Immutep Ltd · ASX:IMM

Immutep — 13th Annual Advanced Therapy and Regenerative Medicine Congress 2018

26 slides from Immutep's conference presentation, May 17, 2018

  1. Slide 1: LAG-3: the next immune checkpoint after CTLA-4 and PD-1/PDL-1?

    LAG-3: the next immune checkpoint after CTLA-4 and PD-1/PDL-1? Frédéric Triebel MD, PhD Keynote session: immuno-oncology and strategies to improve patient success WATRMC, London. May 17, 2018

  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: Lymphocyte Activation Gene-3 (LAG-3 or CD223)

    Lymphocyte Activation Gene-3 (LAG-3 or CD223) Genomic LAG-3 1 kb ATG CD4 LAG-3 TGA 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

  4. Slide 4: Timeline of immune checkpoint discovery

    Timeline of immune checkpoint discovery.

  5. 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 CTLA-4 (targeted by Yervoy®) and PD-1 (targeted by Keytruda®)  Positive LAG-3/ MHC class II interaction

  6. Slide 6: Total Estimated Patients in LAG-3 Trials

    LAG-3 Competitive Landscape 35 8,000 30 7,000 30 Total Estimated Patients in LAG-3 Trials 6,747 6,000 Number of LAG-3 Clinical Trials 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 1,000 1,539 0 0 2013 2014 2015 2016 2017 2018 No. Clinical Trials* Total Est. Patients* Sour

  7. Slide 7: 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) 370 LAG525 Novartis(3), (4) 961 Relatlimab BMS(4), (5) 4,0

  8. Slide 8: Targeting LAG-3 May Lead to Multiple Therapeutics in Numerous Indications

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

  9. Slide 9: 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

  10. Slide 10: Lead Program Eftilagimod Alpha (IMP321)

    Lead Program Eftilagimod Alpha (IMP321)

  11. Slide 11: Eftilagimod alpha (IMP321)

    Eftilagimod alpha (IMP321) VL VH D4 D3 D2 D1 CL CH1 Hinge Soluble LAG-3 CH2 CH3 Human IgG1 IMP321 “LAG-3Ig” Hinge CH2 CH3 • Soluble recombinant form of LAG-3 • Human fusion protein • Dimeric, very stable, high affinity for DC • Antigen presenting cell (APC) activator • Unique and first-in-class 11

  12. Slide 12: Eftilagimod alpha (IMP321)

    Eftilagimod alpha (IMP321) Soluble dimeric recombinant form of LAG-3Ig (fusion protein) • Highly efficacious in multiple animal models of cancer and infectious disease • Shown to be safe, non-immunogenic and efficacious in human 12

  13. 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

  14. Slide 14: APC Activation Turns on the Heat on a Cold Tumor

    APC Activation Turns on the Heat on a Cold Tumor (Breast Cancer) 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 MBC patient treated

  15. Slide 15: Clinical Development Eftilagimod Alpha (IMP321)

    Clinical Development Eftilagimod Alpha (IMP321)

  16. Slide 16: 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 vari

  17. Slide 17: 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

  18. Slide 18: Eftilagimod alpha – Clinical Overview: 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

  19. Slide 19: Eftilagimod alpha – Clinical Overview (cont.): 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

  20. Slide 20: Eftilagimod alpha – Clinical Overview (cont.): 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. 20

  21. Slide 21: Eftilagimod Alpha INSIGHT Clinical 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: 18 pts (9 per stratum) with advanced solid tumors w/o standard treatment options • Objectives: Recommended Phase II dose, PD e

  22. Slide 22: Eftilagimod Alpha/Pembrolizumab Combination

    Eftilagimod Alpha/Pembrolizumab Combination

  23. Slide 23: Eftilagimod Alpha in Melanoma TACTI-mel

    Eftilagimod Alpha in Melanoma TACTI-mel (IO combination) TACTI-mel trial: Two ACTive Immunotherapeutics in melanoma 24 patients, 4 Phase I, multicenter, Recommended IMP321 + anti-PD-1 Phase II dose cohorts of 6 open label, (Keytruda) Safety and patients dose escalation tolerability Primary Recommen

  24. Slide 24: TACTImel – melanoma Phase I study Efficacy Update

    TACTImel – melanoma Phase I study Efficacy Update Cohort 1 +2 Parameter Patients % Disease Control Rate 8/12 66 % Overall Response Rate 4/12 33 % Patients with decrease 7/12 58 % in tumor burden

  25. Slide 25: Eftilagimod Alpha TACTI-mel: Patient 02-01 Preliminary Results

    Eftilagimod Alpha TACTI-mel Patient 02-01 (1mg): Preliminary Results Efficacy: metastatic melanoma irPD All lesions disappeared  CR (confirmed) patient without treatment but disease free Preliminary data, status 06th November, 2017 25

  26. Slide 26: Thank you

    Thank you Frédéric Triebel MD, PhD Keynote session: immuno-oncology and strategies to improve patient success WATRMC, London. May 17, 2018

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