Full Press Release Details
& Time: 8.00 am AEDT (Sydney) Wednesday 17 November 2021 4.00 pm EST (New York) Tuesday 16 November 2021 10.00 pm CET (Berlin) Tuesday 16 November 2021 Register: https://fnn.webex.com/fnn/onstage/g.php?MTID=ef12af93633b5d17a2e4e176fcac2f070 A
replay of the webcast will also be available at www.immutep.com (ASX: IMM, NASDAQ: IMMP)
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 clarification.
Accordingly, these slides and the information they contain should be read in conjunction with past and future announcements made by Immutep and should not be relied upon as an independent source of information. Please refer to the Company's website
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warranty is made as to the accuracy, completeness or reliability of the information. Any forward looking statements in this presentation have been prepared on the basis of a number of assumptions which may prove incorrect and the current intentions,
plans, expectations and beliefs about future events are subject to risks, uncertainties and other factors, many of which are outside Immutep's control. Important factors that could cause actual results to differ materially from assumptions or
expectations expressed or implied in this presentation include known and unknown risks. Because actual results could differ materially to assumptions made and Immutep's current intentions, plans, expectations and beliefs about the future, you
are urged to view all forward looking statements contained in this presentation with caution. This presentation should not be relied on as a recommendation or forecast by Immutep. Nothing in this presentation should be construed as either an offer
to sell or a solicitation of an offer to buy or sell shares in any jurisdiction. This presentation is authorised for release by the CEO of Immutep Limited. 2
Overview Immutep Collaborating with industry is an innovative
biotechnology leaders company developing novel immunotherapies for cancer and autoimmune disease Globally active Leadership position in LAG-3 with 4 product candidates in immuno-oncology and autoimmune disease Clinical Potential LAG-3 Pioneer
Immutep's product candidates have French immunologist demonstrated clinical potential in a Prof. Fr d ric Triebel, Immutep range of indications with high unmet CMO & CSO need 3
LAG-3 Overview & Product Candidates 4
LAG-3 Therapeutic Landscape Overview Company Program Preclinical Phase I
Phase II Phase III Total Trials Patients Eftilagimod 10 4 14 967 (5) Alpha (6) 7 32 2 BMS Relatlimab 41 9,775 Merck & Co. Inc. Favezelimab 1 5 6 1066 PDUFA goal date March 19, 2022 Ieramilimab 1 4 5 952 Macrogenics Tebotelimab 3 3 6 1422 1 2 H-L
Roche RO7247669 3 538 4 1 B.I. BI754111 5 649 (1) Regeneron Fianlimab 1 1 2 836 Innovent IBI110 1 1 2 328 (3) Tesaro TSR-033 1 1 2 139 1 Incyte INCAGN02385 1 2 74 (2) 3 Symphogen SYM022 3 169 F-star FS-118 2 2 102 1 Xencor XmAb-22841 1 242 IMP761 --
-- (4) GSK2831781 2 3 207 1 (IMP731) Sources: GlobalData, Company websites, clinicaltrials.gov, and sec.gov, as of 25th October 2021. The green bars above represent programs conducted by Immutep &/or its partners. Total trials includes all
active, completed &/or inactive trials. Patient totals are based on estimated total enrolled &/or to be enrolled. Not a complete list of currently existing LAG-3 products. 1) As of January 7, 2019 Regeneron is in full control of program and
continuing development 4) Includes two completed Phase I studies and one discontinued Phase 2 study (https://www.sec.gov/Archives/edgar/data/872589/000110465919000977/a19-1325_18k.htm) 5) Including IITs, one planned trials (MBC trial by EOC) 2) On 3
Apr. 2020 Les Laboratoires Servier acquired Symphogen 6) RELATIVITY-047 (https://investors.bms.com/iframes/press-releases/press-release-details/2021/Bristol-Myers-Squibb-Announces-RELATIVITY- 5
047-a-Trial-Evaluating-Anti-LAG-3-Antibody-Relatlimab-and-Opdivo-nivolumab-in-Patients-with-Previously-Untreated-Metastatic-or-Unresectable- 3) Tesaro was acquired by and is now part of GSK
(www.gsk.com/en-gb/media/press-releases/gsk-completes-acquisition-of- Melanoma-Meets-Primary-Endpoint-of-Progression-Free-Survival/default.aspx) tesaro-an-oncology-focused-biopharmaceutical-company/ ) Autoimmune Oncology Depleting Agonist Antagonist
Eftilagimod Alpha Bringing APC Activation into Oncology Eftilagimod
alpha ~ Efti ~ IMP321 6
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 or chemotherapies "PUSHING THE ACCELERATOR ON IMMUNE RESPONSES"
"RELEASING THE BRAKE ON THE T CELL" Efti is an MHC II agonist: LAG-3 antagonist, or blocking, antibodies: APC activator Immune checkpoint inhibitor + boost and sustain the CD8 T cell responses increase cytotoxicity of the
pre-existing CD8 activate multiple immune cell subsets T cell response Notes: 7 * APC: antigen presenting cell
Clinical Development Efti: Main Trials* Commercial (5) Program
Preclinical Phase I Phase II Late Stage Rights (1) Metastatic Breast Cancer (Chemo - IO) AIPAC-003 Metastatic Breast Cancer (Chemo - IO) AIPAC (2) Head and Neck Squamous Cell Carcinoma (IO - IO) TACTI-003 (2) Head and Neck Squamous
Cell Carcinoma (IO - IO) TACTI-002 (2) Non-Small-Cell Lung Carcinoma (IO - IO) Eftilagimod Alpha TACTI-002 (Efti or IMP321) Global Rights (3) Solid Tumors (IO - IO - Chemo) APC activating INSIGHT-003 soluble LAG-3 (3),
(4a) Solid Tumors (IO - IO) Protein INSIGHT-004 (1), (3), (4b) Solid Tumors (IO - IO) INSIGHT-005 (2) Melanoma (IO - IO) TACTI-mel (5a) Solid Tumors (Cancer Vaccine) YNP01 / YCP02 / CRESCENT 1 Chinese Rights (5b) Metastatic Breast
Cancer (Chemo - IO) Notes: * Information in pipeline chart current as at November 2021. AIPAC-003 and INSIGHT-005 trial initiation are subject to further approvals. (4) a) In combination with BAVENCIO (avelumab); b) in combination
with Bintrafusp alfa (1) Planned trial (5) a) Conducted by CYTLIMIC in Japan; b) Conducted by EOC in China. Immutep has no control over either of these trials. 8 (2) In combination with KEYTRUDA (pembrolizumab) (6) Late stage refers to Phase
IIb clinical trials or more clinically advanced clinical trials (3) INSIGHT Investigator Initiated Trial ("IIT") is controlled by lead investigator and therefore Immutep has no control over this clinical trial Oncology
Clinical Development Operational Update TACTI-002 Recruitment
into Part A (1st line NSCLC) is expected to be completed ahead of time, due to great interest from sites. 70+ of 74 patients for part A extension already enrolled. TACTI-003 Full CTA approvals received in 5 of 8 countries
no roadblocks or any major comments received from authorities. Recruitment initiated, first patients randomized. INSIGHT INSIGHT-003 (efti+SoC (e.g. doublet chemo + PD-1) in e.g. 1st line NSCLC) has enrolled already 5 patients.
Preparation for INSIGHT-005 collaboration with Merck KGaA are ongoing, but under review due to bintrafusp alfa performance. AIPAC-003 Positive feedback from EMA received. FDA discussion ongoing as planned. 9
Efti + Chemo Combination AIPAC trial Final OS results presented at
SITC, 10-14 November 2021 10
Goal: Improving OS while maintaining QoL in + - HR /HER2 MBC
patients Epidemiology: Breast cancer (BC) is the most frequently diagnosed cancer. More than 2 million breast cancer (thereof ~70% + -- HR /HER2 ) diagnoses per annum worldwide. Up to 550,000 patients in total and app. 350,000
patients younger than 65 develop metastatic disease and are (1) (2) eligible to receive chemotherapy ~10% ~35% Lack of Innovation Weekly paclitaxel well ~55% established SOC Notes (1) Source: WHO Global Cancer Observatory 2020 and Informa
Intelligence October 2020 11 (2) Wang et al. BMC Cancer (2019) 19:1091 MBC - metastatic breast cancer; BC - Breast Cancer
Efti: AIPAC (Phase IIb) design - + AIPAC: Active Immunotherapy
PAClitaxel in HER2 / HR metastatic breast cancer (MBC) Fact sheet Hypothesis-Generating Study ( ) Conducted in 7 EU countries Primary endpoint * (presented Mar. 2020) included: Local and blinded independent central read
Assessment of Progression-Free Survival (PFS) ( ) Last Patient In enrolled Jun. 2019 Secondary endpoints * (presented Dec. 2020) included: Overall Survival (OS) Primary analysis PFS (immature OS) Mar. 2020 Safety
and tolerability Follow-up 1 analysis OS Sep. 2020 (SABCS Overall Response Rate (ORR) and other efficacy parameters Dec. 2020) - ~60% OS events Biomarker and Immune Monitoring Final OS analysis at SITC 2021
Notes: * No hypothesis testing 12 ORR - overall response rate, DCR - disease control rate, PFS - progression free survival, OS - overall survival, QoL - Quality of life
AIPAC Phase IIb Clinical Results Baseline Characteristics Well
balanced treatment groups. Difficult to treat patient population: Very late stage disease: 92% with visceral disease and 69% with elevated LDH Heavily pre-treated subjects: 84% endocrine resistant; 44% received prior CDK
4/6; median of 2 prior systemic anticancer regimens. + - HR /HER2 tumor is traditionally not considered immunogenic. 227 patients were randomized to efti (N=114) or to placebo (N=113) between January 2017- July 2019. All
except one patient received at least 1 dose of study medication and were included in the full analysis and safety populations. Notes: Central assessment performed on available and evaluable primary or metastatic tissues (n=169). Classified
using PgR and Ki67 index 1 according to St Gallen International Expert Consensus guidelines . 13 2 Defined according to ESMO Internal Consensus Guidelines (Advanced Breast Cancer 4) . 1. Goldhirsch A, Winer EP, Coates AS, et al.
2013;24(9):2206-2223. doi:10.1093/annonc/mdt303
AIPAC Phase IIb Clinical Results Outstanding Safety Profile Most common
( 15%) TEAEs in any arm No fatal TEAE related to efti Summary of treatment-emergent Efti + Paclitaxel Placebo + Paclitaxel adverse events (TEAEs) N=114, n (%) N=112, n (%) 3 pts discontinued due to hypersenstivity
reactions 1 TEAE 113 (99.1) 112 (100) developing after efti injections and 4 pts due to paclitaxel-induced hypersensitivity, respectively 1 TEAE leading to death 2 (1.8) 3 (2.7) 1 TEAE leading to efti/placebo Most common
efti related adverse event was any kind 6 (5.3) 7 (6.3) discontinuation of local injection site reaction up to grade 3 reported in 75 (65.8%) pts in the efti arm 1 Grade 3 TEAE 78 (68.4) 73 (65.2) Notes: 14 ORR - overall response
rate, DCR - disease control rate, PFS - progression free survival, OS - overall survival, QoL - Quality of life
Overall Unselected Population* Improving OS with better QoL Global
Health Status / QoL QLQC30-B23 * Increase in OS: +2.9 months from median of 17.5 (95% CI: 12.9- Preserving QoL in the efti arm, while significant deterioration 21.9) in placebo to 20.4 (95% CI: 14.3 -25.1) in the efti group. of QoL
(QLQ-C30-B23) observed in the placebo group at 6 months. Post-study treatment similar: 86 % (efti) vs. 90 %(placebo); majority received chemotherapy 70.2% (efti) vs. 76.8% (placebo) Note: Paclitaxel treatment intensity was similar
between groups Notes: * These results were presented at SITC 2021. Database cut-off date was May 14, 2021 (73% of events) with minimum follow up of 22 months 15
AIPAC Phase IIb Clinical Results Immune Monitoring on Fresh Blood (up
to 70 patients) Significant Increase of CD8+ T Cell Count Significant Correlation: + Minimal Residual Effect: samples taken just before next treatment OS and cytotoxic CD8 T cell count Placebo Rho= -0.2; p= 0.5 30 mg efti Rho= 0.6; p= 0.007 1000 500
300 100 10 20 30 40 50 Overall survival (months) Proof of Concept Proof of Principle Increased number of cytotoxic CD8+ T cells Number of T cells increased in efti group, correlated with improved OS in the efti arm especially cytotoxic CD8+ T cells
Notes: * These results were presented at SITC 2021. Database cut-off date was May 14, 2021 16 CD8 T cell count at 6 months 6 (10 /L of blood)
Prespecified Subgroups* Exploratory Analysis Exploratory multivariate
analyses Prior CDK 4/6 treatment is an independent poor prognostic factor with a 37% increase in risk for death. Prior CDK 4/6 has a negative impact on OS in placebo group (median reduced from 20.4 to 14.9 months), but not in the
efti group (median OS 21.9 vs. 20.2 months). CDK4/6 treatment are now standard, and most patients will have received it favorable for efti. Prespecified (prior to unblinding) exploratory univariate analysis showed that
younger patients (<65 years), those with low baseline monocytes (<0.25/nL) or breast cancer subtype luminal B had significant and clinical meaningful improvement in median OS compared to placebo. In a post-hoc multivariate analysis
"no prior taxanes" were found to be an additional predictive marker Notes: * These results were presented at SITC 2021. Database cut-off date was May 14, 2021 (73% of events) with minimum follow up of 22 months 17
Prespecified Subgroup <65 years* Clinically meaningful improvement
for OS, PFS and ORR mOS mPFS ORR +7.5 months median OS (HR 0.66; p=0.017) Benefit +7.5 months +2.0 months +8% HR 0.66 (p=0.02) HR 0.77 (p=0.07) (46% vs. 38%) Effect of age on OS Prespecified subgroup showed significant (p=0.017, one-sided)
HR point estimates for different age groups. improvement in OS with a HR of 0.66 (95% CI: 0.45-0.97). ESMO scale of magnitude** = level 4/5 (would be very Age had an almost linear effect on HR for OS. supportive for
reimbursement). Notes: * These results were presented at SITC 2021. Database cut-off date was May 14, 2021 18 ** Company assessment. ESMO-MCBS used for reimbursement in Europe:
Prespecified Subgroup Low Monocytes* Clinically meaningful improvement
for all efficacy parameters +19.6 months median OS (HR 0.44; p=0.008) Efti + Paclitaxel Placebo + Paclitaxel Benefit +19.6 months mOS 32.5 months 12.9 months HR 0.44 (p=0.008) +2.3 months mPFS 7.5 months 5.2 months HR 0.40 (p=0.006) ORR 44% 32% +12%
Clinically meaningful, absolute and relative improvement for all efficacy parameters. Statistical significance for PFS and OS. ESMO scale of magnitude** = level 4/5 (would be very supportive for reimbursement). Notes: *
Database cut-off date was May 14, 2021 19 ** Company assessment. ESMO-MCBS used for reimbursement in Europe: https://www.esmo.org/guidelines/esmo-mcbs/scale-evaluation-forms-v1.0-v1.1
Prespecified Subgroup Luminal B* Overall Survival +4.2 months median OS
(HR 0.67, p=0.049) Efti + Paclitaxel Placebo + Paclitaxel Benefit +4.2 months mOS 16.8 months 12.6 months HR 0.67 (p=0.049) +1.6 months mPFS 7.2 months 5.6 months HR 0.69 (p=0.158) ORR 43% 33% +10% Clinically meaningful improvement.
Statistical significance for OS. ESMO scale of magnitude** = = level 3/5 (would be supportive for reimbursement). Notes: * Database cut-off date was May 14, 2021 20 ** Company assessment. ESMO-MCBS used for reimbursement in Europe:
Prespecified Subgroup No Prior Taxane* Overall Survival +4.8 months
median OS (HR 0.74, p=0.076) Efti + Paclitaxel Placebo + Paclitaxel Benefit +4.8 months mOS 22.3 months 17.5 months HR 0.74 (p=0.08) +0.2 months mPFS 7.4 months 7.2 months HR 0.87 (p=0.229) Clinically meaningful improvement.
Important in multivariate predictive model ESMO scale of magnitude** = = level 3/5 (would be supportive for reimbursement). Notes: * Database cut-off date was May 14, 2021 21
AIPAC-003: Phase III in MBC General Concept (subject to further
regulatory interactions) 1) Primary Endpoint: Overall Survival Preferred endpoint for Phase III and approval by regulatory agencies in such a patient population. Seems to be a better fit for active immunotherapies such as efti. 2)
Treatment Paclitaxel will be allowed to be continued beyond 6 cycles to accommodate for EU & US standards and as a lesson from AIPAC. 3) Patient Population on Target Immutep will define the patient population and statistical
read-out in a way to increase likelihood of success. 4) Statistical Design Will be robust and pre-agreed with regulatory agencies to ensure success later during MAA/BLA procedures. 22
Efti + anti-PD-1 Combination TACTI-002 trial Update from SITC, 10-14
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 ST 1 LINE MET. NSCLC C R PART B: COMBINED E ORR, PFS, OS, PK, ND IMMUNOTHERAPY 2 LINE MET. NSCLC, E biomarker, safety and PEMBROLIZUMAB + EFTI FOR 12
REFRACTORY TO PD-1/PD-L1 MONTHS + 12 MONTHS tolerability N PEMBROLIZUMAB MONO TARGETING THERAPY I N PART C: G ND 2 LINE MET. HNSCC AFTER Recruitment Status Report Sites in Europe / US / Australia PLATINUM THERAPY Fully approved in all