Immutep Ltd · ASX:IMM

Immutep — Third Annual Advances in Immuno-oncology Congress 2018

37 slides from Immutep's conference presentation, May 25, 2018

  1. Slide 1: Two ACTive Immunotherapies In Melanoma (TACTI-mel): Phase I Results

    Two ACTive Immunotherapies In Melanoma (TACTI-mel): Results Of A Phase I Trial With Metastatic Melanoma Patients Treated With A Soluble LAG-3 Receptor (LAG-3lg Or Eftilagimod Alpha) As An Antigen Presenting (APC) Activator Combined With Pembrolizumab Frédéric Triebel MD, PhD Third Annual Advances in

  2. 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

  3. Slide 3: Explanatory Note for Readers

    EXPLANATORY NOTE FOR READERS This presentation contains the following information (excerpt): • Very favorable safety profile no MTD (maximum tolerated dose) reached; efti based combination therapies are feasible and safe • Encouraging activity in metastatic breast cancer when combined with paclitaxe

  4. 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 NH 2 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 • Same genomic organization C2 S S C2 S S (intron in D1, duplication event D1D2 vs D3D4) • Close proximity on

  5. Slide 5: Proposed Evolutionary Pattern for LAG-3/CD4

    Proposed Evolutionary Pattern for LAG-3/CD4 • Duplication of a two Ig domain ancestor • The LAG-3/CD4 subfamily has evolved like the CTLA-4/CD28 subfamily: one inhibitory and one stimulatory receptor modulating TCR signaling Co-inhibitory Co-stimulatory 5

  6. Slide 6: Timeline of immune checkpoint discovery

    Timeline of immune checkpoint discovery. 6

  7. Slide 7: 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 CTLA-4 (targeted by Yervoy®) and PD-1 (targeted by Keytruda®) → Positive LAG-3/ MHC class II interaction

  8. Slide 8: LAG-3 Competitive Landscape

    LAG-3 Competitive Landscape 35 8,000 30 7,000 30 Total Estimated Patients in LAG-3 Trials 6,000 Number of LAG-3 Clinical Trials 6,747 25 5,000 20 19 4,941 4,000 15 14 4,262 3,000 10 7 2,000 5 4 2,780 1,000 1 1,539 1,000 0 0 2013 2014 2015 2016 2017 2018 No. Clinical Trials* Total Est. Patients* Sour

  9. Slide 9: LAG-3 Therapeutic Landscape Overview

    LAG-3 Therapeutic Landscape Overview Immutep is the leader in developing LAG-3 modulating therapeutics Total Estimated Program Company Preclinical Phase I Phase I/ II Phase II Phase IIb Phase II/III Patients Eftilagimod Alpha Immutep(1), (2) 385 LAG525 Novartis(3), (4) 961 Relatlimab BMS(4), (5) 4,0

  10. Slide 10: Targeting LAG-3 May Lead to Multiple Therapeutics in Numerous Indications

    Targeting LAG-3 May Lead to Multiple Therapeutics in Numerous Indications 10

  11. Slide 11: Eftilagimod Alpha: Innovative LAG-3 IO Product Candidate

    Eftilagimod Alpha: 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 LAG-3) • Synergistic with other I-O agents “PUSHING THE ACCELERATOR ON IMMUNE RESPONSES” “RELEASING THE BR

  12. Slide 12: Lead Program Eftilagimod Alpha (IMP321)

    Lead Program Eftilagimod Alpha (IMP321)

  13. Slide 13: Eftilagimod alpha (IMP321) Soluble dimeric recombinant form of LAG-3Ig

    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

  14. Slide 14: Eftilagimod alpha (IMP321) MoA

    Eftilagimod alpha (IMP321) MoA • Highly efficacious in multiple animal models of cancer and infectious disease • Shown to be safe, non-immunogenic and efficacious in human 14

  15. Slide 15: 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

  16. Slide 16: Induces Better CD8 Tc1 Differentiation Than sCD40L or TLR Agonists

    Eftilagimod alpha (IMP321) Induces Better CD8 Tc1 Differentiation Than sCD40L or TLR Agonists 2.50 IL-2+IFN+TNF+ ➢ Human blood lymphocytes are analyzed in a 16 hr ex IL-2+IFN+ vivo assay 2.00 IL-2+TNF+ IFN+TNF+ % of CD8+ cells 1.50 ➢ Intracellular staining of CD8 T cells IL-2+ 1.00 TNF+ Only IMP321

  17. Slide 17: APC Activation Turns on the Heat on a Cold Tumor

    APC Activation Turns on the Heat on a Cold Tumor (Breast Cancer Liver Metastasis) CD3 (x5) CD3 (x10) Massive infiltration of T cells (IHC) around the tumor nodules. Some CD3 T cells infiltrating the tumor nodules. Hemihepatectomy for single residual tumor mass after 13 IMP321 s.c. injections in a MB

  18. Slide 18: Clinical Development Eftilagimod Alpha (IMP321)

    Clinical Development Eftilagimod Alpha (IMP321)

  19. Slide 19: Eftilagimod alpha – Potential Applications

    Eftilagimod alpha – Potential Applications Potential combination therapy strategies: • Chemo-immunotherapy in various cancer indications ➢ Combination therapy with active agents such as Taxanes (e.g. Paclitaxel), anthracyclines, alkylating agents, anti-metabolites, vincas… • I-O combination in vario

  20. Slide 20: Eftilagimod alpha in MBC

    Eftilagimod alpha in MBC AIPAC (Pivotal Phase IIb) Arm 1, 113 patients: Safety-run in, paclitaxel + IMP321 Phase IIb, Safety Run-in: recommended 15 (6+9) patients, Stage 2 multinational, Phase IIb dose (RP2D) Stage 2 cohorts randomized, double- 2: Efficacy (PFS) Arm 2, 113 patients: blind paclitaxel

  21. Slide 21: Eftilagimod alpha – Preliminary Efficacy

    Eftilagimod alpha – Preliminary Efficacy MBC – 1st line chemotherapy + IMP321 P005 – phase I AIPAC (P011) – phase I trial Response parameter Paclitaxel + IMP321 (n = 15) 0/15 (0 %) Complete Response (CR) 7/15 (47 %) Partial Response (PR) 6/15 (40 %) Stable Disease (SD) 2/15 (13 %) Progressive Diseas

  22. Slide 22: Pharmacodynamic Results on Primary Target Cells

    Eftilagimod alpha – Clinical Overview Pharmacodynamic Results on Primary Target Cells A B *** *** ** ** Dendritic cells (cells/µl of blood) Monocytes (cells/µl of blood) Baseline 3 months 6 months Baseline 3 months 6 months IMP321 leads to sustainable (> 6 months) increase of pre-dose APCs (run-in p

  23. Slide 23: Pharmacodynamic Results on Primary Target Cells

    Eftilagimod alpha – Clinical Overview (cont.) Pharmacodynamic Results on Primary Target Cells A B IMP321 activates APCs (run-in phase, AIPAC trial). 23

  24. Slide 24: Pharmacodynamic Results on Secondary Target Cells

    Eftilagimod alpha – Clinical Overview (cont.) Pharmacodynamic Results on Secondary Target Cells A ** B * CD8 T cells (cells/µl of blood) Baseline 3 months 6 months Baseline 3 months 6 months IMP321 leads to sustainable (> 6 months) increase of pre-dose effector CD8 T cells and NK cells (run-in phase

  25. Slide 25: Pharmacodynamic Results on Secondary Target Cells

    Eftilagimod alpha – Clinical Overview (cont.) Pharmacodynamic Results on Secondary Target Cells IMP321 leads to sustainable (> 6 months) increase of pre-dose activated (HLA-DR + CD38+) CD4 and CD8 T cells (run-in phase, AIPAC trial). 25

  26. Slide 26: Improved Th1 status

    Eftilagimod alpha – Clinical Overview (cont.) Improved Th1 status *** *** * * * * [IFN-γ] (pg/ml) Pre Post Pre Post Cycle 1 Cycle 6 IMP321 leads to an improved pre-dose Th1 status (IFN, IP-10 not shown) (run-in phase, AIPAC trial), a phenomenon not seen with therapeutic anti-PD-1 mAbs. 26

  27. Slide 27: Eftilagimod Alpha INSIGHT Clinical Trial Investigator Initiated Trial

    Eftilagimod Alpha INSIGHT Clinical Trial Investigator Initiated Trial Eftilagimod Alpha in i.t. and i.p. application • Prof. Al-Batran, IKF, Frankfurt, Germany • Population: 38 pts (9 pts per stratum A and B, 20 pts in stratum C) with advanced solid tumors w/o standard treatment options • Objectives

  28. Slide 28: Eftilagimod Alpha/Pembrolizumab Combination

    Eftilagimod Alpha/Pembrolizumab Combination

  29. Slide 29: Three Groups of Patients Responding to anti-PD-1

    Three Groups of Patients Responding to anti-PD-1 (IFN- signature) ➢ A- Inflamed responders – respond to anti-PD-1 ➢ B- Inflamed non-responders (some infiltrates in the tumor margins but no response) ➢ C- Non inflamed. “Cold tumor” with no response Optimal checkpoint combos will target groups B and

  30. Slide 30: New rationale for combining eftilagimod alpha to pembrolizumab

    New rationale for combining eftilagimod alpha to pembrolizumab Problem: melanoma patients with low Solution: efti (IMP321) increases monocyte numbers at base line are not monocyte numbers in cancer responding well to anti-PD-1 therapy. patients 60 1.00 50 Classical monocytes % Overall survival 0.75

  31. Slide 31: TACTI-mel (IO combination) – 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, IMP321 + anti-PD-1 Phase II dose, open label, 4 cohorts of 6 patients (Keytruda) safety and dose escalation tolerability Primary R

  32. Slide 32: TACTI-mel (IO combination) – details part A

    Efti (IMP321) in Melanoma TACTI-mel (IO combination) – details part A Study Scheme Part A: irRC…Immune-Related Response Criteria, PFS- progression free survival, FU – follow-up Patient population Part A: • Patients with unresectable or metastatic melanoma with asymptomatic progression or suboptimal

  33. Slide 33: TACTI-mel – results after start of combo (1)

    Efti (IMP321) in Melanoma TACTI-mel (IO combination) – results after start of combo (1) Baseline Characteristics N = 18 (%) Waterfall plot starting from cycle 5 of pembrolizumab Visceral Disease 15 (83 %) Pre-treated with 4 (22 %) BRAF/MEK/ipilimumab irPD/irSD to pembrolizumab after 12 (67 %) 3 cycl

  34. Slide 34: TACTI-mel – results after start of combo (2)

    Efti (IMP321) in Melanoma TACTI-mel (IO combination) – results after start of combo (2) Spiderplot - cohort 1-3 (n=18) – May 2018 Conclusion % c h a n g e c o m p a re d to s ta r t o f c o m b o • Complete responses of target lesions 800 400 occurred after 11 and 18 months --> 100 n =18 Long lastin

  35. Slide 35: TACTI-mel – single case at 1 mg efti

    Efti (IMP321) in Melanoma TACTI-mel (IO combination) – single case at 1 mg efti Efficacy: metastatic melanoma pre-pembro week 9 (pembro) week 25 (combo) week 37 (combo) R L R L R L R L Tumor progression week 49 (Pembro mono) week 64 (PFS-FU) R L R L All lesions disappeared → CR (confirmed) patient w

  36. Slide 36: TACTI-mel – single case at 6 mg efti

    Efti (IMP321) in Melanoma TACTI-mel (IO combination) – single case at 6 mg efti Sum of target lesions (TL) acc to irRC Pre pembro Target lesion: chest wall Σ TL (irRC) 100 25 25 25 0 mm² mm² mm² mm² mm² 9 months after start of combo In % 0% -75 % -75 % -75 % -100 % Response NA irPR irPR irPR irPR •

  37. Slide 37: Thank you

    Thank you Frédéric Triebel MD, PhD Third Annual Advances in Immuno-oncology Congress London, May 25, 2018

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