Tromsø

Oslo

• Norwegian non-listed company

• Develops novel therapeutics within oncology

LTX-315 is an immunotherapy in Phase I/IIa

....improving nature´s owndefence mechanisms

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

LTX-315

Induces complete regression and prevents lung metastasis in a B16 melanoma model

LTX-315 has an effect on disseminated tumors

- Rapid onset of immune response -

1st 2nd

3rd

i.p.

Transformed mesenchymal sarcomas in PVG rats

Control

LTX-315

Membrane-active host defense peptides

Intratumoraladministration of

LTX-315

Immature DC

Antigen engulfment

Mature DC

Antigen presentation

Intradermal tumor

HMGB1

Antigens

ATP

LTX-315 induces lysis

of plasma and mitochondria membranes

Release of DAMPs from cytosol and

mitochondria

Production ofinflammatory

cytokinesfrom immune

cells

Target lesion

CTLs

Activation and augmentation of

tumor specific CTLs

Unique mechanism of action

Camilio et al. AACR 2014

Non-target lesion

Rapid disruption of the cell membrane

0 min 5 min 10 min 20 minTime:

Ultra rapid membrane disruption

NH

O

NH2

NH

O

NH

O

N

NH

O

NH2

NH

O

NH2

NH

O

NH

NH

O

NH2

O

NH

O

NH

NH2

NH2

NH2

OH

O

n

LTX-315De novo designed oncolytic peptide

LTX-315 is an immunotherapy in Phase I/IIa

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

Cohort Conc.(mg/mL)

Dose

1 10 10% of tumour volume

2 20 10% of tumour volume

3 202 mg 1st injection4 mg next injections

Weekly injections of LTX-315 into one transdermallyaccessible tumour for a maximum of 6 injections

Tumor-infiltrating lymphocytesBreast 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

Reduction of tumour volumeOccular melanoma – cohort 3

Baseline (14 x 6 mm) After 6 injections (10 x 4 mm)

By the courtesy of Olav Inge Håskjold, OUS

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 80Duration: Approximately 2 yearsClinical 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

Guy´s and St ThomasJames SpicerSanjeev Deva

Institut Jules BordetAhmad AwadaVakili JalalPhilippe Aftimos

UCL Saint-LucJean Francois BaurainFeby Marjuadi

DNR, OUS

Sites and Participants

Oslo

London

Brussels

C12-315-03

Patient No Site

Cohort 1

001 Oslo University Hospital

002 Oslo University Hospital

003 Guy’s Hospital, London

Cohort 2

004 Jules Bordet, Brussel

005 St. Luc, Brussel

006 St. Luc, Brussel

Cohort 3 007 St. Luc, Brussel

Preliminary data from cohort 1 and 2

Safety

– No issues

Efficacy

– Signs of response in injected tumors in cohort 2

Dose expansion phase

Potential study groups:– Melanomas

– Sarcomas

– Head and neck

– Metastasis

Sites in EU and US

18

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

Preliminary data with checkpointblockade inhibitors (CBIs)

Significant synergy obtained with thecombination of LTX-315 and anti-CTLA-4 in a sarcoma mouse model

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