Abstract #: 6028 Results From A Phase II Study Of .

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Abstract #: 6028Results from a Phase II study of eftilagimod alpha(soluble LAG-3 protein) and pembrolizumab in patientswith PD-L1 unselected metastatic 2nd line squamoushead and neck carcinomaPresenting Author: Dr. Irene BrañaAuthors: I Braña1, M Forster2, A Lopez Pousa 3, B Doger4, P Roxburgh5, P Bajaj6, D Urueta7,V Quiroga8, M Krebs9, C Muelller10, F Triebel11Affiliates: 1Vall d‘Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; 2 UCL CancerInstitute / University College London Hospitals NHS Foundation, London, UK; 3 Hospital de la Santa Creu i Sant Pau, Barcelona,Spain; 4 START Madrid- Fundación Jiménez Diaz, Madrid, Spain; 5Institute of Cancer Sciences, University of Glasgow and TheBeatson West of Scotland Cancer Centre, Glasgow, UK; 6 Tasman Oncology, Queensland, Australia; 7 Oncology Consultants, P.A.,Houston, USA; 8 Catalan Institute of Oncology Badalona-Hospital Germans Trias i Pujol, B-ARGO group; Badalona, Spain; 9Division of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK; 10 ClinicalDevelopment, Immutep GmbH, Berlin, Germany; 11 Research & Development, Immutep S.A.S., Orsay, FranceStudy Identifiers:Sponsor: IMP321-P015; MSD: Keynote-PN798; EudraCT: 2018-001994-25; Clinicaltrials.gov: NCT03625323Corresponding author: Frederic Triebel, frederic.triebel@immutep.com

DISCLOSUREAbstract #: 6028I Braña: Consulting or Advisory Role- Merck Sharp & Dohme, Rakuten Medical, Sanofi, AchillesTherapeutics, eTheRNA Immunotherapies, Cancer Expert Now. Speakers Bureau: Bristol-Myers Squibb,Merck Serono, Roche. Research Funding: AstraZeneca, Bristol-Myers Squibb, Celgene, Gliknik,GlaxoSmithKline, Janssen Oncology, Kura, Merck Sharp & Dohme, Novartis, Orion Pharma GmbH, Pfizer,Roche, Shattuck Labs, Nanobiotix, Seattle Genetics, Immutep. Travel, Accommodations, Expenses AstraZeneca Spain, Merck Serono.2

Eftilagimod alpha (efti) MoAMoA: Efti is a soluble LAG-3 protein targetinga subset of MHC class II molecules to mediateantigen presenting cells (APCs) and CD8 T-cellactivation.Rationale: Efti activates APCs, leading to an increasein activated T cells, thus potentially reducing thenumber of non-responders to PD-1/PD-L1antagonists (e.g. pembrolizumab).TACTI-002TRIAL DESIGN & INTRODUCTION Phase II, multinational, open label, PD-L1 all-comer, multiple indications Up to 183 pts in a Simon's optimal two-stage design (NCT03625323) Sponsored by Immutep and in collaboration with MSD“PUSHING THE ACCELERATOR ON IMMUNE RESPONSES” Following patients are eligible to part C (2nd line HNSCC):patients unselected for PD-L1 with recurrent HNSCC disease unamenable tocurative treatment with local or systemic therapy, or metastatic(disseminated) disease incurable by local therapies, who progressed on orafter 1st line platinum-based therapy 39 patients were enrolled to stage 1 2 (LPI in Jan 2021) Primary objective: Overall Response Rate acc. to iRECIST Secondary objectives include PFS, OS, PK, biomarker, PD, safety and tolerability Data cut-off: 16th April 2021 (interim data)3APC antigen-presenting celliRECIST Immune Response Evaluation Criteria In Solid TumorsLAG-3. Lymphocyte Activation gene-3MHC Major Histocompatibility ComplexMoA Mode of ActionPD-L1, PD-L2.Programmed Death ligand-1, -2PFS progression-free survivalAbstract #: 6028

TACTI-002: Phase II of efti and pembrolizumab in 2nd line HNSCC (Part C)SAFETY*Table 1: Treatment-emergent adverse events occurring 10%*Any gradeN (%)Grade 3N (%)Grade 4/5N (%)Hypothyroidism8 (20.5)1 (2.6)-Cough7 (17.9)--Asthenia6 (15.4)--Fatigue5 (12.8)--Anaemia5 (12.8)4 (10.3)Diarrhoea5 (12.8)--Weight decreased5 (12.8)--URTI4 (10.3)--Back pain4 (10.3)--Pain in extremity4 (10.3)2 (5.1)-Adverse event (PT)Table 2: General overview of adverse events*Safety parameterN (%)Patients with any TEAE35 (89.7)Patients with any SAE18 (46.2)thereof related to efti/pembro2 (5.1) / 2 (5.1)Patients with any grade 3 TEAE24 (61.5)thereof related to efti/pembroPatients with fatal TEAEsthereof related to efti/pembroPatients with TEAEs leading todiscontinuation of any study treatmentthereof related to efti/pembro4 (10.3) / 3 (7.7)7 (17.9)0/07 (17.9)1 (2.6)* - Safety is displayed for all patients (N 39) recruited who received 1 treatment4SAE serious adverse eventTEAE treatment-emergent adverse eventAbstract #: 6028

TACTI-002: Phase II of efti and pembrolizumab in 2nd line HNSCC (Part C)BASELINE CHARACTERISTICS & EFFICACY*Table 3: Baseline disease characteristicsBaseline parameters(N 39)N (%)Age, median (years)62 (37-84)Female /Male4 (10.3) /35 (89.7)ECOG 0 /ECOG 113 (33.3) /26 (66.7)Current /Ex- or Non-smokers6 (15.4) /33 (84.6)Previous chemotherapy39 (100)Previous cetuximabLung lesionsLiver lesions516 (41.0)19 (48.7) /6 (17.6)ECOG Eastern Cooperative Oncology GroupiRECIST Immune Response Evaluation Criteria In Solid TumorsTable 4: Primary tumor locationPrimary tumourlocation (N 39)N (%)Table 5: Tumor response*Best overall response*, iRECISTInvestigatorassessment N (%)Oral cavity12 (30.8)Complete Response5 (13.5)Oropharynx14 (35.9)Partial Response6 (16.2)Hypopharynx7 (17.9)Stable Disease3 (8.1)Larynx6 (15.4)Progression17 (45.9)Not evaluable**6 (16.2)Disease Control Rate14 (37.8)Overall Response Rate[95 % CI interval]11 (29.7)[15.9 – 47.0]Overall Response Rate – Evaluable pts***[95 % CI interval]11 (35.5)[19.2 – 54.6]* - All patients (N 37) with 1 treatment and no death due to COVID-19 prior to firstpost-baseline staging** - dropped off prior to first staging or were not evaluable post-baseline for any reason*** - evaluable patients (N 31): 1 treatment and 1 post baseline tumor stagingAbstract #: 6028

TACTI-002: Phase II of efti and pembrolizumab in 2nd line HNSCC (Part C)EFFICACY*75 Deep responses with5 CRs50Best response:iUPD/iCPDiSDiPRiCRProbability of Survival100Figure 2: Kaplan-Meier Plot PFS*25PD-L1 CPS0-25Overall: Median PFS 2.1mts 30 %progressionfree at 6 mts-50-75-100n 31Figure 4: Spider plot*** - NE - not evaluable; NY - not yet evaluated ** LN as target lesion; *** targetlesion decrease at PD due to NL 9 pts still undertherapyTable 6. ORR, PFS, DoR, OS for pts with CPS 1 (N 24)*OS(58 % events)PFS(71 % events)ORR iRECIST(95 % CI) Median 12.6 mts 54 % alive at 12mts Median 4.1 mts 45 % PFS freeat 6 mts45.8 %(25.6-67.2)Figure 3: Duration of response(DOR) for confirmed respondersProbability of SurvivalFigure 1: Waterfall plot**Duration of response 91 % confirmed responses 80 % confirmed responsesongoing (censoring at 4-20months Figure 3) No progression prior to 6months DOR Median duration of responsecannot be estimated yet* 1 treatment and no death due to COVID-19 prior to first post-baseline staging (N 37)** 1 post baseline tumor staging (N 31)6iRECIST Immune Response Evaluation Criteria In Solid TumorsPD-L1, PD-L2.Programmed Death ligand-1, -2PFS progression-free survivalORR objective response rateNL new lesionDOR Duration of Response . patients still under therapyAbstract #: 6028

TACTI-002: Phase II of efti and pembrolizumab in 2nd line HNSCC (Part C)CONCLUSIONSAFETY Treatment with efti plus pembrolizumab is welltolerated with no new safety signals Majority of most frequent adverse events are mildto moderate Safety profile compares well to KN-040(pembrolizumab monotherapy)EFFICACY Encouraging ORR (30 % acc. to iRECIST) in patientsunselected for PD-L1 13.5 % complete responses observed Responses were durable with median DOR not yetreached In pts with PD-L1 CPS 1, ORR was 45.8 % (95 % CI25.6-67.2), median PFS of 4.1 months and medianOS of 12.6 months Efficacy in PD-L1 CPS 1 encouraging compared toKN-040 (PIII, randomized trial)The combination of efti plus pembrolizumab is well-tolerated and showsencouraging signs of activity supporting further clinical investigation. Astudy in 1st line HNSCC patients has been initiated (NCT04811027).7AE adverse eventPD-L1, PD-L2.Programmed Death ligand-1, -2PFS progression-free survivalORR objective response rateAbstract #: 6028

Median 4.1 mts 45 % PFS free at 6 mts 45.8 % (25.6-67.2) Figure 1: Waterfallplot** Figure 4: Spider plot** Figure 3: Duration of response (DOR) for confirmed responders Probability of Survival Probability of Survival Figure 2: Kaplan-Meier Plot PFS* Overall: Median PFS 2.1 mts 30 % progression free at 6 mts Deep responses with 5 CRs

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