CytoDyn Inc. · OTC:CYDY
CytoDyn — Technical Presentation (December 2022)
100 slides from CytoDyn's technical presentation, Dec 7, 2022
Slide 1: CytoDyn – R&D Investor Update December 7, 2022
CytoDyn – R&D Investor 1 Update December 7, 2022
Slide 2: Forward Looking Statements
Forward Looking Statements 2 This presentation contains certain forward-looking statements that involve risks, uncertainties and assumptions that are difficult to predict. Words and expressions reflecting optimism, satisfaction or disappointment with current prospects, as well as words such as "beli
Slide 3: Welcome
Welcome Cyrus Arman, PhD MBA – President 3
Slide 4: Agenda & Scientific Advisory Board Speakers
Agenda & Scientific Advisory Board Speakers 4 Dr. Mazen Noureddin Dr. Stefan Glück Dr. Jonah Sacha Welcome and Introduction Cyrus Arman (President) Company Overview and Background Clinical Development Programs Clinical and Preclinical Data in Prioritized Therapeutic Areas Scientific Advisory Board M
Slide 5: Scientific Advisory Board Speakers
Scientific Advisory Board Speakers 5 Dr. Mazen Noureddin Dr. Stefan Glück Dr. Jonah Sacha Director of the Houston Liver Institute and former founding Director of the Fatty Liver Program at Cedars-Sinai Medical Center Conducted over 40 investigational clinical studies and published over 180 papers on
Slide 6: SAB Disclosures
SAB Disclosures 6 Dr. Mazen Noureddin Advisory Board: Altimmune, BI, BMS, 89BIO, EchoSens, Gilead, CytoDyn, GSK, Merck, Novo Nordisk, OWL, Pfizer, Roche diagnostic and Siemens, Terns and Takeda Principal Investigator for a Drug Study: Allergan, Akero, BMS, Gilead, Galectin, Genfit, Conatus,Corcept,
Slide 7: CytoDyn Company Overview
CytoDyn Company Overview 7
Slide 8: CytoDyn's Mission
CytoDyn’s Mission 8 A focused and disciplined clinical development strategy A value-generating path, resulting in economic returns for our investors A moral obligation to generate therapies to improve people’s lives
Slide 9: CytoDyn Company Overview
CytoDyn Company Overview 9 Headquarters: Vancouver, WA Fulltime Employees: 15 (December 2022) Ticker: CYDY CytoDyn Founded in 2002 HIV Tx clinical program started in 2014 Oncology clinical program started in 2019 Refocused Development Strategy in 2022 Acquired rights to PRO 140 (leronlimab) in 2012
Slide 10: CytoDyn's Board of Directors
CytoDyn’s Board of Directors 10 Stephen M. Simes Ryan Dunlap Tanya Urbach Dr. Karen Brunke Dr. Lishomwa Ndhlovu
Slide 11: Manufacturing Partners and Publications
CytoDyn’s Manufacturing Partners and Publications 11 Manufacturing Partners Recent Conference Abstracts Leronlimab Publications (10+)
Slide 12: CCR5 & Leronlimab
Boronyn CCRS5 & Leronlimab 12
Slide 13: The CCR5/CCL5 Axis & Leronlimab
The CCR5/CCL5 Axis & Leronlimab 13 Agents directed against the CCL5/CCR5 axis have been studied in many therapeutic areas such as inflammation, cancers, viral infections, and immune responses In different conditions, the function of the CCL5/CCR5 axis varies, and has implications for infectious dise
Slide 14: CCR5 Inhibitors – Competitive Landscape
CCR5 Inhibitors – Competitive Landscape 14 There are a total of 28 unique assets that target CCR5 Monoclonal antibodies: Leronlimab (SC) HGS004 (IV – suspended) HGS1025 (IV – suspended) To date only Selzentry (maraviroc) has been approved (for HIV Tx) Source: BioMedTracker (July 2022), CytoDyn Analy
Slide 15: CCR5 Inhibitors – Indications Studied
CCR5 Inhibitors – Indications Studied 1 2 2 2 2 2 2 3 18 Undisclosed Renal Disease/Failure Primary Sclerosing cholangitis (PSC) PBC & Hepatic Fibrosis PanC Neuropathic Pain Neurology – Other Liver Failure / Cirrhosis Ischemic Stroke Hep C Drug Toxicity Diabetic Neph. DME DM Type II COPD BC GVHD Soli
Slide 16: CCR5 Inhibitors – Active Development Pipeline
CCR5 Inhibitors – Active Development Pipeline 16 Preclinical IND Phase 1 Phase 2 Phase 3 NDA/BLA Approved Selzentry GSK HIV/AIDS Tx Leronlimab CytoDyn NASH & Solid Tumors BMS-813160 BMS PanC / CRC Vicriviroc Merck CRC Cenicrivoc AbbVie HIV/AIDS Tx SB-728-T Sangamo HIV/AIDS Tx Cenicrivoc AbbVie PBC C
Slide 17: Unique Binding & Immunomodulating Properties
Unique Binding & Immunomodulating Properties CCR5 CCR5 352 aa 40.6 kDa O-linked glycosylation N-terminus Extracellular NH2 ECL1 ECL2 ECL3 Cytoplasmic phosphorylation palmitoylation 20 31 54 67 102 125 168 144 219 258 235 269 279 303 COOH 352 17
Slide 18: Leronlimab Clinical Development History
Leronlimab Clinical Development History 18 Leronlimab has been studied in over 1500 patients across 20+ clinical trials Infectious Disease HIV Treatment COVID-19 Treatment Oncology TNBC Basket Trial Liver Disease NASH Autoimmune GvHD
Slide 19: Leronlimab Clinical Development History
Leronlimab Clinical Development History 19 Leronlimab has been studied in over 1500 patients across 20+ clinical trials Clinical Hold Infectious Disease HIV Treatment COVID-19 Treatment Oncology TNBC Basket Trial Liver Disease NASH Autoimmune GvHD
Slide 20: Clinical Hold Status with FDA
Clinical Hold Status with FDA 20 5 items requested by the FDA: Investigator Brochure – Submitted in September Development Safety Update Report – Submitted in October Safety Management Plan – Submitted in November Aggregate Safety Analysis – In progress Benefit Risk Analysis – In progress FDA review
Slide 21: Future Development
Qoronyn Future Development 2
Slide 22: Refocusing Pipeline on High Value Opportunities
Refocusing Pipeline on High Value Opportunities 22 NASH Oncology HIV CCR5 Blockade with Leronlimab Studying immunologically colder tumors Developing longer-acting agents Opportunities in NASH and HIV-NASH populations
Slide 23: Future Development for Leronlimab
Going forward CytoDyn is focusing on NASH, oncology, and earlier line HIV indications CytoDyn has already generated promising clinical signals in NASH and oncology Within NASH, CytoDyn is pursuing the broader NASH population as well as a segment of NASH patients with HIV, where CytoDyn is in a uniqu
Slide 24: Epidemiology for Future Indications
Epidemiology for Future Indications NAFLD & NASH Epidemiology (Prevelant Cases in the 7MM) Projected Number of Patients Millions 120 100 80 60 40 20 0 CAGR ~0.4% CAGR ~0.9% CAGR ~0.8% CAGR ~1.4% 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037 2038 2039 2040 2041 2042
Slide 25: NAFLD & NASH – Disease Background
NAFLD & NASH – Disease Background 25 The diagnosis of non-alcoholic fatty liver disease (NAFLD) requires evidence of hepatic steatosis and the lack of secondary causes of liver fat accumulation such as substantial alcohol consumption, long-term use of a steatogenic medicine, or monogenic hereditary
Slide 26: NAFLD & NASH – Disease Progression
NAFLD & NASH – Disease Progression THE NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) SPECTRUM REVERSIBLE REVERSIBLE IRREVERSIBLE IRREVERSIBLE Healthy liver 15-30% NAFLD 12-40% NASH 15-25% Cirrhosis ~7% Hepato-cellular carcinoma 50% Liver transplant / Death RISK FACTORS INCLUDE: - OBESITY – DIABETES – AR
Slide 27: HIV-NASH – Disease Background
HIV-NASH – Disease Background 27 The burden of liver-related morbidity remains high among HIV-infected patients, despite advances in the treatment of HIV and viral hepatitis. The impact of non-alcoholic fatty liver disease (NAFLD) is significant with a prevalence of up to 50%. Both HIV infection its
Slide 28: Metastatic CRC – Background and Treatment
Metastatic CRC – Background and Treatment 28 CRC typically develops through the proliferation of mucosal epithelial cells of the gastrointestinal (GI) wall, eventually forming a polyp or adenoma. As with many other cancers of the GI tract, the vast majority (>95%) are adenocarcinomas. CRC stands as
Slide 29: Breast Cancer HR+/HER2- – Disease Background
Breast Cancer HR+/HER2- – Disease Background 29 Hormone receptor-positive (HR+) is the most common breast cancer subtype, with approximately 70% of breast cancers presenting with overexpression of estrogen receptors, progesterone receptors, or both. Overexpression of the hormone receptors allows est
Slide 30: NASH & Leronlimab
NASH & Leronlimab 30 Mazen Noureddin, M.D., M.H.Sc. Director of the Houston Liver Institute
Slide 31: Background - Non-Alcoholic Steatohepatitis (NASH)
Background - Non-Alcoholic Steatohepatitis (NASH) Non-alcoholic steatohepatitis (NASH) is a chronic liver disease characterized by the presence of hepatic inflammation and cell injury due to hepatic fat accumulation (steatosis) in ≥5% of hepatocytes Patients with advanced fibrosis due to NASH are at
Slide 32: NAFLD & NASH – Disease Progression
CytoDyn NAFLD & NASH – Disease Progression THE NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) SPECTRUM REVERSIBLE REVERSIBLE IRREVERSIBLE IRREVERSIBLE Healthy liver 15-30% NAFLD 12-40% NASH 15-25% Cirrhosis ~7% Hepato-cellular carcinoma RISK FACTORS INCLUDE: -OBESITY -DIABETES -ARTERIAL HYPERTENSION -DYS
Slide 33: NAFLD & NASH – Molecular Pathways to Fibrosis
NAFLD & NASH – Molecular Pathways to Fibrosis CCR2 and CCR5 as targets in NASH and liver fibrosis The accumulation of hepatic fat causes cellular stress and the release of chemokines, notably CCL2 (= MCP-1), from hepatocytes, Kupffer cells, endothelial and stellate cells. This promotes the infiltrat
Slide 34: The CCR5 Receptor as a therapeutic target in NASH
The CCR5 Receptor as a therapeutic target in NASH 34 CCR5 is G Protein coupled receptor. Acts as a receptor for chemokines. Cognate ligands include CCL3, CCL4, and CCL5 (Rantes) Macrophage-mediated inflammation and hepatic stellate cell activation are key drivers of progression at multiple stages of
Slide 35: CCR5 and the Inflammatory Response
CCR5 and the Inflammatory Response In NASH, liver homeostasis is impaired due to an accumulation of toxic lipids which can activate both Kupffer cells (KCs) and tissue-resident macrophages resulting in the production of fibrogenic cytokines and chemoattractant chemokines such as transforming growth
Slide 36: CDI-NASH-01: Design
CDI-NASH-01: Design Treatment Allocation (Leronlimab* vs. Placebo) Treatment given weekly (+-1 days relative to last dose Part1 Screening Double blind, Placebo-controlled (Randomized 1:1) Treatment Follow-up Week -4 Week 0 Week 1 Week 13 Week 14 Week 18** Treatment Allocation End of treatment visit
Slide 37: CDI-NASH-01: Results – Demographics
CDI-NASH-01: Results – Demographics Full analysis data set Number of participants Sex Male Female Number of participants Race Caucasian Black Number of participants Ethnicity Hispanic/ Latino Non-hispanic/ Latino Placebo (n=28) LRM 700 (n=22) LRM 350 (n=22) African American 37
Slide 38: CDI-NASH-01: Results – Adverse Events (Safety)
CDI-NASH-01: Results – Adverse Events (Safety) Vascular disorders Skin and subcutaneous tissue disorders Respiratory, thoracis and mediastinal disorders Renal and urinary disorders Nervous system disorders Metabolism and nutrition disorders Investigations Injury, poisoning and procedural complicatio
Slide 39: CDI-NASH-01 All Groups: Well Tolerated
CDI-NASH-01 All Groups: Well Tolerated Number of adverse events 0.0 1.0 2.0 3.0 Placebo 700mg 350mg 700mg HM P=0.882 P=0.674 39
Slide 40: CDI-NASH-01: Results – MRI PDFF
CDI-NASH-01: Results – MRI PDFF Proton density fat fraction (PDFF) – percent (percent change from baseline) Full analysis set (PDFF) -100 -50 0 50 100 150 p=0.136 p=0.006 p=0.014 p=0.008 p=0.020 p=0.027 9.85 3.75 -27.88 -1.09 -5.94 -4.37 -9.27 Placebo (n=28) 700mg (n=22) 700mg Haplotye (n=5) Pooled*
Slide 41: CDI-NASH-01: Results – Fibro-Inflammation by MRI cT1
CDI-NASH-01: Results – Fibro-Inflammation by MRI cT1 Iron corrected T1 mapping (CT1) – msec (absolute change from baseline) Full analysis set (CT1) -400 -200 0 200 400 p=0.059 p=0.013 p=0.013 p=0.021 p=0.011 p=0.009 -27.64 -2.73 -45.40 -13.30 -24.38 -42.0 -68 86 Placebo (n=28) 700mg (n=22) 700mg Hap
Slide 42: Improved Liver Function Tests
NASH01 350 mg Groups: Improved Liver Function Tests 42 Biomarker (mean change baseline to week 14) Placebo (n=28) 350 mg (n=22) 350 mg cT1 875 (n=14) 350 mg cT1 950 (n=8) Alkaline Phosphatase U/L -0.1 -2.82 -3.16 -7.25* ALT (Alanine Aminotransferase) U/L -0.11 -2.5 -2.7 -8.3 AST (Aspartate Amino
Slide 43: Reduced Chemotactic Proteins
NASH01 350 mg Groups: Reduced Chemotactic Proteins Biomarker (mean change baseline to week 14) Placebo (n=28) 350 mg (n=22) 350 mg cT1 875 (n=14) 350 mg cT1 950 (n=8) IL-1 (Interleukin 1) Beta pg/mL 0.16 0.00 0.00 0.00 IL-1RA (Interleukin 1 Receptor Antagonist) pg/mL 17.04 -28.36* -34.79** -26.25 IL
Slide 44: Reduced VCAM
CytoDyn NASH01 350 mg Groups: Reduced VCAM Biomarker (mean change baseline to week 14) Placebo (n=28) 350 mg (n=22) 350 mg cT1 875 (n=14) 350 mg cT1 950 (n=8) VCAM (Vascular Cell Adhesion Molecule) ng/mL 10.2 -93.8*** -94.2*** -81.0* S100A12 EN RAGE ng/mL 57.75 -80.09** -115.50** -169.0* EN RAGE (ex
Slide 45: Biomarker Changes: Inflammation Markers
Biomarker (mean change baseline to week 14) Placebo (n=28) 350 mg (n=22) 350 mg cT1 875 (n=14) 350 mg cT1 950 (n=8) IL-1 (Interleukin 1) Beta pg/mL 0.16 0.00 0.00 0.00 IL-1RA (Interleukin 1 Receptor Antagonist) pg/mL 17.04 -28.36* -34.79** -26.25 IL-6 (Interleukin 6) pg/mL 0.19 -0.28 -0.44 -0.30 IL-
Slide 46: Improvements in CV Markers
NASH01 350 mg Groups: Improvements in CV Markers Biomarker (mean change baseline to week 14) Placebo 350 350 cT1>850 350 cT1>950 Apolipoprotein A1S mg/dL -3.2 7.4 9.2 2.3 High Density Lipoprotein (HDL) U/L -1.1 2.05 2.0 0.4 LDL/HDL U/L 0.72 0.09 0.11 0.095 Neutrophil to Lymphocyte Ratio K/uL 0.038 -
Slide 47: CDI-NASH-01: Conclusions
CDI-NASH-01: Conclusions 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. PBO Part 2: Leronlimab 350 mg significantly reduced mean
Slide 48: Leronlimab in Oncology – Clinical Data
Leronlimab in Oncology – Clinical Data 4 8
Slide 49: Leronlimab in Patients with mTNBC - Clinical Data
Leronlimab in Patients with mTNBC - Clinical Data CD-07: TNBC Phase 1b/2 (n =10) NCT03838367 CD-07: TNBC Compassionate Use (n =16) NCT04313075 CD-09 Basket Study TNBC (n=2) NCT04504942 n = 28 mTNBC pts 49
Slide 50: mTNBC Patient Overview
mTNBC Patient Overview Data was available and pooled from three sources (n = 28 patients): All patients were listed as mTNBC n=16 were from Compassionate Use n=10 were from mTNBC trial n=2 were from Basket trial Patients received ≥1 dose of Leronlimab (range 1 - 33 doses) Doses ranged from 350mg - 7
Slide 51: Drugs Used in Combination with Leronlimab
Drugs Used in Combination with Leronlimab Carboplatin Pacitaxel + Carboplatin Gemcitabine + Carboplatin Eribulin Capecitabine Pemetrexed Atezolizumab nab-paclitaxel + Atezolizumab Abraxane + Atezolizumab Capecitabine + Atezolizumab No cross reactions were observed, but sample sizes are small 51
Slide 52: Safety Data: TRAEs, TEAEs, and SAEs
Safety Data: TRAEs, TEAEs, and SAEs (n=28) Treatment Emergent & Treatment Related Adverse Events TEAEs leronlimab grade 3-4 TEAEs leronlimab any grade TEAEs 3-4 TEAEs any grade only Leronlimab Related TNBC Compassionate+Basket n=1 n=7 n=8 n=68 0 10 20 30 40 50 60 70 80 Serious Adverse Events SAE rel
Slide 53: Safety Data: Top treatment related TEAEs
Safety Data: Top 13 treatment related TEAEs N=28 Percent of Patients =Grade 1/2 , =Grade 3/4 0% 5% 10% 15% 20% 25% 30% Fatigue Headache Constipation Nausea Cough Anemia Hyponatremia Neutrophil count Platelet count Hypertension Diarrhea gastrointestinal disorder hypothyroidism Only leronlimab related
Slide 54: KM Plots of Leronlimab Treated Population
KM Plots of Leronlimab Treated Population (n=28) *PFS for standard ≥3rd line therapy = 2.3 months **OS for standard ≥3rd line therapy = 6.5 months n=11/28 patients had bone and/or brain mets SG trial excludes brain or bone mets. Probability of PFS (%) Time (months) Greater than SOC Median PFS=3.8 mo
Slide 55: KM Plots of Population without Prior Brain Mets
KM Plots of Population without Prior Brain Mets 95% Confidence Interval Survival Curve PFS Total mTNBC Population ≥ 1 dose of Leronlimab (n = 22) *PFS for standard ≥3rd line therapy=2.3 months**OS for standard ≥3rd line therapy=6.6 months Probability of PFS (%) Time (months) Greater than SOC Median
Slide 56: KM Plots Based on Leronlimab Dose Used
KM Plots Based on Leronlimab Dose Used (n=28) Reference median for Standard of Care Reference median for SG Trial Probability of PFS (%) HR: 3.5 (95%CI=1.1-11.5, p=0.0835) Similar to SOC Time (months) n=19 350mg Dose 525-700mg Dose Time (months) 0% 25% 50% 75% 100% 0 3 6 9 12 Probability of OS (%) 3
Slide 57: KM Plots of Carboplatin & Leronlimab Population
KM Plots of Carboplatin & Leronlimab Population Patients includes mTNBC trial and Compassionate Use Trial PFS Total mTNBC Population ≥1 dose of Leronlimab (n = 13) Probability of PFS (%) Greater than SOC Median PFS = 3.9 months Time (months) 0% 25% 50% 75% 100% 0 3 6 9 12 OS Total mTNBC Population ≥
Slide 58: Changes in Tumor Growth by PET/CT
Changes in Tumor Growth by PET/CT Based on n=12 patients with RECIST Scans Change in Tumor Size after Induction (%) New Disease, Progressive Disease, or Death Dropped of Study Treatment Ongoing Time (months) Progressive Disease Stable Disease Partial Response 756-047A 707-002 708-005 708-004 703-005
Slide 59: Phase Ib/II mTNBC Changes in Tumors by PET/CT
Phase Ib/II mTNBC Changes in Tumors by PET/CT 350mg Leronlimab + Carboplatin 525mg Leronlimab + Carboplatin 700mg Leronlimab + Carboplatin Change in Target Lesion Size at Follow-Up Scan Percent Change in Target Lesion Size (%) * 701-001 and 707-005 progressed before follow-up scan Weeks 12 24 36 706
Slide 60: Changes in Circulating Tumor Associated Cells Predict Survival in mTNBC
Title: Changes in Circulating Tumor Associated Cells Predicts Progression Free and Overall Survival in Metastatic TNBC Patients after Induction with the Anti-CCR5 Drug Leronlimab Same TNBC patient population pooled from three leronlimab studies described previously CCR5 expression in a CAML (a) and
Slide 61: Leronlimab in Patients with CRC - Clinical Data
61 Leronlimab in Patients with CRC - Clinical Data CD-09 Basket Study CRC (n=6) NCT04504942 n = 6 CRC pts
Slide 62: Colorectal Patients with Available PET/CT
62 Colorectal Patients with Available PET/CT Progressive Disease -25% 25% 50% 0% -50% Change in Tumor Size after Induction (%) Partial Response Progressive Disease Stable Disease -75% -75% ** * 0 0% 100% Change in Tumor Size after Induction (%) 50% Time (months) 3 6 9 12 -100% -50% Partial Response
Slide 63: Microenvironment and IO in Cancer Therapy
Microenvironment and IO in Cancer Therapy 63 Stefan Glück MD PhD FRCPC Professor em. of Medicine Oncology Hematology Immunology Biotech
Slide 64: Paradigm shift in cancer therapy
64 Paradigm shift in cancer therapy Tumor cell Historical paradigm: Targeting tumor cells Lymphocyte NK New paradigm: Targeting immune cells W H Fridman et al., Nature Rev. Cancer, 12, 298-306, 2012
Slide 65: The Tumor Microenvironment (TME)
The Tumor Microenvironment (TME) DC Mast cell Macrophage MDSC Tumour core NK cell Immature DC Invasive margin Tumour bed FDC T cell CTL B cell Stroma TLS W H Fridman et al., Nature Rev. Cancer, 12, 298-306, 2012 65
Slide 66: Multiple Aspects of the Anti-Tumor Immune Response
Multiple Aspects of the Anti-Tumor Immune Response B cell B cell Antigen Tumor cell Fc Antibody Antibody medlated Phagocytosls T cell T cell Tumor Cell MHC-antigen Complex Death Tumor cell Macrophage Monocyte Marophage FC Antibody Tumor Cell FC Receptor Antigen Death Suppressor Cells TREG MDSC Immun
Slide 67: The Cancer Immune Cycle
67 The Cancer Immune Cycle Chemotherapy, vaccines Targeted therapies CD40 agonists TLR agonists OX40 Agonists Anti-CD47 Anti-CTLA-4 anti-CTLA-4 anti-PD-1/PD-L1 adoptive T cell therapy cyclophosphamide IDO-inhibirots anti-PD-1/PD-L1 3. Priming and activation 4. Trafficking of T cells to tumors 5. T c
Slide 68: The Nobel Prize in Physiology or Medicine 2018
The Nobel Prize in Physiology or Medicine 2018 Illustrations: Niklas Elmehed James P. Allison Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation” THE NOBEL ASSEMBLY AT KAROLINSKA INSTITUTET 68
Slide 69: Three Categories of Response to Anti-PD-1/PD-L1
Three Categories of Response to Anti-PD-1/PD-L1 Non-responders Moderate responders Higher responders PD1-PDL1 Monotherapy ORR Glioblastoma Prostrate Pancreatic CRC MSS Cervical Endometrial Mesothelioma Ovarian SCLC HCC Breast NSCLC H&N Renal Bladder Esophageal Gastric Melanoma ORR (%) 69
Slide 70: Indication Selection and Patient Segmentation
Indication Selection and Patient Segmentation Based on Categories of Tumor Immune Profile Phenotypic profile IFNg/Cytolytic Signature Other molecular signature Disease Immune Profile Mutational burden Antigen processing machinery and presentation Pre-Existing Immunity (20-40%)? Non-functional Immune
Slide 71: Chemotherapy: Pleiotropic Stimulatory Effects on the Immune System
Chemotherapy: Pleiotropic Stimulatory Effects on the Immune System T cell function & Th1 and MPh polarization Increase in antigen presentation/crosspresentation via dendritic cells; MHC I upregulation; epitope spreading Chemo therapy Proinflammatory cytokines IL-2 IL-15 IFN-y Treg&MDSC depletion tum
Slide 72: Unique MoA of Leronlimab in Immuno-Oncology
72 Unique MoA of Leronlimab in Immuno-Oncology 1 2 3 4 5 Macrophage Repolarization - conversion of M2 macrophages (pro-tumor) into M1 macrophages (anti-tumor) Reduction of metastatic tumor volume and reduced metastasis Prevents Tumor Angiogenesis - CCL5 (RANTES) promotes VEGF-dependent angiogenesis
Slide 73: The Potential Role of CCR5 in the TME
73 The Potential Role of CCR5 in the TME Ward ST, Li KK, Hepburn E, Weston CJ, Curbishley SM, Reynolds GM, Hejmadi RK, Bicknell R, Eksteen B, Ismail T, Rot A, Adams DH. The effects of CCR5 inhibition on regulatory T-cell recruitment to colorectal cancer. Br J Cancer. 2015 Jan 20;112(2):319-28. doi:
Slide 74: Leronlimab in Patients with mTNBC - Clinical Data
Leronlimab in Patients with mTNBC - Clinical Data 74 CD-09 Basket Study TNBC (n=2) NCT04504942 CD-07: TNBC Compassionate Use (n =16) NCT04313075 n = 28 mTNBC pts CD-07: TNBC Phase 1b/2 (n =10) NCT03838367
Slide 75: Results from CTC and CAML Studies in mTNBC
Results from CTC and CAML Studies in mTNBC Changes in Circulating Tumor Associated Cells Predicts Progression Free and Overall Survival in Metastatic TNBC Patients after Induction with the Anti-CCR5 Drug Leronlimab 75
Slide 76: Results from CD-07: TNBC Phase 1b/2
Results from CD-07: TNBC Phase 1b/2 A phase 1b/2 study of leronlimab combined with carboplatin in patients with CCR5+ metastatic Triple-Negative Breast Cancer (mTNBC) 76
Slide 77: Overall Conclusions for mTNBC Studies
77 Overall Conclusions for mTNBC Studies Based on the analysis of 28 mTNBC patients treated with leronlimab who had failed ≥1 line of previous therapy and its historical comparison with SOC chemotherapy treatment or Sacituzumab Govitecan (SG) treatment, including those with brain or bone metastases:
Slide 78: Hallmarks of Cancer — new additions
Sustaining proliferative signaling Evading growth suppressors Nonmutational epigenetic reprogramming Avoiding immune destruction Enabling replicative immortality Tumor-promoting inflammation polymorphic microbiomes Activating invasion & metastasis Inducing or accessing vasculature Senescent cells Ge
Slide 79: "The Promise"
“The Promise” Control Chemotherapy/Targeted therapies Immune checkpoint blockade Immunotherapy combinations Enriched population Survival Time Rlbas A. Presented at: BIT’s 3rd Annual World Congress of Microbes (WCM); 30 Julty – 1 August 2013: Wuhan, China, Rlbas A, et al. Clin Cancer Res. 2012;18(2):
Slide 80: CCR5 in HIV Prevention and Cure
CCR5 in HIV Prevention and Cure 80 Jonah B. Sacha, Ph.D. Oregon Health & Science University
Slide 81: CCR5 is Critical in Sexual Transmission of HIV
CCRS is Critical in Sexual Transmission of HIV CytoDyn LETTERS TO NATURE Resistance to HIV-1infection In caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene MichelSamson ·,Frederick Ubert , Benjamin J. Ooranzt, Joseph Ruckert, Corinne Uesnardt, Claire-Michele Farber§, S
Slide 82: CCR5 in HIV Cure
CCR5 in HIV Cure Patient No More Timothy Brown-a.k.a. “the Berlin Patient”-is the Man Who Once Had HIV. “Berlin patient” Timothy Brown HIV remission 13 years 82
Slide 83: CCR5 in HIV Cure
CCR5 in HIV Cure Patient No More Timothy Brown-a.k.a. “the Berlin Patient”-is the Man Who Once Had HIV. “Berlin patient” Timothy Brown HIV remission 13 years “London patient” Adam Castillejo HIV remission >4 years 83
Slide 84: CCR5 in HIV Cure
CCRS in HIV Cure cytoDyn Patient No More Timothy Brown-a.k.a. "the Bertin Patient" is the Man Who Once Had HIV. a International Maternal Pediatric Adolescent AIDS Clinical Trials Network 84 IMPAACT P1107 Team Presents First Known Case of Woman with HIV Remission
Slide 85: How to Mimic CCR5Δ32/Δ32 Phenotype?
85 How to Mimic CCR5Δ32/Δ32 Phenotype? CD4 T cell CD4 CCR5 CD4 T cell CD4 CCR5 Leronlimab Leronlimab
Slide 86: Leronlimab as PrEP for HIV
Leronlimab as PrEP for HIV nature communications Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission Xiao L. Chang, Gabriela M. Webb, … Jonah B. Sacha + Show authors Uninfected (%) Number of challenges Controls 10 mg/kg p = 0.001 50 mg/kg p = 0.0005 Leronlimab can pharmacol
Slide 87: Long-Acting Injectables for PrEP
Long-Acting Injectables for PrEP Science Logn-Acting Integrase Inhibitor Protects Macaques from Intrarectal Simian/Human Immunodeficiency Virus Chasity D. Andrews, 1 William R. Spreen, 2 Hiroshi Mohri,1 Lee Moss,2 Susan Ford,2 Agegnehu Gettie,1 Kasi Russell-Lodrigue,3 Rudolf P. Bohm,3 Cecilia Cheng-
Slide 88: Long-Acting Injectables for PrEP
Long-Acting Injectables for PrEP Science Logn-Acting Integrase Inhibitor Protects Macaques from Intrarectal Simian/Human Immunodeficiency Virus Chasity D. Andrews, 1 William R. Spreen, 2 Hiroshi Mohri,1 Lee Moss,2 Susan Ford,2 Agegnehu Gettie,1 Kasi Russell-Lodrigue,3 Rudolf P. Bohm,3 Cecilia Cheng-
Slide 89: Long-Acting Leronlimab for PrEP?
Long-Acting Leronlimab for PrEP? Plasma Leronlimab (ug/ml) Day post-leron 24957 32726 33897 34140 89
Slide 90: Long-Acting Leronlimab for PrEP?
Long-Acting Leronlimab for PrEP? Plasma Leronlimab (ug/ml) Day post-leron 24957 32726 33897 34140 Blood %CCR5 occupied (CCR5+ CD4+ T cells) Day post-leron Plasma anti-leronlimab IgG (reciprocal dilution) Day post-leron 90
Slide 91: CCR5 in HIV Cure
CCR5 in HIV Cure Patient No More Timothy Brown – a.k.a. “the Berlin Patient” – is the Man Who Once Had HIV. International Maternal Pediatric Adolescent AIDS Clinical Trials Network IMPAACT P1107 Team Presents First Known Case of a Woman with HIV Remission 91
Slide 92: CCR5 in HIV Cure: AAV Vectors
CCR5 in HIV Cure AAV Vectors Advance the Frontiers of Gene Therapy Technological developments and therapeutic applications of third-generation AAV vectors. 92
Slide 93: Long-Acting Leronlimab for Functional Cure?
Long-Acting Leronlimab for Functional Cure? Leronlimab (ug/ml) weeks post-AAV/Leronlimab LA %CCR5 occupied (CD4+CCR5+ T cells) weeks post-AAV/Leronlimab LA anti-Leronlimab IgG (plasma reciprocal dilution) weeks post-AAV9-Leronlimab %CCR5 occupied (CD4+CCR5+ T cells) weeks post-AAV/Leronlimab LA SHIV
Slide 94: Potential of Long-Acting Leronlimab for HIV
Potential of Long-Acting Leronlimab for HIV 1. Prevention of HIV infection 2. Functional cure (control of viremia) %CCR5 occupied (CD4+CCR5+ T cells) weeks post-AAV/Leronlimab LA SHIV pVL CCR5 RO pVL 94
Slide 95: Closing Remarks
Boronyn Closing Remarks 95
Slide 96: Refocusing Pipeline on High Value Opportunities
Refocusing Pipeline on High Value Opportunities 96 NASH Oncology HIV CCR5 Blockade with Leronlimab Studying immunologically colder tumors Developing longer-acting agents Opportunities in NASH and HIV-NASH populations
Slide 97: Refocusing Pipeline on High Value Opportunities
Refocusing Pipeline on High Value Opportunities 97 NASH Oncology HIV CCR5 Blockade with Leronlimab Studying immunologically colder tumors Developing longer-acting agents Opportunities in NASH and HIV-NASH populations Raise capital and execute trials Invest in the Future Seek co-development partners
Slide 98: Potential Timeline for Clinical Development
NASH will be the priority, other indications (NASH-HIV, CRC, and BC) are funding dependent 98 Potential Timeline for Clinical Development* Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 NASH trial start * Non-Binding timeline project
Slide 99: What We Expect in 2023
99 What We Expect in 2023 Lifting of the Partial Clinical Hold in HIV Financing to fund operations and achieve value inflection Initiating a NASH trial Invest in and advance a long-acting CCR5 molecule Continued contributions in medical meetings and peer-reviewed publications Continuing to reshape o
Slide 100: CytoDyn's Mission
CytoDyn’s Mission 100 A focused and disciplined clinical development strategy A value-generating path, resulting in economic returns for our investors A moral obligation to generate therapies to improve people’s lives