Immutep Ltd · ASX:IMM
Immutep — World Immunotherapy Congress USA 2019
21 slides from Immutep's conference presentation, Mar 5, 2019
Slide 1: Two ACTive Immunotherapies (TACTI): Results of a Phase I trial with metastatic melanoma patients
Two ACTive Immunotherapies (TACTI): Results of a Phase I trial with metastatic melanoma patients Frédéric Triebel MD, PhD World Immunotherapy Congress USA San Diego, March 5, 2019
Slide 2: Notice: Forward Looking Statements
Notice: 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 cla
Slide 3: Evolution of Checkpoint Therapies
Evolution of Checkpoint Therapies LAG-3 has the potential to be the next meaningful checkpoint target… Timeline of Immune Checkpoint Discovery Evolution of Immuno-Oncology Therapies Opdivo/anti-LAG-3 Combination(1) Opdivo/ Yervoy combination Yervoy Keytruda/ chemo Keytruda combination 2011 `12 `13 `
Slide 4: Increasing Clinical Trials Targeting LAG-3
Increasing Clinical Trials Targeting LAG-3 Industry increasingly deploying resources to development of LAG-3 therapeutics 50 14,000 47 45 43 11,610 12,000 Total Estimated Patients in LAG-3 Trials 40 10,906 Number of LAG-3 Clinical Trials 35 10,000 30 8,000 25 21 6,000 20 15 15 5,863 4,000 7 10 4 4,8
Slide 5: LAG-3 as a Therapeutic Target
LAG-3 as a Therapeutic Target • LAG-3 is widely expressed on tumor infiltrating lymphocytes (TILs) and cytotoxic T cells Prime target for an immune checkpoint blocker • Functionally similar to PD-1 on T cells (arrow on the right) Positive LAG-3/ MHC class II interaction regulation of antigen pre
Slide 6: Targeting LAG-3/MHC II May Lead to Multiple Therapeutics in Numerous Indications
Targeting LAG-3/MHC II May Lead to Multiple Therapeutics in Numerous Indications 6
Slide 7: Lead Program Eftilagimod Alpha (IMP321)
L ead Program Eftilagimod Alpha (IMP321)
Slide 8: Eftilagimod alpha (IMP321)
Eftilagimod alpha (IMP321) Soluble dimeric recombinant form of LAG-3Ig (fusion protein) 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 CH3 • Soluble recombinant form of LAG-3 • Human fusion protein • Dimeric, very stable, hi
Slide 9: Efti - Innovative LAG-3 IO Product Candidate
Efti - Innovative LAG-3 IO Product Candidate • The only APC targeting LAG-3 product currently in clinical development • A unique approach (“turning cold tumors into hot tumors” with an MHC II agonist) • Synergistic with other IO agents “PUSHING THE ACCELERATOR ON IMMUNE RESPONSES” “RELEASING THE BRA
Slide 10: Rationale for Combining efti (IMP321) with Chemotherapy or Anti-PD-1 mAb
Rationale for Combining efti (IMP321) with Chemotherapy or Anti-PD-1 mAb Therapeutic interventions leading to increased T cell responses in cancer. The Cancer Immunity Cycle. Adapted from Chen and Mellman (1). 10
Slide 11: Efti (IMP321) - Areas of development
Efti (IMP321) - Areas of development Multiple strategies Active clinical trials • Chemo-immunotherapy AIPAC Exploit the antigen debris from chemotherapy with an APC MBC study in Chinese pts activator Combination therapy with active agents such as (EOC) Taxanes (e.g. Paclitaxel) • IO-IO combinati
Slide 12: Clinical Development Eftilagimod Alpha (IMP321)
Clinical Development Eftilagimod Alpha (IMP321)
Slide 13: IO Therapy Oncology Response Rates
IO Therapy Oncology Response Rates Approximately 70-80% of patients do no respond to anti-PD1 monotherapy. How can we enable more efficacious T-cell responses? • Immunogenic cell death to liberate/uncover tumor antigens • Cross-presentation of those antigens • Recruitment of T cells into the tumor m
Slide 14: Efti (IMP321) in Melanoma: TACTI-mel Trial Design
Efti (IMP321) in Melanoma TACTI-mel (IO combination) – Trial Design 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 Pr
Slide 15: TACTI-mel (IO combination) – Part A and Part B
Efti (IMP321) in Melanoma TACTI-mel (IO combination) – Part A and Part B Study Scheme Part A: Study Scheme Part B: irRC…Immune-Related Response Criteria, PFS- progression free survival, FU – follow-up Patient population Part A: Patient population Part B: • Patients with unresectable or metastatic •
Slide 16: TACTI-mel Results after Start of Combo (part A)
Efti (IMP321) in Melanoma TACTI-mel (IO combination) – Results after Start of Combo (part A) Spider plot* (starting with Waterfall plot* (starting with Baseline Characteristics N = 18 (%) cycle 5 of pembrolizumab) cycle 5 of pembrolizumab) ECOG 1 / 0 22 % / 78 % Elevated LDH 7 (39%) Metastasis stage
Slide 17: TACTI-mel (IO combination) – Results part B
Efti (IMP321) in Melanoma TACTI-mel (IO combination) – Results part B Baseline Characteristics N = 6 (%) Spider plot* (part B) Waterfall plot* (part B) ECOG (0/1) 3 (50 %) / 3 (50 %) % change compared to baseline Sex (f/m) 1 (13 %) / 5 (83 %) Elevated LDH 5 (83%) Metastasis stage M1c 6 (100 %) Best
Slide 18: TACTI-mel – Blood Pharmacodynamics
Efti (IMP321) in Melanoma TACTI-mel (IO combination) – Blood Pharmacodynamics 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) [IFN-g] (pg/ml) Baseline 3 months 6 months Ba
Slide 19: TACTI-mel part B: Single Case
TACTI-mel part B: Single Case July 2018 (baseline) January 2019 (6 months) L L • 69 year old male • Multiple lung, bone, liver and lymph node metatases from melanoma M1C stage • BRAF wild type • ECOG 1 L L clear regression of lung and liver metastases treatment continues (6+ months) 19
Slide 20: TACTI-002 Trial Design
TACTI-002 Trial Design An umbrella trial: Two ACTive Immunotherapeutics in different indications Efti (IMP321) + Pembrolizumab Phase II, multi- Response rate; PFS, OS, Simon’s 2 stage; 3 (Keytruda) for 12 months + national (EU + US PK, Biomarker; Safety and indications; up to max. of 12 months + AU
Slide 21: Thank you
Thank you Frédéric Triebel MD, PhD World Immunotherapy Congres s US A S an Diego, March 5, 2019