Armstrong, A

Awada, A

Baurain, J-F

Brunsvig, P

Galon, J

Gjerstad, VS

Gjertsen, B-T

Hermitte, F

Jebsen, N-L

Jossang, D-E

Kristeleit, RS

Loirat, D

Marabelle, A

Nicolaisen, B

Olsen, W

Rekdal, O

Saunders, A

Spicer, J

Sveinbjornsson, B

UCL Discovery

Lytix Biopharma AS  |  Gaustadalléen 21, NO-0349 Oslo, Norway |  E-mail:  post@lytixbiopharma.com  |  Phone:  +47 77 67 55 00  |  Fax: +47 77 67 55 01LTX-315, a first in class oncolytic peptide, reshapes the tumor microenvironment in the patients with advanced metastatic tumors: Results from an ongoing studyAURELIEN MARABELLE1, JEAN-FRANCOIS BAURAIN2, AHMAD AWADA3, PAAL F. BRUNSVIG4, REBECCA SOPHIE KRISTELEIT5, DAG ERIK JØSSANG6, NINA LOUISE JEBSEN7, DELPHINE LOIRAT8, ANNE ARMSTRONG9, JEROME GALON9, FABIENNE HERMITTE10, ANDREW SAUNDERS11, ØYSTEIN REKDAL11, BALDUR SVEINBJØRNSSON11, BERIT NICOLAISEN11, VIBEKE SUNDVOLD GJERSTAD11, JAMES SPICER121INSTITUT GUSTAVE ROUSSY, PARIS, FRANCE, 2CLINIQUES UNIVERSITAIRES ST-LUC, UCL, ST. LUC, BELGIUM, 3INSTITUT JULES BORDET, UNIVERSITÉ LIBRE DE BRUXELLES, BELGIUM, 4OSLO UNIVERSITY HOSPITAL, NORWAY, 5UNIVERSITY COLLEGE LONDON HOSPITAL, UK, 6HAUKELAND UNIVERSITY HOSPITAL, NORWAY, 7CENTRE FOR CANCER BIOMARKERS (CCBIO), UNIVERSITY OF BERGEN, NORWAY, 8INSTITUT CURIE, PARIS, FRANCE, 9THE CHRISTIE NHS FOUNDATION TRUST, MANCHESTER, UK, 10FRANCE LABORATORY OF INTEGRATIVE CANCER IMMUNOLOGY, INSERM, PARIS, FRANCE, 11HALIODX, MARSEILLE, FRANCE, 12LYTIX BIOPHARMA, NORWAY, 13KINGS COLLEGE, GUY´S HOSPITAL, LONDON, UKAim• Evaluate the safety and tolerability of intra-tumoral LTX-315  in monotherapy or in combination with either ipilimumab or pembrolizumab  in patients with transdermally accessible tumors• Determine the recommended phase II dose and scheduleLTX-315 is a first in class oncolytic peptide with unique “release and reshape” MoACONFIDENTIALLTX-315 is a fir t in class oncolytic peptide with unique «release and reshape» MoA1-9Preclincial studies of LTX-315 demonstrates complete regression of injected and non-injected tumors (i.e. Abscopal effect)Immune related response (irRC) assessmentMono VAGINAL SCCMono HEAD AND NECKMono SARCOMACombination BREASTMono BREASTCombination MELANOMAMono MELANOMALTX-315 converts cold tumors to hotTreatmentNo. of patients treatedNo. of patients with biopsies evaluable for CD8 IHC to dateNo. of patients with increased CD8+ T cells in post treatment tumorsLTX-315 28 17 15 (88%)LTX-315 + Pembrolizumab 9 5 4 (80%)CONFIDENTIAL 10melanoma leiomyo-sarcoma melanoma epidermoid cancer desmoid tumor breast cancerTumor type010203040506070321015 471010 321012 331030 472011 441013Treatment # patientstreated# patients with biopsiesevaluable for CD8 IHC  to date# patients with increasedCD8+ T cells in post treatment tumorsLTX-315 28 17 15 (88%)LTX-315 + Pembrolizumab 6 3 3 (100%)Increase in CD8 gene expression in tumors upon LTX-315 treatmentLTX-315 converts cold tumors to hotfold increaseCD8aTumor type100600020500Fold increase CD8aMelanoma Breast cancerDesmoid tumorEpidermoid cancerMelanomaLeiomyo-sarcomaIncrease in CD8 gene expression in tumors upon LTX-315 treatmentHierarchical Clustering of Immunosign® 21 Immune Gene Signature (HalioDx) which profiles expressions of a pre-defined set of effector T cell, Th1, chemokine, and cytokine genes.Gene expression in tumor pre and post treatmentDuration of treatment (weeks)LTX-315: Safety (N=51)Study DesignPrimary Endpoints • Safety (including DLTs, AEs, SAEs, lab assessments) of LTX-315Secondary Endpoints• LTX-315 related Immune parameters in tumor and peripheral blood • Anti-tumor activity of LTX-315 by CT scan assessment (immune-related response criteria (irRC))*AEs occuring in ≥ 2 patients per CTC Version 4.0# No grade 4 LTX-315 related AEs reported ¥ Reported as both LTX-315 and Pembrolizumab relatedPatient population• Advanced/metastatic disease (all tumor types)  • At least one transdermally accessible lesion of ≤ 10 cm in diameterLTX-315 Monotherapy  (N=36)*LTX-315 related  adverse eventGrade 1-2 (No. of pt (%))Grade 3-4# (No. of pt (%))Hypotension 10 (28%) -Parasthesia 8 (22%) -Rash 10 (28%) -Flushing 8 (22%) -Pruritis 4 (11%) -Tumor pain 2 (6%) 2 (6%)Allergic reaction 1(3%) 4 (14%)Pain (injection site) 2 (6%) 2 (7%)LTX-315 Combination therapy  (Ipilimumab/pembrolizumab) (N=15)LTX-315 related  adverse eventGrade 1-2 (No. of pt (%))Grade 3-4# (No. of pt (%))Allergic reaction 4 (29%) 1 (7%)Pain (injection site) 3 (20%) 1 (7%)Tumor pain 2 (13%) -Fatigue 2 (13%) -Pneumonitis¥ - 1 (7%)LTX-315 MonotherapyLTX-315 dose per injection No. of patients Tumor type Single/sequential lesion injection2-7mg (1-2 injections per lesion) 23 Melanoma (7); Breast (6); Sarcoma (3); H&N (3); Adrenal (1); Urethral (1); Desmoid (1); Pancreas Multiple (≥ 1) lesion injection3mg (1-8 injections per lesion) 8 Head & Neck; Breast; Vaginal SCC; melanoma; sarcoma (2); Anal Ca; Desmoid 4mg (1-6 injections per lesion) 5 Head & Neck (2);Anal Ca; Sacroma; Gastric caLTX-315 + Ipilimumab Metastatic melanoma  (post-PD1/L1 treatment; multiple (≥ 1) lesion injection)LTX-315 dose per injection No. of patients3mg (1-4 injections per lesion) 4LTX-315 + PembrolizumabMetastatic Triple Negative Breast Cancer (2-5th line);  multiple (≥ 1) lesion injection)LTX-315 dose per injection No. of patients3mg (1-2 injections per lesion) 44mg (1-6 injections per lesion) 5CD3D.goodTreatment status472011-prePRF1.good441013-preGZMK.good321012-preCD8A.good321009-preCXCR3.good471010-preCD69.good321009-postCCR2.good331030-preCD3E.good321015-preSTAT4.good472011-postICOS.goodGZMB.good321015-postIL15.good321012-postCXCL10.good331030-postCXCL11.good471010-postCD3G.goodTBX21.good441013-postGZMM.goodIRF1.goodGZMA.goodCCL2.goodSTAT1.goodLTX-315 generates a systemic tumor specific immune responseCase study: patient 471-016, Breast cancer, MonotherapyTumor pre treatment• 128 T cell clones expanded in blood post treatment.• Clones expanding in blood were predominantly detected in post-treatment tumor samples.Tumor pre treatmentCD8Tumor post treatmentCD8Tumor post treatmentT cell clones in blood post treatmentContracted in bloodContracted in blood  & present in tumorExpanded in bloodExpanded in blood  & present in tumorNo significant change in frequencyNot significant & in tumor1▪ 128 T cell clones expanded in blood post treatment.Contracted in bloodContracted in blood & present in tumorExpanded in bloodExpanded in blood & present in tumorNo significant change in frequencyNot significa t & i  tumorLTX-315 generate a systemic tumor specific immune responseCase study: patient 471-016, Breast cancer, Monotherapy▪ Clones expanding in blood were predominantly present in treated tumor.T CELL CLONES IN BLOOD PRE TREATMENTTUMOR PRE TREATMENT TUMOR POST TREATMENT T CELL CLONES IN BLOOD PRE TREATMENTT CELL CLONES IN BLOOD POST TREATMENTT CELL CLONES IN BLOOD POST TREATMENT▪ 128 T cell clones expanded in blood post treatment.Contracted in bloodContracte  in blood & present in tumorExpanded in bloodExpanded in blood & present in tumorNo significant change in frequencyNot significant & in tumor▪ Clones expanding in blood were predominantly present in treated tumor.T CELL CLONES IN BLOOD PRE TREATMENTT CELL CLONES IN BLOOD PRE TREATMENTT CELL CLONES IN BLOOD POST TREATMENTT CELL CLONES IN BLOOD POST TREATMENTT cell clones in blood pre treatmentT cell clones in blood pre treatmentT cell clones in blood post treatmentT cell clones expanded in blood are detected in post-treated tumors• Clones expanding in blood are detected in post-treatment tumor biopsies; median 49%, 6 patients analyzed.• In contrast, the expansion of pre-treatment-tumor associated clones is less in all but one patient; median 23%. • Contracted clones in blood were not detected in the tumor in 2 of the 6 patients. 300 μm 300 μmCONFIDENTIALFI I LirSDirPDirPRNot evaluableDuration of treatmentMelanoma (Mono and Combo)Breast (Mono and Combo)Sarcoma (Mono)Head and Neck (Mono)Vaginal SCC (Mono)CONFIDENTIAL4032241680Tumor-associated clones expanded in blood (median)Tumor-associated Clones (Proportion)ContractedExpandedT cell clones expanded in blood are detected in post-treated tumors1▪ Approximately 49% (median) of clones expanding in blood are detected in post-treatment tumor biopsies (6 patients analyzed).▪ In contrast, the expansion of pre-treatment-tumor associated clones is less in all but one patient (median 23%).▪ Contracted clones in blood were not detected in the tumor in 2 of the 6 patients. 020806040PostPreStudy Conclusions• LTX-315 converts “cold” tumors to “hot”, as evidences by increase of tumor infiltrating lymphocytes (CD8+ T cells) and gene expression analysis.• TCR clonality analysis of blood and tumors samples show that LTX-315 generates a systemic anti-tumor T cell response. • LTX-315 is generally safe and tolerable. No MTD has been reached.• Stable disease (SD) by irRC observed with LTX-315 mono therapy (8/15 pts)• Durable SD by irRC observed (1/4 pts) with LTX-315 + ipilimumab (32 wks, ongoing)• Partial Remission (PR) by irRC observed (1/8 pts) with LTX-315 + pembrolizumab (10 wks, ongoing)• Results support the rationale and potential benefit of LTX-315 as a novel intratumoral immunotherapy; A phase II multi-arm combination trial is planned in 2018

LTX‐315, an oncolytic peptide converts "cold" tumors to "hot" in a majority of patients with advanced cancer: results from an ongoing phase I study

http://discovery.ucl.ac.uk/10039831/1/lytix_biopharma-SITC_poster.pdf

LTX‐315, an oncolytic peptide converts "cold" tumors to "hot" in a majority of patients with advanced cancer: results from an ongoing phase I study

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