and CCL18 in addition to competitive binding of CCR5 effecting metabolic and fibro-inflammatory parameters
_______________
That's all.....anything i misspelled is due to i don't use pre-text....lol !
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