Immutep Ltd · ASX:IMM
Immutep — Non-Small Cell Cancer Drug Development Summit 2022
27 slides from Immutep's conference presentation, Sep 22, 2022
Slide 1: Soluble LAG-3 Protein (Eftilagimod Alpha) with Anti-PD-1: Phase II Results in NSCLC
A Soluble LAG-3 Protein (Eftilagimod Alpha) with an Anti-PD-1 Antibody (Pembrolizumab): Results of a Phase II Study in NSCLC Frédéric Triebel MD, PhD Non-Small Cell Cancer Drug Development Summit nd Boston, September 22 2022
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: What is LAG-3?
9 o Immutep What is LAG-3?
Slide 4: Lymphocyte Activation Gene-3 (LAG-3 or CD223)
Lymphocyte Activation Gene-3 (LAG-3 or CD223) Genomic LAG-3 1 kb ATG TGA CD4 LAG-3 NH2 NH 2 L V V C C C Tm Cyt S S V S V S S S C2 S C2 S • 4-IgSF domain transmembrane proteins. S S V S C2 S S S • Same genomic organization C2 S C2 S (intron in D1, duplication event D1D2 vs D3D4). • Close proximity on
Slide 5: Proposed evolutionary pattern for LAG-3/CD4
Proposed evolutionary pattern for LAG-3/CD4 • Duplication of a 2-IgSF domain ancestor • The LAG-3/CD4 subfamily has evolved like the CTLA-4/CD28 subfamily: one inhibitory and one stimulatory receptor modulating TCR signaling • A yin/yang modulatory machinery on T cells LAG-3 CD4 Co-inhibitory Co-sti
Slide 6: LAG-3/MHC-II interaction is a Clinically Validated Therapeutic Target
LAG-3/MHC-II interaction is a Clinically Validated Therapeutic Target Central to Immune Activation LAG-3, an immune checkpoint, is widely expressed on tumor infiltrating lymphocytes (TILs) and cytotoxic T cells, and interacts with MHC class II molecules on APCs LAG-3 / MHC Class II Interaction Posit
Slide 7: Eftilagimod Alpha (efti or IMP321)
Eftilagimod Alpha (efti or IMP321)
Slide 8: Eftilagimod Alpha (efti / IMP321)
Eftilagimod Alpha (efti / IMP321) Efti is a soluble recombinant fusion protein consisting of the Fc portion of a human antibody and the four extracellular domains of human LAG-3 VL Soluble LAG-3 (natural sequence) VH CL D4 D3 D2 D1 CH1 Hinge CH2 CH3 MHC II binding site D1 IMP321 Human IgG1 “LAG-3Ig”
Slide 9: Two endogenous non-TLR ligands that induce DC maturation and migration
Two endogenous non-TLR ligands (sLAG-3 and sCD40L) that induce DC maturation and migration Peripheral tissues Maturation & Lymphoid organs Migration T-cell Mature DC efti Immature DC Th Th1 Pathogens Inflammation CD8 CTL T-cell proliferation sCD40L CD80 + + CD86 + + CD40 + + CD80 + CD86 + CD40+ MHC
Slide 10: Efti: Mechanism of Action (MoA)
Efti: Mechanism of Action (MoA) Efti’s unique agonistic MoA leads to T cell expansion and proliferation → “Pushing the gas pedal” on the immune response! Efti Efti binds to MHC class II on APC DC / monocyte activation induced Leads to T cell expansion and proliferation Notes: 10 https://www.youtube.
Slide 11: Synergistic benefit of APC activation in combination with ICI in NSQ NSCLC
Synergistic benefit of APC activation in combination with ICI in NSQ NSCLC • Molecules associated with antigen presentation like MHC class II – if enriched in the tumor microenvironment – are predictive for PFS for PD-1 antagonists, but not for chemo. • This holds true irrespective of PD-L1 expressi
Slide 12: Efti is an Innovative LAG-3 IO Product
Efti is an Innovative LAG-3 IO Product Not a Checkpoint Inhibitor • The only APC (MHC II) targeting LAG-3 product candidate currently in development • A unique approach (“turning cold tumors into hot tumors” with LAG-3) • Synergistic with other therapeutic agents and modalities e.g. IO agents and ch
Slide 13: Efti Pharmacodynamic Activity
Efti Pharmacodynamic Activity Pharmacodynamic effects observed in different clinical trials 13
Slide 14: PD Activity in Clinical Trials
PD Activity in Clinical Trials Primary and Secondary Target Cells of efti Additional Biomarkers • Increase of soluble factors of type-1 immune response → IFN-g • Increase of IFN-induced chemokines → CXCL10 Key factors for T cell infiltration and generation of „hot“ tumor microenvironment Reschke & G
Slide 15: PD Activity in Clinical Trials
PD Activity in Clinical Trials On Primary Target Cells CD16 expression(1) Monocyte activation marker expression(2) Pre-efti dose 1 Post-efti dose 1 Monocytes increase their activation marker expression following efti administration Notes: Blood sample collected pre-efti and 48h-post efti. Ex vivo ex
Slide 16: PD Activity in Clinical Trials
PD Activity in Clinical Trials On Primary Target Cells: Increased Activation Markers (1) Blood samples collected pre-Pac (pre-Paclitaxel in AIPAC), pre-efti and 24h and 48h-post-efti at Cycle 1 (n=14) and Cycle 6 (n=9). Ex vivo expression of activation markers on monocytes, shown as mean of fold cha
Slide 17: Pharmacodynamic Activity
Pharmacodynamic Activity Long-term, significant increase of target cell numbers vs. placebo PD biomarkers such as monocytes, activated CD4 and CD8 T cells and CXCL10 (IP10) were assessed by flow cytometry at a central lab. ALC measured locally at clinical sites. Blood sampling schedule: always prior
Slide 18: Efti + anti-PD-1 Combination TACTI-002
Efti + anti-PD-1 Combination TACTI-002 “Two ACTive Immunotherapies”
Slide 19: Key Clinical Trials
Key Clinical Trials TACTI-002 (Phase II) design & status TACTI-002: Two ACTive Immunotherapeutics in NSCLC and HNSCC UNSELECTED FOR PD-L1 In collaboration with PART A: S 1ST LINE MET. NSCLC C R PART B: COMBINED E ORR, PFS, OS, PK, 2ND LINE MET. NSCLC, IMMUNOTHERAPY E PEMBROLIZUMAB + EFTI FOR 12 biom
Slide 20: TACTI-002 Results: Baseline Characteristics
TACTI-002 Results(*) st 1 line NSCLC (Part A) - Baseline Characteristics • PD-L1 distribution as expected (~70% with PD-L1 TPS < 50% expression) → PD-L1 all comer trial • 114 1st line NSCLC patients enrolled with expected disease characteristics Baseline parameters Part A (N=114) Age, median (range)
Slide 21: Clinical Data Exposure and Safety Overview
Clinical Data Safety Profile: efti + pembrolizumab(1) Exposure and Safety Overview General safety parameters TACTI-002 Part A (1st line NSCLC) N=114 Summary n (%) • ISS database informing on the administration of efti 30 mg in combination with pembrolizumab Any AR 80 (70.2 %) comprised 110 subjects
Slide 22: TACTI-002 Results: Primary Objective (ORR > 35%) achieved
TACTI-002 Results st (1) 1 line NSCLC (Part A) - ORR ORR – PD-L1 all comer iRECIST RECIST 1.1 • ORR (iRECIST - primary Response(5) endpoint) of 38.6% in the ITT n (%), N=114 n (%), N=114 • RECIST 1.1 comparable with Complete Response 2 (1.8) 2 (1.8) 37.7% Partial Response 42 (36.8) 41 (36.0) • ORR o
Slide 23: TACTI-002 Results: ORR by PD-L1 status
TACTI-002 Results st (*) 1 line NSCLC (Part A) - ORR • ORR (iRECIST) by PD-L1 (central only): ▪ 28.1% in PD-L1 negative ▪ 41.7% in PD-L1 1-49% Favourable ORR in ▪ 52.6% in PD-L1 ≥ 50% PD-L1 low and PD-L1 ▪ 45.5% in PD-L1 ≥ 1% negative tumors • DCR (iRECIST) with a range of 68.8-78.9% across all PD-L
Slide 24: TACTI-002 Results: Waterfall & Spider Plot
TACTI-002 Results st (*) 1 line NSCLC (Part A) - Waterfall & Spider Plot 100 75 • 2 complete responses and 19.4% of patients with a target lesion decrease ≥ 50% Best % change from baseline 50 25 • 68/103 (66.0%) of patients with a post-baseline 0 assessment had a decrease in target lesions -25 -50 1
Slide 25: TACTI-002 Results: PFS
TACTI-002 Results st (*) 1 line NSCLC (Part A) - PFS PFS ITT population (N=114) (*) PFS by PD-L1 status (N=108)(*, 1) • Interim median PFS(*) in the ITT (unselected for • Interim median PFS(1) in PD-L1 ≥ 1% was 8.4 PD-L1) was 6.9 (95% CI: 4.4-8.4) months (95% CI: 6.1-14.0) months and 11.8 (5.5-16.8)
Slide 26: Summary & Conclusion
Summary & Conclusion • ORR (iRECIST) of 38.6% (95% CI: 29.6-48.2) in 1 line NSCLC patients (ITT) st unselected for PD-L1. • Comparable results acc. to RECIST 1.1 for ORR with 37.7% (95% CI: 28.8-48.3) in the ITT. • Promising ORR compared to historical control (KN-0421). • Responses are deep and dura
Slide 27: Thank You
Thank You Frédéric Triebel MD, PhD Non-Small Cell Cancer Drug Development Summit nd Boston, September 22 2022
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