Mink Therapeutics, Inc. · NASDAQ:INKT
Mink Therapeutics — Investor Day (November 2022)
92 slides from Mink Therapeutics's investor day presentation, Nov 10, 2022
Slide 1: R&D Day November 10th, 2022
@,MINK _ R&D 4 DAY November 10th, 2022
Slide 2: Disclaimer and Forward-Looking Statements
Disclaimer and Forward-Looking Statements This presentation contains forward-looking statements that are based on management's beliefs and assumptions and on information currently available to management. All statements other than statements of historical facts contained in this presentation are for
Slide 3: MiNK Therapeutics advancing novel medicines and optimal combinations
MiNK Therapeutics advancing novel medicines and optimal combinations that are accessible and scalable Jennifer Buell, Ph.D. President & Chief Executive Officer MiNK Therapeutics
Slide 4: Invariant Natural Killer T Cells
4 Invariant Natural Killer T Cells iNKTs Wolf, B et al. Frontiers in Immunology. 2018; Gao et al, Oncologist 2021; Yamasaki et al, Clin Immunol 2011; Exley et al, Clin Cancer Res, 2017;
Slide 5: Draw Cells from Healthy Donors, Isolate & Expand, Administer
Draw Cells from Isolate & Administer Healthy Donors Expand Cells via Infusion
Slide 6: Dr. Manuel Hidalgo
Dr. Manuel Hidalgo Chief of the Division of Hematology and Medical Oncology at Weill Cornell Medicine and New York- Presbyterian/Weill Cornell Medical Center
Slide 7: Cancer Treatment: What is Working and How Can We Improve?
Cancer Treatment: What is Working and How Can We Improve?
Slide 8: COI Disclosure
COI Disclosure • BOD: BMS • Founder: Champions Oncology, Nelum Pharmaceuticals • Stock holder: Champions Oncology, Nelum Pharmaceuticals, Highlight Therapeutics, Oncomatrix, Inxmed, BMS, Agenus • Research support: PanCan, TBA alliance, Agenus, RANK Therapeutics • Honorarium: MiNK, Oncomatrix, Inxmed
Slide 9: Estimated Projection Cancer Incidence and Death
Estimated Projection Cancer Incidence and Death Rahib et al, JAMA Net 2021 9
Slide 10: Pillars of Cancer Care
Pillars of Cancer Care MORE OPTIONS FOR CANCER CARE CANCER CARE AdVaSHLONNWHI z > 4 fo} = = m rs] > a] = AdV4SHLOW3H) TVNOILIGVYL AdVasHL NOISIDSUd ancient times-present 1890s-present 1940s-present 1998-present 1997-present @® Weill Cornell Medicine 10 = NewYork-Presbyterian
Slide 11: Putative Targets and Inhibitors
Putative Targets and Inhibitors Collisson et al, Nat Can Rev 2019 11
Slide 12: Approved IO Targets
Approved IO Targets Ganesh et al, Nat Rev Gastroenterol Hepatol 2019 12
Slide 13: Pembrolizumab in MSI CRC
Pembrolizumab in MSI CRC Andre et al, NEJM 2020 13
Slide 14: Current IO in PDAC
Current IO in PDAC Renouf at al, Nat Com 2022 14
Slide 15: The Continuum of Immune Cell Therapies
The Continuum of Immune Cell Therapies Weber at al, Cell 2020 15
Slide 16: Ide-cel in RR Multiple Myeloma
Ide-cel in RR Multiple Myeloma Munshi et al, NEJM 2021 16
Slide 17: Challenges with CAR T cells
Challenges with CAR T cells 17
Slide 18: iNKT cells MOA
iINKT cells MOA Reduction of TME immuno-suppression Tumor Cells Weill Cornell Medicine Block! Kill cDid iTCR Se a NKG2DL > NKG2D TARGET, CAR got. DNAM1L c DNAM1 Direct Cytotoxicity T Cell Recruit/Activate / Anti-Tumor NK cell Cytokine Production 18 | iNKT Cells = NewYork-Presbyterian
Slide 19: Today we will hear…
Today we will hear… • Allogeneic unmodified iNKTs (agenT-797) show reductions in target and non-target lesions or disease stabilization in patients with solid tumor cancers when administered alone [27%] and in combination with pembrolizumab (KEYTRUDA®) or nivolumab (OPDIVO®) [66%]. • agenT-797 shows
Slide 20: Dr. Mark Exley, PhD
Dr. Mark Exley, PhD Scientific Advisory Board Member, MiNK • Expert in INKT biology and therapeutics in cancers, infections, auto-immunity and inflammation. • Associate Editor of Clinical Immunology and >120 peer-reviewed publicatoins • Faculty at Harvard Medical School • Co-founder of NKT Therapeut
Slide 21: iNKT Cells are Distinct in the Cell Therapy Landscape
iNKT Cells are Distinct in the Cell Therapy Landscape, Combining both Innate and Adaptive Immunity Innate Adaptive Rapid Response Distinct T cells that possess the effector function of adaptive immune cells, but also the rapid activation kinetics of innate immune cells Dendritic Cell T Cell CD4+T Ce
Slide 22: iNKT Cells Directly Attack Tumor Cells, Recruit Host Immunity
iNKT Cells Directly Attack Tumor Cells, Recruit Host Immunity, and Reshape Tumor Microenvironment Reduction of M DSC iNKT Anti-Cancer Mechanism TME immuno- s uppres s ion Direct tumor killing Block /Kill Granzyme B secretion upon 2 iNKT-tumor interactions: iTCR – CD1d Invariant TCR binding to glycol
Slide 23: iNKTs Promote Superior Tumor Control and Survival Relative to T and NK Cells
iNKTs Promote Superior Tumor Control and Survival Relative to T and NK Cells CAR-iNKT Promote Superior Survival vs CAR-Ts iNKT Outperform NK Cells Through Through Direct Killing & Host Immunity Induction Intrinsic NK Function B-cell lymphoma model A375-FG melanoma xenograft NSG model • CD19-CAR-iNKT
Slide 24: iNKTs in ARDS and Viral Infections
iNKTs in ARDS and Viral Infections iNKT Anti-Infection Mechanism Direct viral killing DC – Recognition of CD1d ligands in diseased tissue and Maturation activation through the invariant TCR – Recognition of stress-signals through activating NK Recruit & Activate receptors, NKG2D, DNAM1 IFNγ Control
Slide 25: iNKT Cells Have Benefits Beyond Other Cell Therapies
iNKT Cells Have Benefits Beyond Other Cell Therapies iNKT Cells T Cells NK Cells T Cells Tumor homing and persistence POTENT CANCER KILLING Orchestrate innate and adaptive immune responses Modulate suppressive myeloid compartment No TCR engineering needed for allogeneic application ENHANCED TOLER
Slide 26: Dr. David Einstein, MD
Dr. David Einstein, MD Lead Investigator • Genitourinary Medical Oncologist, Beth Israel Deaconess Medical Center • Assistant Professor, Harvard Medical School • Director, GU Oncology Clinical Research, Beth Israel-Lahey Network • Principal Investigator of the DF/HCC GU Rapid Autopsy Program • Young
Slide 27: Allo-iNKTs Alone or With PD-1 Inhibitors Builds on Observations of Activity
Allo-INKTs (agent-797) Alone or In Combination with PD-1 Inhibitors Builds on Observations of Activity of iNKTs in Solid Tumors Autologous INKTs in Solid Tumors Clinical Outcomes Head and Neck Cancer ORR: 50% (SCCHN) Non-Small Cell SD: 67% (4/6) Lung Cancer (NSCLC) Advanced Hepatocellular mOS: 13 mo
Slide 28: iNKT Cells Plus Checkpoint Inhibitors Show Solid Tumor Elimination
iNKT Cells Plus Checkpoint Inhibitors Show Solid Tumor Elimination Syngeneic Checkpoint Inhibitor-Resistant Melanoma Tumor Model (B16-Ova) 300 Number of Metastases • Endogenous iNKTs activated by 200 administration of α-GalCer • Activated iNKTs show effective 100 tumor infiltration and reduction • C
Slide 29: Phase 1 Trial of agenT-797 Monotherapy or With Pembrolizumab or Nivolumab
Phase 1 Trial of agent-797 (allo-iNKTs) Monotherapy or in Combination with Pembrolizumab or Nivolumab in Solid Tumors Part 2 – agent-797 +/- pembro or nivo DL1: 300x10^6 cells Primary endpoints DL2: 1000x10^6 cells • Dose relationship and AEs 20-30 PD SOC pembro/nivo patients • Safety, PD, PK, DLTs
Slide 30: Phase 1 Trial of agenT-797: Overview
Phase 1 Trial of agent-797 (allo-iNKTs) Monotherapy or in Combination with Pembrolizumab or Nivolumab in Solid Tumors Phase 1 Overview DL1 DL1 DL2 4.3x106 cells/kg 4.3 x 106 cells/kg 1.4 x 107 cells/kg Total + pembro/nivo • Trial Launch May 2022 N=8 N=3 N=14 N=25 • Efficacy Evaluable/Enrolled: Age 1
Slide 31: agenT-797 Shows Early Signs of Clinical Activity in Solid Tumors
agenT-797 Shows Early Signs of Clinical Activity in Solid Tumors Reduction in Target and Non-TargetDL1, Lesions in Heavily MonoTx Preliminary Activity in Heavily Pre-treated Patients Pre-treated Patients DL1, ComboTx DL2, MonoTx DL1, MonoTx • Reduction of target and non-target lesions or disease DL1
Slide 32: agenT-797 Can Be Dosed Alone and In Combo with Favorable Tolerability
agenT-797 Can Be Dosed Alone and In Combo with Anti-PD-1 with Favorable Tolerability Profile No DLTs and Few Related AEs No Cytokine Release Syndrome or agenT-797 Shows Modulation of Neurotoxicity IFNƔ Solid Summary of Related Adverse Events Tumors (n=25) Any AE grade ≥ 3 8 (32%) 140 DL1, MonoTx Any
Slide 33: Phase 1 Trial of agenT-797 in R/R Multiple Myeloma
Phase 1 Trial of agenT-797 in R/R Multiple Myeloma After ≥3 Prior Lines of Therapy Dose level 3 Primary endpoints AGENT-797 (1000x10^6 cells) • Dose relationship and AEs 3-6 patients • Safety, PD, PK, DLTs and MTD Dose level 2 Secondary endpoints AGENT-797 • Persistence of AGENT-797 (300 x 10^6 cell
Slide 34: agenT-797 Shows Early Clinical and Biomarker Activity in r/r Multiple Myeloma
agenT-797 Shows Early Clinical and Biomarker Activity in r/r Multiple Myeloma After ≥3 Prior Lines of Therapy Durable disease stabilization for over 10 months Case Study: Reduction in M-spike protein and in heavily pre-treated patients stabilization of plasma cell levels Patient Dose Level # Prior L
Slide 35: agenT-797 Administered Without Lymphodepletion in MM with Favorable Safety
agenT-797 Administered Without Lymphodepletion in MM with a Favorable Safety Profile No DLTs and Few Related AEs No Cytokine Release Syndrome or Neurotoxicity Multiple Myeloma (n=12) Any AE grade ≥ 3 2 (16.7%) Any TRAE grade ≥ 3 0 (0%) Any irAE NR Any TRAE leading to discontinuation 0 (0%) Any TRAE
Slide 36: Summary and Future Directions
Summary and Future Directions • agenT-797 alone and in combination with anti-PD-1 is well tolerated across multiple doses and shows early signals of clinical and biomarker activity in patients with solid tumors and multiple myeloma • No evidence of cytokine release, neurotoxicity, or immune related
Slide 37: Sapana Pokharel, PhD
Abstract Number: 372 agenT-797, a native allogeneic “off-the- shelf” invariant natural killer T (iNKT) cell therapy product improves effector Sapana Pokharel, PhD functions within the tumor Therapeutics Scientist microenvironment MiNK Therapeutics
Slide 38: Novel therapeutic approaches are required for redirecting dysfunctional T cells and myeloid cells
Novel therapeutic approaches therapies are required for redirecting dysfunctional T cells and myeloid cells for anti-tumor functions • T cell exhaustion is a common phenomenon that occurs due to prolonged antigen exposure during cancer and chronic viral infection. Despite the promising therapeutic e
Slide 39: agenT-797 Improved Anti-Tumor Activity of Immune Cells in the Tumor Microenvironment
agenT-797 Improved Anti-Tumor Activity of Immune Cells that are Present in the Tumor Microenvironment Enhanced Cytotoxic Response Promote trans-activation of Preferential killing of immuno- of partially Exhausted T cells Dendritic cells suppressive M2 macrophages Soluble factor Partially agenT-797 f
Slide 40: Optimizing iNKT Cells
Optimizing iNKT Cells Our Platforms for CAR-INKT and INKT-Engagers Marc van Dijk Chief Scientific Officer MiNK Therapeutics
Slide 41: iNKT Cell Anti-Tumor Activity Can be Enhanced by CARs and Engagers
iNKT Cell Anti-Tumor Activity Can be Enhanced by CARs and Engagers Bispecific iNKT CARs cell engagers iNKT Tumor Cell Cell CARDISTM Platform Bispecific iNKT Cell Engager Platform CARs to surface-expressed antigens IgG-based iNKT cell engagers 41
Slide 42: iNKT Cell Anti-Tumor Activity Can be Enhanced by CARs and Engagers
iNKT Cell Anti-Tumor Activity Can be Enhanced by CARs and Engagers iNKT Anti-Cancer Mechanism Direct tumor killing Granzyme B secretion upon 2 iNKT-tumor interactions: – Invariant TCR binding to glycolipids presented by CD1d – NKG2D and DNAM-1 detection of tumor cell ligands Recruitment of host immu
Slide 43: CARDIS Platform - Chimeric Antigen Receptors for iNKT cells
CARDIS Platform - Chimeric Antigen Receptors for iNKT cells Functional components Tumor Recognition Intracellular Signaling CARDISTM Platform CARs to surface-expressed antigens 43
Slide 44: CARDIS Platform Enables Rapid Selection of Potent and Highly Specific CARs
CARDIS Platform Enables Rapid Selection of Potent and Highly specific CARs Fully Human phage libraries Phage Libraries • Highly diverse libraries • No sequence liabilities ScFv Phage Screening scFv Binders • Binding to antigen / cells CAR Display Mammalian Display library • NFAT-GFP reporter • Direc
Slide 45: CAR Display – the value-add step of CARDIS
CAR Display – the value-add step of CARDISTM Synthetic phage libraries Phage Libraries • Highly diverse libraries (>1010) • No sequence liabilities ScFv Phage Screening scFv Binders • Binding to antigen / cells • 2-3 weeks CAR Display Mammalian Display library • NFAT-GFP reporter • Direct Functional
Slide 46: CAR Display – the value-add step of CARDIS
CAR Display – the value-add step of CARDISTM Synthetic phage libraries Phage Libraries • Highly diverse libraries (>109) • No sequence liabilities ScFv Phage Screening scFv Binders • Binding to antigen / cells • 2-3 weeks • 6x106 binders CAR library Mammalian Display • NFAT-GFP reporter • Direct Fun
Slide 47: MiNK CAR-iNKT portfolio – our most advanced programs
MiNK CAR-iNKT portfolio – our most advanced programs CD1d iTCR Tumor Cells NKG2DL NKG2D secreted IL15 DNAM1L DNAM1 IL15 TARGET CAR • MiNK- 215: FAP-CAR-iNKT-IL-15 • MiNK- 413: BCMA-CAR-iNKT IL-15 Adapted from: Wolf, B et al. Frontiers in Immunology. 2018
Slide 48: Xavier Michelet, PhD
Abstract Number: 358 Development of an allogenic FAP-CAR- iNKT product to target tumor stroma and Xavier Michelet, PhD modulate the Tumor Microenvironment Associate Director of Preclinical Immunobiology, MiNK Therapeutics
Slide 49: MiNK FAP-CAR-IL-15 iNKT Cell Therapy Promotes Curative Responses in NSCLC Mice
MiNK FAP-CAR-IL-15 iNKT Cell Therapy Promotes Curative Responses in NSCLC Tumor-Bearing Mice • MiNK FAP-CAR iNKT delays tumor engraftment through changing the tumor microenvironment and preventing tumor growth • FAP-CAR-IL-15 iNKT appears to eliminate tumors more effectively than tumor specific T ce
Slide 50: MiNK FAP-CAR-IL-15 iNKT Cell Therapy Promotes Curative Responses in NSCLC Mice
MiNK FAP-CAR-IL-15 iNKT Cell Therapy Promotes Curative Responses in NSCLC Tumor-Bearing Mice • NSCLC xenograft tumor model developing an immunosuppressive stroma resistant to tumor-specific T cell infiltration and activity • FAP-CAR-IL-15 iNKT delays tumor engraftment in targeting the stroma that su
Slide 51: FAP-CAR-IL-15 iNKT Enhances Infiltration of Tumor-Specific CD8+ T cells
FAP-CAR-IL-15 iNKT Enhances Infiltration of Tumor-Specific CD8+ T cells to Clear Tumor FAP-CAR-IL-15 iNKT T cells only T cells only FAP-CAR-IL-15 + T cells iNKT + T cells Tumor cells Tumor specific 800 CD8+ T cells 600 Nucleus Cells (#) 400 200 0 0 5 10 15 20 25 30 Distance CD8+ T cells to Tumor cel
Slide 52: Eleni Chantzoura, PhD
Abstract Number: 322 MiNK-413: a Next generation armored allogenic BCMA-CAR-iNKT product Eleni Chantzoura, PhD Director Discovery, MiNK
Slide 53: MiNK-413: Not another BCMA CAR T-Cell Therapy
MiNK-413: Not another BCMA CAR T-Cell Therapy
Slide 54: Therapy in Multiple Myeloma: Room for Improvement
Therapy in Multiple Myeloma: Room for Improvement ❑ Sub-optimal CARs ❑ Clinical Challenges ❑ Manufacturing Limitations 54
Slide 55: Sub-optimal CARs - Immunogenicity
Sub-optimal CARs - Immunogenicity 100 non-binders 80 non-activators binders % of clones Phage panning Phage output CAR T-cell 60 non-activators human BCMA CAR DNA library library binders 40 tonic signaling binders 20 specific activators 0 CARDIS: High-Throughput Identification of Functional CARs
Slide 56: Clinical challenges – Multiple Myeloma is still incurable
Clinical challenges – Multiple Myeloma is still incurable BCMA CAR iNKT cells do more than just kill the tumor cells
Slide 57: Manufacturing and Logistical Challenges
Manufacturing and Logistical Challenges Up to 5000 doses from a single healthy donor
Slide 58: MiNK-413: Not another BCMA CAR T-Cell Therapy
MiNK-413: Not another BCMA CAR T-Cell Therapy CARDIS: High-Throughput BCMA CAR iNKT cells do more Up to 5000 doses Identification of Functional CARs than just kill the tumor cells from a Single Healthy Donor Phage panning Phage output CAR T-cell human BCMA CAR DNA library library 100 non-binders 80
Slide 59: Unlocking the constraints of cell therapy manufacturing
Unlocking the constraints of cell therapy manufacturing to enable scalable, accessible, and affordable treatments Joy Zhou, PhD Head of CMC, MiNK Therapeutics
Slide 60: Curative Efficacy of Cell Therapy with Rapid Accessibility and Affordability
Curative Efficacy of Cell Therapy with Rapid Accessibility and Affordability MiNK unlocks constraints of cell therapy large scale manufacturing to enable an accessible and affordable treatment Available Autologous Cell MiNK Allogeneic Cell Products Therapy Dynamics Target cost of Goods (per treatmen
Slide 61: Internal Manufacturing Path to Achieve ≥700,000 Doses Per Year
Internal Manufacturing Path to Achieve ≥700,000 DOSES PER YEAR We’ve designed production capacity with commercial ready mfg suite to produce ≥ 700,000 doses/year production potential Cell expansion Harvest & Purification Formulating & Fill/Finish (2-3 weeks) (<1 day) (< 1 day) Proprietary reagents f
Slide 62: Dr. Terese Hammond
Dr. Terese Hammond • Program Medical Director, Providence Saint John’s Health Center and pulmonary critical care expert • Pioneering work in clinical and translational science in critical care of COVID-19
Slide 63: The Future of Cell Therapy and precision medicine for ARDS and critical illness
The Future of Cell Therapy and precision medicine for ARDS and critical illness
Slide 64: Mortality of Critical Illness Exceeds Most Cancers
Mortality of Critical Illness Exceeds Most Cancers • Mortality Rates • Sepsis: 25-50% • ARDS: 35-45% • COVID-19: 30.9% overall and 35.7% mechanically ventilated • COVID-19 ECMO: 40-70% • Ruptured AAA: 80% • SAH: 20-50% https://ourworldindata.org/cancer-death-rates-are-falling-five-year-survival-rate
Slide 65: iNKT Development in ARDS and Viral Infections
iNKT Development in ARDS and Viral Infections Versatile & critical cells for suppressing inflammatory cytokines, fighting infection, and reducing relapse in patients Acute Respiratory Distress (ARDS) Acute respiratory distress syndrome (ARDS) DC is inflammation driven respiratory failure in Maturati
Slide 66: VV-ECMO is Lung Bypass
VV-ECMO is LUNG BYPASS Gajkowski, Evan F., et al. "ELSO guidelines for adult and pediatric extracorporeal membrane oxygenation circuits." ASAIO Journal 68.2 (2022): 133-152.
Slide 67: agenT-797 in Moderate to Severe ARDS Secondary to COVID-19
agenT-797 (allogeneic unmodified iNKTS) in subjects with moderate to severe acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 (COVID-19) • All participants to receive a single infusion of agenT-797 in doses of 100, 300, 1000, × 10^6 cells • Subjects were eligible if they were infect
Slide 68: agenT-797 Shows Improved Survival and Favorable Safety Profile in Severe ARDS
agenT-797 Shows Improved Survival and Favorable Safety Profile in Severe ARDS 70% Survival Compared to Reduced Incidence of Secondary Increased Anti-Inflammatory 10% Case Control Infections, including Pneumonia Response N (%) Dose Dose Dose Level Level Level 3 1 2 (n=13) (n=3) (n=4) Pneumonia 2 (67)
Slide 69: agenT-797 is Well Tolerated With Potential for Redosing
agenT-797 is Well Tolerated With Potential for Redosing Transient Antibody Response No DLTs and Few Related AEs No Cytokine Release Syndrome Suggests Redosing Potential N (%) All doses (n=20) Any AE grade ≥ 3 19 (95) Any TRAE grade ≥ 3 1 (5) Any TRAE leading to 0 (0) discontinuation Any TRAE leading
Slide 70: iNKT Therapy Shifting the Paradigm for Critical Infections
INKT Therapy Shifting the Paradigm for Critical Infections • Severe lung infections induce hyper-inflammation causing life-threatening disorders • iNKT cells improve the disease course in severe viral infections of the lung • Destroy immunosuppressive MDSCs • Improve anti-viral immune responses • Re
Slide 71: Marco Purbhoo
agenT-797 Biosignatures in Solid Tumors and COVID-19/ARDS Marco Purbhoo Director Translational Research MiNK Therapeutics
Slide 72: agenT-797 Biosignatures in Solid Tumors and COVID-19/ARDS
agenT-797 Biosignatures in Solid Tumors and COVID-19/ARDS • agenT-797 represents a balanced iNKT cell-based drug product capable of responses across the pro- and anti- inflammatory spectrum • In solid tumors an anti-inflammatory tumor microenvironment suppresses immune cell infiltration and activati
Slide 73: agenT-797 Biosignatures in Solid Tumors and COVID-19/ARDS
agenT-797 Biosignatures in Solid Tumors and COVID-19/ARDS agenT-797 shows Pro-inflammatory signature in agenT-797 shows anti-inflammatory signature in patients with Solid Tumors patients with ARDS 140 6000 120 5000 100 4000 80 pg/ml pg/ml 3000 60 2000 40 20 1000 0 0 e R R R R 15 22 29 R 2 8 re R R R
Slide 74: Lydia Lynch, PhD
Lydia Lynch, PhD Scientific Advisory Board Member, MiNK • Director of the Metabolic Core and Principal Investigator of Lynch Lab Harvard Medical School. • Associate Professor of Medicine, Brigham and Women's Hospital, Harvard Medical School.
Slide 75: The Key Drivers and Regulators of Immunity – a Perspective
The Key Drivers and Regulators of Immunity – a Perspective Innate T cells are an unappreciated, and understudied regulator in the body CD4 CD8 iNKT T MAIT T cell T cell cell cell cell DIVERSE TCR INVARIANT TCR LESS DIVERSE TCR INVARIANT TCR pAg ? lipids Metabolite peptides ? ? MHC II MHC I CD1d B
Slide 76: Some reasons for limited success of ACT for solid tumors
Some reasons for limited success of ACT for solid tumors
Slide 77: Features that make innate T cells a preferred choice for adoptive cell therapy
Features that make innate T cells a preferred choice for adoptive cell therapy
Slide 78: Which innate T cell is best? Unbiased competition
Which innate T cell is best? Unbiased competition Can kill in vivo Can kill Can kill Help other cells kill Can produce IL-17 in tumors No IL-17 in human tumor Known antigen – can expand May require antigen Dont require antigen Limited expansion Limited expansion
Slide 79: iNKT cells naturally address problems with current ACT
iNKT cells naturally address problems with current ACT
Slide 80: iNKT cells naturally address problems with current ACT
iNKT cells naturally address problems with current ACT MiNK Therapeutics have demonstrated how iNKT cells are an excellent choice for immunotherapy. They have proven that their inherent features that we long suspected would be beneficial for ACT, actually are
Slide 81: How might we make them even better?
How might we make them even better? MiNK FAP-CAR-IL-15 iNKT Cell BCMA CAR iNKT-Cell CARDISTM Platform Future Approach: Metabolic Reprogramming
Slide 82: Mitochondrial fitness essential for tumor activity
Mitochondrial fitness essential for tumor activity Jenkins et al. 2021, Antibodies
Slide 83: Transcriptional and metabolic programs associated with iNKT subsets and states
Transcriptional and metabolic programs associated with iNKT subsets and states scRNA Seq - 16,500 iNKT cells
Slide 84: Improved metabolic fitness
Improved metabolic fitness Antimycin Oligomycin FCCP Rotenone Gen 1 100 Gen 2 OCR (pmoles/min) 50 TMRM 0 0 15 30 60 90 Time (minutes) MTG Oligomycin 2-DG Mitotracker TMRM 100 ✱✱ ✱✱ 15000 20000 ECAR (mpH/min) 10000 5000 50 4000 MFI 4000 MFI 2000 2000 0 0 15 35 90 0 0 Gen 1 Gen 2 Gen 1 Gen 2 Time (min
Slide 85: Gold standard test for mitochondrial fitness and stability of phenotype is in vivo
Gold standard test for both mitochondrial fitness and stability of phenotype is in vivo Gen 1 Gen 2
Slide 86: Gen 2 cells persist in tumor
Gen 2 cells persist in tumor Gen 1 Gen 2 Gen 2 Day 56 10 5 ✱ ✱ 2500 absolute cell count Tumor volume (mm3) 2000 1500 10 4 1000 500 0 MTG TMRM 10 3 S 1 2 PB en en G G 1 2 1500 2000 ✱ ✱ en en G G 1500 1000 Tumor 10,000 vs 120,000 MFI MFI 1000 500 Bone Marrow: 10,000 vs 900,000 500 0 0 Gen 1 Gen 2 Gen
Slide 87: iNKT cells are the Swiss Army Knife of the immune system
iNKT cells are the Swiss Army Knife of the immune system Cancer Graft Versus Infection Host Disease Requirement for checkpoint Metabolism efficacy - Type 2 Diabetes - Reduction of inflammation Weight and Energy associated with obesity Expenditure
Slide 88: Harness transcriptional and metabolic programs associated with iNKT subsets
Harness transcriptional and metabolic programs associated with iNKT subsets for different conditions -Anti-tumor action -Infection -Anti-inflammatory -Metabolic disorder - GVHD
Slide 89: iNKT cells patrolling adipose
iNKT cells patrolling adipose iNKT cells
Slide 90: Anti-inflammatory iNKT cells reverse metabolic disease in obesity
Anti-inflammatory iNKT cells reverse metabolic disease in obesity Adipose Weight Glucose Tolerance Test 2 3 * 1 weight change (g) Weight (g) 2 ** 0 -1 1 -2 0 -3 SFD WT -4 WT HFD + Vehicle VEH aGC Ja18KO HFD + aGalCer WT HFD + aGalCer Lynch et al Nature Immunology 2015 Lynch et al Immunity 2012
Slide 91: Innate iNKT cells
Innate iNKT cells • Versatile • Transactivate of other cells – Conductor of the immune orchestra • Can be expanded • Can be manipulated for distinct functions
Slide 92: R&D Day November 10th, 2022
@,MINK _ R&D 4 DAY November 10th, 2022