Slide 1: Eftilagimod Alpha Clinical Development Update and New Data from Ongoing Melanoma Study
For personal use only Eftilagimod Alpha Clinical Development Update and New Data from Ongoing Melanoma Study Date & Time: Wednesday, April 3, 2019, 7:45am Australian Eastern Standard Time Tuesday, April 2, 2019, 4:45pm US Eastern Daylight Time Register: Interested investors can register via a link t
Slide 2: Notice: Forward Looking Statements
Notice: Forward Looking Statements For personal use only 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
Slide 3: LAG-3 Overview
3 For personal use only LAG-3 Overview
Slide 4: Evolution of Checkpoint Therapies
Evolution of Checkpoint Therapies LAG-3 has the potential to be the next meaningful checkpoint target… For personal use only Evolution of Immuno-Oncology Therapies Opdivo/ anti-LAG-3 Combination(1) Opdivo/ Yervoy combination Yervoy Keytruda/ chemo Keytruda combination 2011 `12 `13 `14 `15 `16 `17 `1
Slide 5: LAG-3 Therapeutic Landscape Overview
LAG-3 Therapeutic Landscape Overview For personal use only Immutep is the leader in developing LAG-3 modulating therapeutics Program Eftilagimod Alpha (IMP321) LAG525 (IMP701) GSK2831781 (IMP731) Relatlimab Company BMS Late stage 1 1 trial trial 2 trials Phase 2 1 trial 3trials 1 trial 12 trials Pha
Slide 6: Eftilagimod Alpha (Efti, IMP321)
For personal use only Eftilagimod Alpha (Efti, IMP321) 6
Slide 7: Eftilagimod Alpha structure
Eftilagimod Alpha For personal use only Efti is a soluble recombinant fusion protein consisting of the Fc portion of a human antibody and the four extracellular domains of LAG-3 VL VH D4 D3 D2 D1 CL CH1 Hinge Soluble LAG-3 CH2 MHC II binding site CH3 D1 Human IgG1 IMP321 D2 “LAG-3Ig” D3 D4 Hinge CH2
Slide 8: Innovative LAG-3 IO Product Candidate
Efti - Innovative LAG-3 IO Product Candidate For personal use only • Only APC targeting LAG-3 product candidate currently in clinical development • A unique approach (“turning cold tumors into hot tumors” with LAG-3) • Synergistic with other therapeutic agents and modalities e.g. IO agents, chemothe
Slide 9: Eftilagimod Alpha Clinical Trials
Eftilagimod Alpha Clinical Trials* For personal use only Expecting multiple data readouts throughout H2 2019* Program Preclinical Phase I Phase II Late Stage Commercial Oncology Rights/Partners AIPAC (Chemo-IO Combo) Metastatic Breast Cancer 2019 (1) TACTI-002 Global (IO-IO Combo) NSCLC (1st/2nd L.)
Slide 10: Efti Clinical Development Overview
For personal use only Efti Clinical Development Overview 10
Slide 11: Areas of Development
Efti - Areas of Development Multiple Strategies For personal use only Efti has multiple shots on goal in different indications and in different combinations Chemo-immunotherapy IO-IO combination • Exploit the antigen debris from • Increase response rates and durability, chemotherapy with an APC acti
Slide 12: Efti TACTI-mel results
For personal use only Efti TACTI-mel results 12
Slide 13: TACTI-mel – Trial Design
Efti in Melanoma TACTI-mel – Trial Design For personal use only TACTI-mel: Two ACTive Immunotherapeutics in Melanoma Recommended Phase I, multicenter, 24 patients, Efti (IMP321) + Phase II dose, open label, 4 cohorts of 6 patients anti-PD-1 (Keytruda) safety and dose escalation tolerability Other P
Slide 14: TACTI-mel – Safety Part A + B
Efti in Melanoma TACTI-mel – Safety Part A + B For personal use only Efti has a favorable safety profile in combination with pembrolizumab - No DLTs or MTDs and no new safety signals observed Frequent TEAE (selected if ≥ 15 % of pts) Grade 3 / 4 TEAEs and rel. to study treatment Any grade ≥ Grade 3
Slide 15: TACTI-mel – Blood Pharmacodynamics
Efti in Melanoma TACTI-mel – Blood Pharmacodynamics For personal use only Sustained markers of immune response observed Part A Part B Part B IFN-g (not yet available for Part B) Activated CD4 T cells Activated CD8 T cells ** ** ** DR+ CD38+ CD8 T cells (cells/µl) DR+ CD38+ CD4 T cells (cells/µl) [IF
Slide 16: TACTI-mel – Baseline Characteristics
Efti in Melanoma TACTI-mel – Baseline Characteristics For personal use only Patients in very late stage of disease (M1c, elevated LDH, liver metastasis) Baseline Characteristics Part A Part B Overall N = 18 (%) N = 6 (%) N =24 (%) Median Age 67 yrs 61 yrs 62 yrs Sex (f/m) 6 % / 94 % 17 % / 83 % 8 %
Slide 17: TACTI-mel – Results Part A
Efti in Melanoma TACTI-mel – Results Part A For personal use only Majority not responding to pembrolizumab monotherapy → Tumor shrinkage in 56 % incl. 2 pts with disappearance of all target lesions Best Overall Response N = 18 (%) Spider plot* (part A) Waterfall plot* (part A) acc. to irRC (starting
Slide 18: TACTI-mel – Results Part B
Efti in Melanoma TACTI-mel – Results Part B For personal use only Confirmed deep partial responses in 3 (50%) of the pts Treatment of 4 pts ongoing, all over 6 months Spider plot* (part B) Waterfall plot* (part B) Best Overall Response acc. N = 6 (%) to irRC 125 100 % change compared to baseline Bes
Slide 19: TACTI-mel – Results Part B – Single Case
Efti (IMP321) in Melanoma TACTI-mel – Results Part B – Single Case For personal use only July 2018 (baseline) January 2019 (6 months) L L • 69 year old male Lung • Multiple lung, bone, liver and lymph node metastases from melanoma → M1C stage • BRAF wild type • ECOG 1 L L Liver → clear regression of
Slide 20: TACTI-mel – Analysis Parts A+B (1)
Efti in Melanoma TACTI-mel – Analysis Parts A+B (1) For personal use only Overall response rate is 58% and 58% of patients are progression-free 6 months after start of pembrolizumab (1) ORR acc. to irRC N = 24 (%) Waterfall Plot* (part A+B) (C1/D1 analysis)(1) (starting cycle 1 day 1 pembrolizumab)
Slide 21: TACTI-mel – Analysis Parts A+B (2)
Efti in Melanoma TACTI-mel – Analysis Parts A+B (2) For personal use only Swimmerplot parts A + B (starting cycle 1 day 1 pembrolizumab) Conclusion BOR (C1D1) irPR irPR irPR • No treatment termination due irSD to safety issues of the irCR irPR combination irPR irPR irPR • 5+ pts on treatment for > 1
Slide 22: Comparison to historical controls
Efti in Melanoma Comparison to historical controls For personal use only How does the data fit in the treatment landscape and in comparison to pembro monotherapy? TACTI-Mel enrolled ipilimumab (ipi) naive and ipi pre-treated patients → Keynote-002 (pre-treated) and Keynote-006 (naive) used for compa
Slide 23: Efti Clinical Development Updates
For personal use only Efti Clinical Development Updates TACTI-002 / INSIGHT-004 /AIPAC 23
Slide 24: TACTI-002 (Phase II)
Efti - Clinical Development TACTI-002 (Phase II) For personal use only TACTI-002: Two ACTive Immunotherapeutics in different indications Simon’s 2 stage Efti (IMP321) + Pembrolizumab Phase II, multi- ORR, PFS, OS, PK, design; 3 indications; (Keytruda) for 12 months + 12 national (EU + US Biomarker;
Slide 25: INSIGHT-004 (Phase I)
Efti - Clinical Development INSIGHT-004 (Phase I) For personal use only INSIGHT-004 – Dose escalation of efti in combination with avelumab Dose escalation, Efti (IMP321) + Avelumab Phase I, solid tumors, 2 (Bavenico) for 6 months + 6 monocenter DE, RP2D, Safety, ORR, cohorts of 6 pts each months av
Slide 26: AIPAC
Efti - Clinical Development AIPAC For personal use only AIPAC: Active Immunotherapy PAClitaxel in MBC Arm 1, 113 patients: Phase IIb, Safety-run in, paclitaxel + IMP321 multinational, Run-in: RP2D 15 (6+9) patients, Stage 2 randomized, Stage 2: Efficacy (PFS) 2 cohorts Arm 2, 113 patients: double-bl
Slide 27: Potential Target Markets
Efti - Areas of Development Potential Target Markets For personal use only Treatment Landscape MBC (Before AIPAC) Treatment Landscape (Today) HER2-negative / HR positive MBC (~65 % of all breast cancers) MBC patients are heavier pre- treated → chemotherapy may be ~ 40-66 % 1-2 lines of 66 %(2) endoc
Slide 28: Summary
Efti Summary For personal use only ✓ Favorable safety profile ✓ Sustained systemic immune response ✓ Encouraging efficacy data in different settings ✓ Clinical trials with industry leading collaborators ✓ Potentially low cost of goods ✓ Potential pipeline in a product ✓ Late stage clinical developme
Slide 29: Thank you!
29 For personal use only Thank you!