Slide 1: Unlocking the power of the immune system to fight cancer and autoimmune disease
Unlocking the power of the immune system to fight cancer and autoimmune disease I Immutep Corporate Presentation – September 2024 (ASX: IMM; NASDAQ: IMMP)
Slide 2: Forward-Looking Statements
Forward-Looking Statements The purpose of the presentation is to provide an update of the business of Immutep Limited ACN 009 237 889 (ASX:IMM; NASDAQ:IMMP). These slides have been prepared as a presentation aid only and the information they contain may require further explanation and/or clarificati
Slide 3: Deep LAG-3 Pipeline in Oncology & Autoimmune Diseases
Deep LAG-3 Pipeline in Oncology & Autoimmune Diseases Program Indication Preclinical Phase I Phase II Late Stage# Collaborations Commercial Rights 1L Non-Small Cell Lung Cancer (NSCLC) TACTI-004 | Efti + Pembrolizumab + Chemo a 1L Head & Neck Squamous Cell Carcinoma (HNSCC) TACTI-003 | Efti + Pembro
Slide 4: Company Overview
Company Overview Pure-play LAG-3 company with deep pipeline in oncology & autoimmune diseases: • Multiple LAG-3 Programs – Four clinical-stage assets and one preclinical program • Upcoming Milestones – Multiple data updates from clinical programs Lead candidate Efti addressing therapeutic gaps acros
Slide 5: LAG-3 Newest Entrant to Immuno-Oncology (IO) Landscape
LAG-3 Newest Entrant to Immuno-Oncology (IO) Landscape Immune Checkpoint Discovery and Clinical Studies* Regulatory Approval Timeline of Immuno-Oncology (IO) Therapies** OPDIVO & KEYTRUDA OPDIVO & YERVOY & Chemo Relatlimab (anti-LAG-3) Number of studies YERVOY OPDIVO (anti-CTLA-4) (anti-PD-1) KEYTRU
Slide 6: Pioneering LAG-3 Immunotherapy Portfolio
Pioneering LAG-3 Immunotherapy Portfolio LAG-3 Immutep has designed multiple first-in-class Antigen-presenting cells (APC) T Cell therapeutics targeting either MHC Class II molecules on antigen-presenting cells (APC) or LAG-3 on T-cells MHC Class II to fight cancer & autoimmune disease Targeting MHC
Slide 7: Efti
Efti A proprietary soluble LAG-3 protein and first-in-class MHC Class II agonist
Slide 8: Efti: A Soluble LAG-3 'Key' to Stimulate Immune System via MHC II
Efti: A Soluble LAG-3 ‘Key’ to Stimulate Immune System via MHC II Eftilagimod alfa (efti) A first-in-class soluble LAG-3 fusion protein Soluble Human IgG1 with high affinity for a subset of MHC Class II LAG-3 backbone molecules on antigen-presenting cells (APCs) Activated CD4+ Efti Mature Monocytes
Slide 9: Systemic Immune Effect Leading to Positive Clinical Outcomes
Systemic Immune Effect Leading to Positive Clinical Outcomes Encouraging data from efti in combination with IO, chemotherapy, radiotherapy across multiple indications Non-Small Cell Lung Cancer Efti’s subcutaneous Head & Neck Squamous Cell Carcinoma delivery drives systemic anti-cancer immune respon
Slide 10: Differentiated Approach in Oncology
Differentiated Approach in Oncology Efti has complementary action with immune checkpoint inhibitors (ICIs) like anti-PD-(L)1 therapy Activated Dendritic Cell Innate Adaptive Anti-PD-1 Immunity Immunity antibody NK CXCL10 CD8+ Cell T Cell PD-1 APC Efti T Cell CD4+ Monocyte IFN-ƴ T Cell Efti’s unique
Slide 11: Substantial Commercial Opportunity in Combination with ICIs
Substantial Commercial Opportunity in Combination with ICIs Encouraging Clinical Data from Efti in Combination with KEYTRUDA® became the world’s top selling Anti-PD-(L)1 Therapy including KEYTRUDA® & BAVENCIO® drug in 2023 with sales exceeding $25 billion • More than double Overall Survival of KEYTR
Slide 12: Clinical Trials Target Large Addressable Markets
Clinical Trials Target Large Addressable Markets Non-Small Cell Lung Cancer (NSCLC) HR+/HER2-/TNBC Breast Cancer Head & Neck Cancer drug market estimated at drug market estimated at drug market estimated at US$ 24 billion US$ 12 billion US$ 3 billion *Efti has FDA Fast Track designation in 1L NSCLC
Slide 13: Lead Indication: First Line Non-Small Cell Lung Cancer (NSCLC)
Lead Indication First Line Non-Small Cell Lung Cancer (NSCLC) ASCO 2022 - Dr. Enriqueta Felip presenting 1L NSCLC SITC 2022 - Dr. Wade Iams presenting 1L NSCLC data from ESMO 2023 - Dr. Enric Carcereny presenting Overall data from TACTI-002/KN-798 in Oral Presentation TACTI-002/KN-798 in Late Breaki
Slide 14: NSCLC Overview
NSCLC Overview o Lung cancer is a leading cause of cancer death1,2 o 80 - 85% of lung cancers are non-small cell lung cancer (NSCLC) o There are ~2.0 million NSCLC diagnoses worldwide annually o Only ~20% of patients respond to immune checkpoint inhibitor (ICI) monotherapy o Despite treatment advanc
Slide 15: PD-L1 Expression Levels and Why They Matter in 1L NSCLC
PD-L1 Expression Levels and Why They Matter in 1L NSCLC Approvals of Chemotherapy-free ICI Therapies in 1L NSCLC by PD-L1 Levels Negative PD-L1 (TPS <1%) Low PD-L1 (TPS 1-49%) High PD-L1 (TPS >50%) • PD-L1 expression as measured by Tumor Proportion Score (TPS) is an FDA approved predictive biomarker
Slide 16: Targeting Entire 1L NSCLC Population Regardless of PD-L1 Status
Targeting Entire 1L NSCLC Population Regardless of PD-L1 Status Strength of clinical data from Efti in combination with KEYTRUDA in high, and particularly negative & low PD-L1 expressing patients, positions this novel combination to potentially establish a new standard of care in 1L NSCLC, one of th
Slide 17: TACTI-002 / KN-798 Trial Overview and Baseline Characteristics
TACTI-002 / KN-798 Trial Overview and Baseline Characteristics Part A: Large Phase II trial (N=114) in metastatic 1st Line non-small cell lung cancer (1L NSCLC) TACTI-002 (Part A) Trial Design TACTI-002 (Part A) in 1L NSCLC • Advanced/metastatic 1L Combination Therapy Monotherapy Primary endpoint: O
Slide 18: Strong Efficacy Data across All PD-L1 Expression Levels in 1L NSCLC
Strong Efficacy Data across All PD-L1 Expression Levels in 1L NSCLC Tumor Response by PD-L1 Expression Level1 All-Comer Negative PD-L1 Low PD-L1 Any PD-L1 High PD-L1 • Strong efficacy across all patients, including negative & low expressors (~75% of patients in TACTI-002), TPS 0-100% TPS <1% TPS 1-4
Slide 19: Benchmarking to Pembrolizumab (KEYTRUDA) Monotherapy
Benchmarking to Pembrolizumab (KEYTRUDA®) Monotherapy mOS mPFS ORR Not Reached 16.5 35.5 55.0 48.3 44.7 11.2 39.1 23.4 20.0 9.3 31.3 16.4 27.3 15.5 6.5 13.4 5.6 16.9 4.2 4.2 Negative Low Any High Negative Low Any High Negative Low Any High PD-L1 PD-L1 PD-L1 PD-L1 PD-L1 PD-L1 PD-L1 PD-L1 PD-L1 PD-L1
Slide 20: Exceptional Durability and Quality of Responses
Exceptional Durability and Quality of Responses 3-Year OS Rate (TPS >1%) 1-Year PFS Rate (TPS >1%) 45.6 46.3 46.8 43 38 • Exceptional 3-year Overall Survival rate of 45.6% in 1L 36 NSCLC, superior to pembrolizumab monotherapy and 33 33.5 34 33 standard-of-care chemo-free & chemo-containing regimens
Slide 21: Differentiated Efficacy in Low & Negative PD-L1 Patients
Differentiated Efficacy in Low & Negative PD-L1 Patients Strong results in low & negative PD-L1 patients who collectively represent ~70% of the 1L NSCLC population mOS mPFS ORR mDOR (TPS 1-49%) (TPS 1-49%) (TPS 1-49%) (TPS 1-49%) 23.4 9.3 Not Reached 44.7 Median Progression-Free Survival (Months) Me
Slide 22: Th1 Biomarker Data Linked to Improved Clinical Outcomes
Th1 Biomarker Data Linked to Improved Clinical Outcomes Significant, sustained increases in CXCL10 & IFN-γ • IFN-γ – After first efti dosing, 86% (6/7) of responders* showed a ≥1.4-fold in TACTI-002 Phase II trial in 1L NSCLC tied to efti’s change and 86% (6/7) of non-responders# had less than a 1.4
Slide 23: Favorable Safety
Favorable Safety Differentiated OS from Efti + Pembrolizumab achieved with a favorable safety profile Drug-related Adverse Therapy in 1L NSCLC TPS >1% Events Leading to Median Overall Survival3 Discontinuation2 Efti + Pembrolizumab 9.6% 35.5 months Pembro + Doublet Chemo (NSQ) 20.5% 23.3 months Pemb
Slide 24: INSIGHT-003: IO-IO-Chemo Combination Trial in 1L NSCLC
INSIGHT-003: IO-IO-Chemo Combination Trial in 1L NSCLC Promising initial efficacy & safety from first-in-human study evaluating Efti + KEYTRUDA + doublet chemo INSIGHT-003 - Investigator-initiated study in first line non-squamous NSCLC • Triple combination well tolerated and appears safe • ~81% of p
Slide 25: Chemotherapy is Additive to KEYTRUDA's Efficacy in 1L NSCLC
Chemotherapy is Additive to KEYTRUDA’s Efficacy in 1L NSCLC KEYTRUDA with Chemotherapy has Superior Efficacy Same Additive Benefit from Chemotherapy to Efti + versus KEYTRUDA Monotherapy in 1L NSCLC KEYTRUDA Observed in INSIGHT-003 trial in 1L NSCLC • Without chemo… Efti + KEYTRUDA has higher ORR, P
Slide 26: Registration Strategy in First line Non-Small Cell Lung Cancer (1L NSCLC)
Registration Strategy in First line Non-Small Cell Lung Cancer (1L NSCLC)
Slide 27: Evolution of Efti + KEYTRUDA in Clinical Trials
Evolution of Efti + KEYTRUDA® in Clinical Trials Growing collaborative effort with MSD over time with positive clinical outcomes across multiple cancers TACTI-mel TACTI-002 TACTI-002 Expansion TACTI-003 TACTI-004 Phase I Phase II Phase II Phase IIb Phase III • First in human study of efti in • 1st c
Slide 28: Treatment Landscape 1st line NSCLC
Treatment Landscape 1st line NSCLC IO-based approaches based on ESMO / NCCN (1) Stage IV NSCLC: Molecular Test Negative (ALK/BRAF/EGFR/ROS1), PS 0-1 Treatment decision usually based on PD-L1 expression TPS ≥50% TPS <1 TPS 1-49% doublet platinum chemotherapy + anti-PD-1 / PD-L1 anti-PD-1 / PD-L1 anti
Slide 29: Immutep & Merck (MSD) to Undertake Phase III Trial in NSCLC
Immutep & Merck (MSD) to Undertake Phase III Trial in NSCLC Opportunity to set a new standard of care across entire NSCLC population regardless of PD-L1 expression Trial Overview: • TACTI-004 will be a 1:1 randomized, double-blind, multinational, controlled clinical study with ~750 patients • Trial
Slide 30: Strong Results in Dual Primary Endpoints Across All PD-L1 Levels Drives Confidence in TACTI-004
Strong Results in Dual Primary Endpoints (OS/PFS) Across All PD-L1 Expression Levels Drives Confidence in TACTI-004 TACTI-004’s large trial design will effectively capture 1L NSCLC patient populations with negative (TPS <1%), low (TPS 1-49%), and high (TPS ≥50%) PD-L1 expression. The strength of eft
Slide 31: Uniquely Positioned Phase III in 1L NSCLC Landscape
Uniquely Positioned Phase III in 1L NSCLC Landscape • KEYTRUDA has revolutionized the treatment landscape in lung cancer, and as a result MSD (Merck) captures between 7 to 8 of every 10 metastatic lung cancer patients today* High Low Squamous PD-L1 PD-L1 • Of KEYTRUDA’s ~US$25 billion in sales in 20
Slide 32: Efti + Anti-PD-1 in Head & Neck Cancer
Efti + Anti-PD-1 in Head & Neck Cancer
Slide 33: Head and Neck Squamous Cell Carcinoma
Head and Neck Squamous Cell Carcinoma Overview: • Head and neck squamous cell carcinoma (HNSCC) encompasses a spectrum of heterogeneous diseases originating in the oral cavity, pharynx, and larynx • HNSCC is a complex disease involving distinct anatomical sites and with varying etiological factors i
Slide 34: Treatment Landscape in 1L HNSCC
Treatment Landscape in 1L HNSCC High unmet need: Recurrent, unresectable, or metastatic disease not amenable to curative RT or surgery • Overall Survival in first line HNSCC is ~12 months PD-L1 positive tumor PD-L1 negative tumor PD-L1 expression: CPS >1 / CPS >20 CPS <1 • PD-L1 expression as measur
Slide 35: TACTI-003 Trial Overview
TACTI-003 Trial Overview Efti + anti-PD-1 therapy has FDA Fast Track designation in recurrent or metastatic 1L HNSCC TACTI-003 / KEYNOTE-C34 Trial Design Pembrolizumab + Efti Cohort A (i.v. 400 mg q6w; s.c 30mg q2w) Randomization PD-L1 CPS >1 1:1 Pembrolizumab Monotherapy N=138 ORR, PFS, OS, PK, (i.
Slide 36: Cohorts A/B: High Response Rates Regardless of PD-L1 Expression
Cohorts A/B: High Response Rates Regardless of PD-L1 Expression ORR (CPS 0-100) High Objective Response Rate (ORR) in TACTI-003 Trial • In the total patient population (N=89) of TACTI-003 from No overlap of Efti + KEYTRUDA (TACTI-003) Cohorts A (CPS ≥1) and B (CPS <1), efti combined with 95% CIs KEY
Slide 37: Cohorts A/B: ORR and DCR across PD-L1 Levels (CPS 0-100)
Cohorts A/B: ORR and DCR across PD-L1 Levels (CPS 0-100) Objective Response Rate (ORR) Disease Control Rate (DCR) 40.0% 90.0% 35.0% 80.0% 35.5% 79.3% 34.5% 34.5% 33.3% 70.0% 30.0% 69.0% 66.7% 60.0% 25.0% 59.3% 58.7% 25.6% 58.1% 50.0% 20.0% 40.0% 45.0% 18.5% 15.0% 16.2% 30.0% 32.4% 10.0% 20.0% 5.0% 1
Slide 38: Cohorts A/B: Favourable Safety Profile
Cohorts A/B: Favourable Safety Profile KEYTRUDA alone Efti + KEYTRUDA Efti + KEYTRUDA Safety Parameter (Cohort A, n=68) (Cohort A, n=69) (Cohort B, n=33) n (%) n (%) n (%) Any TEAR Leading to Discontinuation of Study Treatment 3 (4.4%)1 3 (4.3%)2 3 (9.1%)3 TEAR: Treatment-emergent adverse reaction •
Slide 39: Cohort A: Patients with Any PD-L1 Expression
Cohort A: Patients with Any PD-L1 Expression TACTI-003 Efti + KEYTRUDA KEYTRUDA alone High PD-L1 Expression (CPS >20) 34.5% ORR (N=29) 18.5% ORR (N=27) • Multiple prognostic markers favor the KEYTRUDA mono arm In CPS >20, efti + KEYTRUDA shows strongest outperformance with 87% relative increase. Pat
Slide 40: Cohort A: Superior DOR Compared to Cytotoxic Therapies
Cohort A: Superior DOR Compared to Cytotoxic Therapies Immunotherapies (IO) Not Reached Duration of Response (DOR): “the time from onset of 23.4 response to progression or death due to any reason” median Duration of Response • Immunotherapies engage/train immune system against 18.4 17.1 17.5 Includi
Slide 41: Cohort A: Exploratory Biomarker Analysis
Cohort A: Exploratory Biomarker Analysis • Absolute lymphocyte count (ALC) sees significant increase in E+P group on study (left figure). • ALC increased significantly in responders compared to non- responders (P=0.01) in E+P group and compared to responders (P=0.03) in P alone (right figure). • Inc
Slide 42: Cohort B: Response Rate Among Highest Recorded in CPS <1
Cohort B: Response Rate Among Highest Recorded in CPS <1 RECIST 1.1 iRECIST Best objective response1, n (%) Key Takeaways: N=31 N=31 • ORR of 35.5% and DCR of 58.1%, according to RECIST 1.1 Complete response 3 (9.7) 3 (9.7) • The 35.5% ORR is among the highest recorded for a Partial response 8 (25.8
Slide 43: Cohort B: Tumour Shrinkage in 60% of Patients with CPS <1
Cohort B: Tumour Shrinkage in 60% of Patients with CPS <1 and Excellent Duration of Treatment Change in Tumour Burden ~60% of patients experienced tumour shrinkage and despite deep responses in target lesions, two patients not counted as responders according to RECIST 1.1 (see */** on waterfall plot
Slide 44: Cohort B: Exceptional Results for a Chemo-Free Regimen
Cohort B: Exceptional Results for a Chemo-Free Regimen Objective Complete Response Rate Responses Key takeaways, Cohort B (CPS <1) ORR of 35.5%, DCR of 58.1%, and ~10% complete response rate are exceptional for a chemo-free regimen in this patient population. Data compares favorably to historical
Slide 45: Cohort B: Limited Competition in a Valuable Market
Cohort B: Limited Competition in a Valuable Market Limited competition in CPS <1 • Most IO combinations with anti-PD-1 therapy like KEYTRUDA exclude CPS <1 patients as anti-PD-1 alone is not very active • No chemotherapy-free therapies available for 1L HNSCC patients with CPS <1 • 35.5% ORR among th
Slide 46: Efti + Pembro in 2L Head & Neck Squamous Cell Carcinoma
Efti + Pembro in 2L Head & Neck Squamous Cell Carcinoma Strong, durable efficacy in second line HNSCC (2L HNSCC) TACTI-002/KEYNOTE-798 (Part C): Second Line Head & Neck Squamous Cell Carcinoma (2L HNSCC) TACTI-002 (Part C) Trial Design • Encouraging ORR of 29.7% in ITT population (all-comer - Advanc
Slide 47: Efti + Chemotherapy in Metastatic Breast Cancer (MBC)
Efti + Chemotherapy in Metastatic Breast Cancer (MBC)
Slide 48: AIPAC-001: Efti + Chemo in Randomized Phase IIb in MBC
AIPAC-001: Efti + Chemo in Randomized Phase IIb in MBC AIPAC-001 Study Design AIPAC was conducted in 34 sites across: Belgium, France, Hungary, Poland, Netherlands, UK, and Germany Paclitaxel Efti + paclitaxel Significant correlation between N=112 N=114 CD8+ T cell count Sustained Quality of Life (Q
Slide 49: AIPAC-003 Phase II/III Trial Underway in MBC
AIPAC-003 Phase II/III Trial Underway in MBC AIPAC-003: Active Immunotherapy (Eftilagimod Alfa) and PAClitaxel AIPAC-003: Integrated Phase II/III trial in Metastatic Breast Cancer (MBC) • Trial design incorporates feedback from FDA & EMA and provides risk-balanced approach • Patient population: HR+/
Slide 50: Encouraging Safety and Early Efficacy in AIPAC-003
Encouraging Safety and Early Efficacy in AIPAC-003 50% Response Rate, 100% DCR, and a Confirmed Complete Response at Higher 90 mg Efti Dosing AIPAC-003: Active Immunotherapy (Eftilagimod Alfa) and PAClitaxel Case Study: 35-year-old Woman with Confirmed CR that Continues on Efti Monotherapy* Neo-adju
Slide 51: Additional Oncology Indications and Studies
Additional Oncology Indications and Studies
Slide 52: Efti + Anti-PD-L1 (Avelumab) in Metastatic Urothelial Cancer
Efti + Anti-PD-L1 (Avelumab) in Metastatic Urothelial Cancer INSIGHT-004 – Completed Phase I dose escalation study in INSIGHT-005 – Ongoing Phase I study in metastatic advanced solid tumors* urothelial cancer • Efti in combination with avelumab (BAVENCIO®) safe • Investigator-initiated study evaluat
Slide 53: Soft Tissue Sarcoma: Orphan Disease with High Unmet Need
Soft Tissue Sarcoma: Orphan Disease with High Unmet Need Investigator-initiated trial studying novel triple combination of Efti + Radiotherapy + KEYTRUDA EFTISARC-NEO Phase II Trial Design* Screening Study treatment Follow up • First trial studying efti in neoadjuvant, non-metastatic cancer setting
Slide 54: TACTI-mel: Efti plus KEYTRUDA in Metastatic Melanoma
TACTI-mel: Efti plus KEYTRUDA in Metastatic Melanoma First-in-man study evaluating efti with Patient Case #1 - Pembrolizumab + 1mg Efti (IMP321) Patient Case #3 - Pembrolizumab + 30mg Efti (IMP321) KEYTRUDA® (pembrolizumab) in metastatic • 61-year-old male melanoma patients who had suboptimal patien
Slide 55: Novel Small Molecule Anti-LAG-3 Preclinical Program
Novel Small Molecule Anti-LAG-3 Preclinical Program Immutep aims to develop and commercialize an orally-available small molecule anti-LAG-3 treatment for cancer patients at a lower cost compared with anti-LAG-3 antibodies commercially available or under clinical development today. “Our collaboration
Slide 56: IMP761 & Summary
: @ immutep IMP761 & Summary
Slide 57: Targeting Autoimmune Disease with Immune Checkpoint Agonists
Targeting Autoimmune Disease with Immune Checkpoint Agonists In h ib it o ry re c e p t o r a g o n is t s : t h e fu t u re o f a u t o im m u n e d is e a s e t h e ra p e u t ic s ? “Althoug h c ritic a l q ue stions re m a in, inhib itory re c e p tor a g onists re p re se nt a n und e ra p p re
Slide 58: Competitive Landscape for Checkpoint Agonists
Competitive Landscape for Checkpoint Agonists Company Program Checkpoint / Checkpoint Receptor Preclinical Phase I Phase II Phase III Peresolimab Programmed Cell Death Protein 1 (PD-1) Immune Checkpoint / Checkpoint Receptor Agonists Targeting Autoimmune Diseases Rosnilimab Programmed Cell Death Pro
Slide 59: IMP761: First-in-Class LAG-3 Agonist is a Potential Game-Changer
IMP761: First-in-Class LAG-3 Agonist is a Potential Game-Changer IMP761 is the world’s first immunosuppressive LAG-3 agonist antibody that is designed to address the underlying cause of many autoimmune diseases. This potential game-changer in the treatment landscape received regulatory clearance in
Slide 60: Clinical Development of IMP761
Clinical Development of IMP761 Leading World-Call Research Institute Appointed to Conduct First-in-Human Study Key aspects: • Placebo-controlled, double-blind Phase I (N = 49) • Centre for Human Drug Research (CHDR) has been selected for conduct • First participant enrolled in August 2024 • World-cl
Slide 61: Board and Management
Board and Management Dr Russel Howard Pete Meyers Lis Boyce Anne Anderson Marc Voigt Prof. Frédéric Triebel, MD, PhD Non-Executive Chairman Deputy Chairman Non-Executive Director Non-Executive Director Executive Director & CEO Executive Director, CSO Dr Howard has over 45 years’ Mr Meyers spent 18 y
Slide 62: Outlook
Outlook Milestones & Catalysts Ahead • Non-Small Cell Lung Cancer – TACTI-004 preparations for study start with FPI in late 2024 / early 2025 • Non-Small Cell Lung Cancer – Update from triple combo INSIGHT-003 trial • Head and Neck Squamous Cell Carcinoma – Additional data will be presented in H2 CY
Slide 63: Thank You
: =) Immutep Thank You