Immutep Ltd · ASX:IMM
Immutep — Investor Presentation (September 2019)
39 slides from Immutep's investor presentation, Sep 30, 2019
Slide 1: The global leader in developing LAG-3 therapeutics
For personal use only The global leader in developing LAG-3 therapeutics Investor Presentation 2019 (ASX: IMM, NASDAQ: IMMP)
Slide 2: Notice: Forward Looking Statements
Notice: Forward Looking Statements For personal use only 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
Slide 3: Investment Highlights
Investment Highlights For personal use only Global Leader in • More clinical-stage LAG-3 programs than any other company Development of LAG-3 • Dr. Frédéric Triebel, MD Ph.D., Chief Scientific Officer and Chief Medical Therapeutics Officer, discovered the LAG-3 gene in 1990 Best-and-First-in-Class/
Slide 4: Company Snapshot
Company Snapshot For personal use only Financial Snapshot • Globally active biotechnology company with IMM (Australian Securities Exchange) Ticker symbols IMMP (NASDAQ) operations in Australia, Europe and U.S. 3.87 billion ordinary shares Securities on issue(1) 10.9 million American Depository (as a
Slide 5: LAG-3 Overview & Product Candidates
For personal use only LAG-3 Overview & Product Candidates
Slide 6: LAG-3 as a Therapeutic Target
LAG-3 as a Therapeutic Target For personal use only LAG-3 is widely expressed on tumor infiltrating lymphocytes (TILs) and cytotoxic T cells → Prime target for an immune checkpoint blocker LAG-3/ MHC Class II Interaction → Positive regulation of antigen presenting cells LAG-3 (APC) → increase in ant
Slide 7: 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 For personal use only IMMUNOSTIMULATION IMMUNOSUPPRESSION Efti APC Activator APC Agonistic mAb IMP761 MHCII Depleting mAb LAG-3 Antagonistic Partnered with mAb Partnered with LAG-3 LAG525 T Cell T Cell GSK’781 Rheumatoi
Slide 8: Immutep Controlled Immunotherapy Pipeline
Immutep Controlled Immunotherapy Pipeline* For personal use only Commercial Program Preclinical Phase I Phase II Late Stage(5) Rights AIPAC (Chemo-IO Combo) Metastatic Breast Cancer 2019 TACTI-002 (1) (IO-IO Combo) NSCLC (1st/2nd L.) HNSCC (2nd) 2019 Eftilagimod Alpha Global Rights INSIGHT-004 (2),
Slide 9: Out-Licensed Immunotherapy Pipeline
Out-Licensed Immunotherapy Pipeline* For personal use only Commercial Program Preclinical Phase I Phase II Late Stage(1) Rights/Partners IO-IO Combo: Solid Tumors + Blood Cancer Chemo-IO Combo: Triple Negative Breast Cancer Oncology LAG525 Global Rights IO-IO-Small Molecule Combo: Melanoma (Antagoni
Slide 10: Lead Program Eftilagimod Alpha (IMP321)
For personal use only Lead Program Eftilagimod Alpha (IMP321)
Slide 11: Efti Mechanism of Action (MOA)
Efti Mechanism of Action (MOA) Efti’s unique agonistic MOA leads to T cell expansion and proliferation => For personal use only pushing the gas on the immune response Efti binds to MHC class II on monocytes DC/ monocyte activation induced Leads to T cell expansion and proliferation 11
Slide 12: Opportunity for Eftilagimod Alpha
Opportunity for Eftilagimod Alpha For personal use only Efti has multiple shots on goal in different indications and in different combinations • Best-and-First-In-Class MHCII agonist • Good safety profile and encouraging efficacy data thus far • Estimated favorable (low) cost of goods, current flat
Slide 13: Efti - Clinical Development AIPAC
Efti - Clinical Development AIPAC For personal use only AIPAC: Active Immunotherapy PAClitaxel in HER2-/ HR+ MBC Arm 1, 113 patients: Phase IIb, Safety-run in, paclitaxel + IMP321 multinational, Run-in: RP2D 15 (6+9) patients, Stage 2 randomized, Stage 2: Efficacy (PFS) 2 cohorts Arm 2, 113 patients
Slide 14: Eftilagimod Alpha Preliminary Efficacy
Eftilagimod Alpha Preliminary Efficacy Metastatic Breast Cancer For personal use only Observed response rates are substantially better than the 22-33% response rates seen in historical control groups with paclitaxel monotherapy Phase I (n=30) AIPAC – Safety Run Phase (n=15) Response Parameter Paclit
Slide 15: Efti Pharmacodynamic Effect: Primary Target Cells
Efti Pharmacodynamic Effect AIPAC Immunomonitoring: Primary Target Cells For personal use only Primary target cells: Sustained increase of circulating Antigen- Presenting Cells (APCs) like monocytes (A) and dendritic cells (B). Rapid activation of monocytes (CD16 (C) and CD40 (D)). 15
Slide 16: Efti Pharmacodynamic Effect: Secondary Target Cells
Efti Pharmacodynamic Effect AIPAC Immunomonitoring: Secondary Target Cells For personal use only Secondary target cells: Sustainable increase in absolute numbers of effector cells like i.e. CD8 T cells (A) and Natural Killer cells (B). IMP321 induces early and sustainable increase of Th1 biomarkers
Slide 17: Efti in Melanoma: TACTI-mel Trial Design
Efti in Melanoma TACTI-mel – Trial Design For personal use only 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 Status
Slide 18: TACTI-mel – Results Part A
Efti in Melanoma TACTI-mel – Results Part A For personal use only Majority not responding to pembrolizumab monotherapy → Tumor shrinkage in 56 % incl. 2 pts with disappearance of all target lesions Best Overall Response N = 18 (%) Spider plot* (part A) Waterfall plot* (part A) acc. to irRC (starting
Slide 19: TACTI-mel – Results Part A – Single Case
Efti in Melanoma TACTI-mel – Results Part A – Single Case For personal use only Efficacy: Metastatic Melanoma Tumor progression • Patient progressing on pembrolizumab monotherapy • At 1 yr all lesions disappeared → CR (confirmed) • Patient without treatment and disease free → now lost to FU Prelimin
Slide 20: TACTI-mel – Results Part B
Efti in Melanoma TACTI-mel – Results Part B For personal use only Confirmed deep partial responses in 3 (50%) of the pts Treatment of 4 pts ongoing, all over 9 months Baseline Characteristics N = 6 (%) Spider plot* (part B) Waterfall plot* (part B) Best response: ECOG (0/1) 3 (50 %) / 3 (50 %) 125 1
Slide 21: Efti - Clinical Development TACTI-002 (Phase II)
Efti - Clinical Development TACTI-002 (Phase II) For personal use only TACTI-002: Two ACTive Immunotherapeutics in different indications Simon’s 2 stage Efti (IMP321) + Pembrolizumab Phase II, multi- ORR, PFS, OS, PK, design; 3 indications; (Keytruda) for 12 months + 12 national (EU + US Biomarker;
Slide 22: Efti - Clinical Development INSIGHT-004 (Phase I)
Efti - Clinical Development INSIGHT-004 (Phase I) For personal use only INSIGHT-004 – Dose escalation of efti in combination with avelumab Dose escalation, Efti (IMP321) + Avelumab Phase I, solid tumors, 2 (Bavenico) for 6 months + 6 monocenter DE, RP2D, Safety, ORR, cohorts of 6 pts each months av
Slide 23: Eftilagimod Alpha Partnerships
Eftilagimod Alpha Partnerships • Eddingpharm holds Chinese rights For personal use only • EOC, an Eddingpharm spin-off holding the Chinese rights for efti, Phase I study in MBC ongoing • Milestone and royalty bearing partnership for Immutep where EOC bears all the costs of funding the trials -> Immu
Slide 24: IMP761 (Autoimmune Diseases)
For personal use only IMP761 (Autoimmune Diseases)
Slide 25: Broad Potential in Targeting Auto-reactive Memory T cells with IMP761
Broad Potential in Targeting Auto-reactive Memory T cells with IMP61 For personal use only THE PRESENT: FIGHTING SYMPTOMS Treating general inflammation: corticoids, methotrexate, anti-TNF-α, -IL-6, -IL-17, -IL-23 mAbs THE FUTURE: FIGHTING THE CAUSE OF AID Treating the disease process: silencing the
Slide 26: IMP761 – Agonist mAb
IMP761 – Agonist mAb For personal use only IMP761 Key Characteristics • Humanized IgG4 monoclonal antibody LAG-3 • LAG-3 agonist mAb T Cell • Mechanism of action: temporarily switches off LAG-3 positive chronically activated T-Cells Development Activities ✓ In vitro/ in vivo studies completed (cynom
Slide 27: IMP761 Intervenes Upstream from Current Therapeutics
IMP761 Intervenes Upstream from Current Therapeutics For personal use only Auto-immune memory T cells are chronically stimulated by the same self-peptide, acquiring an ‘exhausted’ phenotype and expressing LAG-3 which down-modulates specifically TCR signaling. IMP761 increases this physiological down
Slide 28: Delayed-Type Hypersensitivity Model in Cynomolgus Monkey
Delayed-Type Hypersensitivity Model in Cynomolgus Monkey For personal use only Study design Immunofluorescence staining: IMP761/PBS inflammatory T cell infiltration at BCG1 BCG2 Tuberculin test 1 Tuberculin test 2 tuberculin test site before and after IMP761/PBS injection D-45 D-30 D-15/-13 D0 D1/3
Slide 29: IMP761 Inhibits Inflammatory T Cell Infiltration in vivo
IMP761 Inhibits Inflammatory T Cell Infiltration in vivo For personal use only IMP761 is able to inhibit significantly T cell infiltration of an antigen-specific intradermal reaction PBS / IMP761 TB test 1 TB test 2 % CD3+ cells infiltration Inflammatory C D 3 in f ilt r aTt io celln infiltration te
Slide 30: Conclusion
Conclusion For personal use only • The Concept: treating the cause of autoimmune diseases, not just the symptoms • The Target: the self-peptide specific memory T cells harboring LAG-3 • The Tool: an agonistic LAG-3-specific mAb down-modulating self-peptide-induced TCR signaling • The Evidence (1): i
Slide 31: Partnered Programs
For personal use only Partnered Programs
Slide 32: GSK'781 (IMP731) for Autoimmune Diseases
GSK’781 (IMP731) for Autoimmune Diseases • GSK holds exclusive WW rights For personal use only • Up to ₤64m in total upfront payments and milestones, plus royalties • Sept 2019: 1st patient dosed in phase 2 trial triggered a £4m (~A$7.4 million or ~US$ 5.0 million) milestone payment to Immutep • Por
Slide 33: LAG525 (IMP701) for Cancer
LAG525 (IMP701) for Cancer(1) • Novartis holds exclusive WW rights For personal use only • In 2015: Started Phase I study of LAG525 (derived from IMP701) in combination with PDR001 (anti-PD-1 mAb) in different cancer indications in 490 patients • 1st and 2nd Milestone payments received in Aug 2015 (
Slide 34: LAG-3 Landscape
For personal use only LAG-3 Landscape
Slide 35: LAG-3 Therapeutic Landscape Overview
LAG-3 Therapeutic Landscape Overview For personal use only Company Program Preclinical Phase I Phase II Phase III Total Trials Patients on Trials Agonist Eftilagimod Alpha Eftilagimod Alpha 2 3 22 4244 424 BMS Relatlimab 6 19 2 27 9,422 Novartis LAG525 (IMP701) 1 4 1,122 LAG525 (IMP701) 1 4 5 1,100
Slide 36: IP & Outlook
For personal use only IP & Outlook
Slide 37: Intellectual Property
Intellectual Property For personal use only Immutep has a strong and continually expanding patent portfolio across major geographic markets and unrivalled expertise and understanding of the LAG-3 immune control mechanism #Plus up to a 5 year extension of term available in some circumstances to compe
Slide 38: 2019/2020 Clinical Guidance
2019/ 2020 Clinical Guidance* ✓ TACTI-002 to commence, Phase II trial in collaboration with MSD: H1 2019 For personal use only ✓ TACTI-mel data from fourth patient cohort (30 mg dose at cycle 1) in 2019 ✓ IMP761 program update: 2019 ✓ INSIGHT-004 to commence, IIT Phase I trial in collaboration with
Slide 39: Investment Highlights
Investment Highlights For personal use only Global Leader in • More clinical-stage LAG-3 programs than any other company Development of LAG-3 • Dr. Frédéric Triebel, MD Ph.D., Chief Scientific Officer and Chief Medical Therapeutics Officer, discovered the LAG-3 gene in 1990 Best-and-First-in-Class/