Immutep Ltd · ASX:IMM

Immutep — Non-Small Cell Cancer Drug Development Summit (July 2021)

23 slides from Immutep's conference presentation, Jul 15, 2021

  1. Slide 1: A soluble LAG-3 protein (eftilagimod alpha) with an anti-PD-1 antibody: results of a phase II study 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 Virtual meeting, July 15th 2021

  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: MHC II / LAG-3 Interaction as a Therapeutic Target

    MHC II / LAG-3 Interaction as a Therapeutic Target 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 antigen presenting cells (APCs)  Prime target for immune therapy LAG-3 / MHC Class II Inte

  4. Slide 4: What is LAG-3?

    : i=J immutep What is LAG-3?

  5. Slide 5: 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 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

  6. Slide 6: Immunological mechanisms elicited at the tumour site by LAG-3 versus IL-12

    Immunological mechanisms elicited at the tumour site by LAG-3 versus IL-12: sharing a common Th1 anti-tumour immune pathway The mammary adenocarcinoma TS/A tumor is rejected in mice when TS/A cells express hLAG-3, mLAG-3 or mIL-12 (positive control). TS/A-pc: untransfected parental cells (negative c

  7. Slide 7: Immunological mechanisms elicited at the tumour site by LAG-3 versus IL-12

    Immunological mechanisms elicited at the tumour site by LAG-3 versus IL-12: sharing a common Th1 anti-tumour immune pathway The mammary adenocarcinoma TS/A tumor is rejected in mice when TS/A cells express hLAG-3, mLAG-3 or mIL-12. TS/A-pc: untransfected parental cells. 7

  8. Slide 8: Eftilagimod Alpha (efti or IMP321)

    Eftilagimod Alpha (efti or IMP321)

  9. Slide 9: 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 D2 “LAG-3

  10. 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 monocytes DC / monocyte activation induced Leads to T cell expansion and proliferation Notes: https://www.youtu

  11. Slide 11: The synergistic benefit of APC activation in combination with ICI

    The synergistic benefit of APC activation in combination with ICI “Pushing the gas pedal” • Efti induces sustained APC activation  boost the effector memory CD8 compartment to a more tumor- aggressive TH1-driven phenotype “Releasing the brakes” • The efti induced sustained increase of activated CD8

  12. Slide 12: Efti: an Innovative LAG-3 I-O Product Candidate

    Efti: an Innovative LAG-3 I-O Product Candidate • Efti is a soluble LAG-3 protein targeting a subset of MHC class II on APC • Potentially synergistic with other therapeutic agents e.g. immuno-oncology (I-O) agents & chemotherapies “PUSHING THE ACCELERATOR ON IMMUNE RESPONSES” “RELEASING THE BRAKE ON

  13. Slide 13: Efti as an MHC class II agonist

    Efti as an MHC class II agonist 100 In vitro bioactivity of efti (IMP321). IMP321 potency to induce CCL4 (MIP-1) secretion was tested using the MHC class II+ human monocytic THP-1 cells. The results are presented as concentration of CCL4 produced in supernatant after 4hrs of culture (mean of 5-plic

  14. Slide 14: Efti: Potential Pipeline in a Product

    Efti: Potential Pipeline in a Product Potential for use in various combination settings Unique MHC II agonist Excellent safety profile Encouraging efficacy data Low cost of goods Unique protective IP positioning (unlike ICI mAbs) Chemo-IO combo IO-IO combo 14

  15. Slide 15: Efti + anti-PD-1 Combination TACTI-002

    Efti + anti-PD-1 Combination TACTI-002 “Two ACTive Immunotherapies”

  16. Slide 16: TACTI-002 (Phase II) Design & Status

    TACTI-002 (Phase II) Design & Status TACTI-002: Two ACTive Immunotherapeutics in NSCLC and HNSCC UNSELECTED FOR PD-L1 In collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & PART A: Co., Inc., Kenilworth, NJ, USA S 1ST LINE MET. NSCLC C R PART B: COMBINED E ORR, PFS, OS, PK, 2ND LIN

  17. Slide 17: TACTI-002 (Phase II) Safety

    TACTI-002 (Phase II) Safety Efti + Pembro combination has a favourable safety profile Summary TACTI-002 Selected safety aspects of other treatment regimens (N=115 in total) • No (0%) treatment-related death Treatment related Treatment related Regimen(2) adverse events leading adverse events • 4 (3.5

  18. Slide 18: TACTI-002 Results: 1st line NSCLC (Part A)

    TACTI-002 Results(1) 1st line NSCLC (Part A) • PD-L1 distribution as expected (~70% with < 50% PD-L1 expression)  PD-L1 all comer trial • Patients are typical NSCLC 1st line pts Local Read Blinded Read Baseline parameters N (%) Best overall response, iRECIST, N = 36 (investigator) (BICR) N (%) N (%

  19. Slide 19: TACTI-002 Results: 1st line NSCLC (Part A)

    TACTI-002 Results(1) 1st line NSCLC (Part A) % change compared to baseline PD-L1 TPS … patients still under therapy Duration of response (DoR) • Responses at all PD-L1 levels including 1 • 92% responses confirmed Complete Response with TPS of 0% • 58% confirmed responses ongoing with 6+ months • At

  20. Slide 20: Conclusion

    TACTI-002: Phase II of efti and pembrolizumab in 1st line metastatic NSCLC (Part A) CONCLUSION SAFETY EFFICACY • Treatment with efti plus pembrolizumab is well- • Encouraging ORR (41.7 % by BICR) in patients tolerated with no new safety signals unselected for PD-L1 • 4 % of patients discontinued tre

  21. Slide 21: TACTI-002 (Phase II) Part B: a difficult to treat population

    TACTI-002 (Phase II) Part B: a difficult to treat population TACTI-002: Two ACTive Immunotherapeutics in NSCLC and HNSCC UNSELECTED FOR PD-L1 In collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & PART A: Co., Inc., Kenilworth, NJ, USA S 1ST LINE MET. NSCLC C R PART B: COMBINED E O

  22. Slide 22: TACTI-002 Results: 2nd line NSCLC PD-X refractory/resistant (Part B)

    TACTI-002 Results1 – 2nd line NSCLC PD-X refractory/resistant (Part B) Enrolment to stage 1 completed Q3 2020 Baseline Stage 1 (N=23) Stage 1 (N=23) Characteristics N (%) Tumor response (RECIST 1.1) N (%) Median age, years 67.0 (46-84) Partial Response 1 (4.4) (range) Female 10 (43.5) Stable Disease

  23. Slide 23: Thank You

    Thank You Frédéric Triebel MD, PhD Non-Small Cell Cancer Drug Development Summit Virtual meeting, July 15th, 2021

Immutep — Non-Small Cell Cancer Drug Development Summit (July 2021) on 6ix