LTX-315 is an immunotherapy in Phase I/IIa

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1 Tromsø...improving nature s own defence mechanisms Norwegian nonlisted company Oslo Develops novel therapeutics within oncology LTX-315 is an immunotherapy in Phase I/IIa

2 LTX-315 is an intratumoral cancer immunotherapy activates the immune system and break tumor tolerance via an unique mode of action eliminates both primary tumor and metastases induces long-lasting protective immune response

3 LTX-315 Induces complete regression and prevents lung metastasis in a B16 melanoma model

4 LTX-315 has an effect on disseminated tumors - Rapid onset of immune response - Control 1st 3 rd i.p. 2 nd LTX-315 Transformed mesenchymal sarcomas in PVG rats

5 Membrane-active host defense peptides

6 Unique mechanism of action Intratumoral administration of LTX-315 LTX-315 induces lysis of plasma and mitochondria membranes ATP Antigens Release of DAMPs from cytosol and mitochondria HMGB1 Intradermal tumor Production of inflammatory cytokines from immune cells Immature DC Target lesion Mature DC Antigen engulfment Nontarget lesion CTLs Activation and augmentation of tumor specific CTLs Antigen presentation Camilio et al. AACR 2014

7 Rapid disruption of the cell membrane Ultra rapid membrane disruption Time: 0 min 5 min 10 min 20 min

8 LTX-315 De novo designed oncolytic peptide NH 2 NH 2 N H 2 O N H O H N O N H NH O H N NH O N H O H N O N H N O H N O NH 2 NH 2 NH 2 NH 2 O OH n

9 LTX-315 is an immunotherapy in Phase I/IIa

10 A single centre study designed to evaluate safety profile and determine recommended dose Immunological responses to the injections were exploratory endpoints Clinical site: The Norwegian Radium Hospital Investigator: Dr. Paal Brunsvig No. of patients: 14 treated in three cohorts Patient population: 9 melanomas, 4 lymphomas, 1 breast

11 Weekly injections of LTX-315 into one transdermally accessible tumour for a maximum of 6 injections Cohort Conc. (mg/ml) Dose % of tumour volume % of tumour volume mg 1 st injection 4 mg next injections

12 Tumor-infiltrating lymphocytes Breast cancer patient cohort 3 Haematoxilin/Eosin staining CD8 + cytotoxic T-cells Presence of treatment-associated necrosis (left panel) and infiltration of immune cells (TILs) (right panel) By the courtesy of Marius Lund-Iversen, OUS

13 Reduction of tumour volume Occular melanoma cohort 3 Baseline (14 x 6 mm) After 6 injections (10 x 4 mm) By the courtesy of Olav Inge Håskjold, OUS

14 A phase I/IIa open-label, multi-centre, multi-dose, dose escalation study of LTX-315 in patients with transdermally accessible tumours Patients: Up to 80 Duration: Approximately 2 years Clinical sites: European investigators with clinical experience in cancer immunotherapy Primary endpoints Safety profile Tumour infiltrating lymphocytes Secondary endpoints Local effects Systemic immunological response PK profile Anti-tumour activity

15 Sites and Participants DNR, OUS Guy s and St Thomas James Spicer Sanjeev Deva Oslo London Brussels Institut Jules Bordet Ahmad Awada Vakili Jalal Philippe Aftimos UCL Saint-Luc Jean Francois Baurain Feby Marjuadi

16 C Patient No Site 001 Oslo University Hospital Cohort Oslo University Hospital 003 Guy s Hospital, London 004 Jules Bordet, Brussel Cohort St. Luc, Brussel 006 St. Luc, Brussel Cohort St. Luc, Brussel

17 Preliminary data from cohort 1 and 2 Safety No issues Efficacy Signs of response in injected tumors in cohort 2

18 Dose expansion phase Potential study groups: Melanomas Sarcomas Head and neck Metastasis Sites in EU and US 18

19 LTX-315 is an ideal combination with checkpoint blockade inhibitors (CBIs)

20 Preliminary data with checkpoint blockade inhibitors (CBIs) Significant synergy obtained with the combination of LTX-315 and anti-ctla-4 in a sarcoma mouse model

21 LTX-315 Oncolytic peptide with a unique mode of action Phase I/IIa clinical trial ongoing Significant synergy with CBIs in animal models Co-development partner

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