Lytix Biopharma - Developing novel cancer immunotherapies Investor - PowerPoint PPT Presentation

Lytix Biopharma - Developing novel cancer immunotherapies Investor Presentation , January 2017

2 Lytix Biopharma – Developing novel cancer immunotherapy  Vision – leading R&D company in the field of cancer immunotherapy  Private R&D focused company based in Oslo  Founded in Tromsö 2003 by Professors John Sigurd Svendsen and Öystein Rekdal  Technology platform derived from research on host defense peptides – ‘’nature’s own defense mechanisms’’  Focus on cancer since 2012  Business model – develop projects trough phase II, and partner for late stage development and commercialization  Strong IP - broad patent portfolio with patent cover until 2034

3 LTX-315 – first-in-class oncolytic peptide immunotherapy • LTX-315 makes cold tumors hot and responsive to immune checkpoint Inhibitors (ICIs) by releasing Unique an extended range of tumor specific antigens product • Strong pre-clinical anticancer activity and increased efficacy with ICIs • Ideal combination partner for ICIs – potential to augment efficacy without adding significant toxicity • Potential treatment in multiple, large indications Block buster • Targeting malignant melanoma, breast cancer and follow-on indications potential • Blockbuster potential with sales exceeding 1 billion USD • Clinical evidence of anti-tumor and immune effects presented at ECC2015 • Clinical evidence Stable disease (irRC response criteria) – 50% (8/16) median duration of stable disease: 14 weeks • Significant infiltration of CD8+ T-cells – 76% (13/17) patients

4 The Nordic landscape of immuno oncology  The competitive landscape is rapidly changing, with several different compounds currently being tested in target indications  The companies below have developed different technologies to fight cancer – the real race is abut finding successful combinations with checkpoint inhibitors which is expected to result in high deal-making activity Nature of therapy Clinical phase Lytix Biopharma Oncolytic Peptide Phase I Alligator Bioscience Antibody-based Phase I Immunicum Vaccine Phase II Targovax Vaccine-based & Virus-based Phase I/II Bioinvent Antibody-based Phase I/II LTX-315 represents a novel approach, making “cold” tumors “hot”

5 Cancer remains a major medical need Sales of cancer drugs 2015-2022  Largest therapeutic area with 11% of total drug sales  Cancer incidence is expected to grow – Every year, 14 million people are diagnosed with 200 cancer 180  160 Main pillars of therapy 140 – Surgery, radiation, chemo, hormonal and targeted 120  Large clinical need for better treatments 100 – 8.2 million deaths annually 80 60 40 20 0 2015 2022

6 Complex diseases require dynamic treatments Cancer immuno-therapy  The role of the immune system is to defend the body against threats e.g. bacteria, cancer  The immune system works in a variety of ways  Cancers hide and constantly transform to trick the immune system resulting in a constant “power struggle” between the immune system and the cancer  Immune oncology helps the immune system to fight cancer by boosting or breaking different mechanisms  A diverse response from the immune system is likely to be more successful to win over the disease

7 ICIs – the first wave in cancer immunotherapy  With ICI’s, immune oncology has taken center stage in the pharmaceutical industry becoming an attractive oncology segment Yervoy (BMS) Tecentriq Keytruda (MSD) (Roche/Genente ch 2011 2012 2013 2014 2015 2016 2017 2018 2019 Durvalumab (AstraZeneca) Avelumab (Merck / Pfizer) Opdivo (BMS)

8 ICIs – a paradigm shift in cancer treatment Next wave is to develop combinations ICI’s : significant progress but no silver bullit  Checkpoint Inhibitors have revolutionised cancer treatment • The success of immunotherapies has changed the way cancers today representing the new backbone of cancer treatment are being treated • Combinations of immunotherapies have shown significant higher response rate than monotherapy Anti-CTLA4 and anti-PD1 clinical data in adv. melanoma Non- Grade 3/4 AE’s Proportion alive ICIs Responders responders (side effects) Immune therapy combination Yervoy 20% 80% 20-30% Long term survival Opdivo 40% 60% 10-20% Immune therapy monotherapy Keytruda 33% 67% 10% Long term survival Combination Chemotherapy / radiation therapy Untreated of Yervoy and 58% 42% 55% Opdivo Time from treatment Source: EvaluatePharma (2016)

9 ICI’s allow T -cells to attack cancer by removing the brakes ICI’s Tumor specific = Increase the activity of T-cells T-cell activation Removing the brakes

10 ICIs: Data indicates efficacy only in ”hot” tumors Few effector T cells  ASCO/ESMO data confirms most tumours are ” cold ”, non -T-cell inflamed, lacking effector cells (CD8+)  ICIss require a T-cell inflamed tumor microenvironment for efficacy (”hot” tumor)  Major unmet clinical need – optimising immunotherapy Many effector T cells – Increase efficacy by inducing T-cell inflamed tumor microenvironment (hot tumors) – Checkpoint inhibitor therapy allows immune responses to eliminate cancer cells (Fig modified from Sharma, and James P. Allison, Science 2015 )

11 LTX-315 enabling checkpoint inhibitors ” cold ” tumours to ”hot” ICIs does not work in cold tumors LTX-315 will make cold tumors hot and enhance the proportion of cancer patients responding to ICIs Padmanee Sharma, and James P. Allison, Science 2015;348:56-61

LTX-315 unique MoA – making cold tumors hot LTX-315 releases potent immune stimulants and a broad repertoire of tumor antigens Zhou, Cell Death & Disease 2016. Zhou, Oncotarget 2015. Forveille, Cell Cycle 2015. Eike, Oncotarget, 2015. Camilio, OncoImmunology 2014, Camilio, Cancer Immunol Immunother, 2014

LTX-315 expands T-cell clonality in treated tumors Enhances immune responses to tumor antigens  The diversity of T-cell clones is significantly enhanced in LTX- 315 treated tumors versus untreated tumors  Each T-cell clone recognizes different tumor antigenes  LTX-315 induces release of neo-antigenes that some of the T-cell clones generated recognize Cancer model: Murine B16 melanoma. Adaptive Biotech’s TCR sequencing platform ( immunoSEQ)

LTX-315 and tumor heterogenity  Tumor heterogenity limits the efficacy of therapies  By injecting LTX-315 in multiple lesions a broader and more representative tumor antigen repertoire is presented for T-cells Fig from Jamal-Hanjani, Clin.Cancer Res, 2015

15 Pre-clinical data: LTX-315 induces systemic immune response Eliminates non-treated tumors 2 nd tumor 3 rd tumor v Control 1st 2 nd LTX-315 v 3 rd Days  The effect on distant tumors demonstrates an immediate systemic immune response  Treated animals showed no tumor growth after being re-challenged up to 14 months later Source: data on file, manuscript in preparation

16 LTX- 315: Preclinical synergy with immune checkpoint inhibitors  Efficacy of immune checkpoint inhibitors require Anti-CTLA-4 and LTX-315 – inflamed tumor microenvironment – immune responses to neoantigens Placebo  LTX-315 creates LTX-315 Anti-CTLA-4 – inflamed tumor microenvironment Anti-CTLA-4 + LTX-315 – immune responses to neoantigens  LTX-315 and immune checkpoint inhibitors may be an ideal combinations Yamasaki et al, Cell Death & Differentiation, 2016

17 Phase I - LTX-315 anti-tumor activity confirmed in patients Melanoma Patient (inj.lesion) Ongoing open phase 1, typical ph1 patient population, different cancer types, dose escalation, multilesion injections Complete and partial regression of injected lesions • 31% (8/26) of injected lesions Baseline After treatment Sarcoma patient (inj. lesion) Stable disease (irRC response criteria) • 50% (8/16) median duration of stable disease: 14weeks Significant infiltration of CD8 + T-cells • 76% (13/17) patients After treatment: Hot tumor Before: Cold tumor Increase of CD8 + T-cells Few CD8 + T-cells * Data on file, study ongoing

Phase I – LTX-315 makes “cold” tumors “hot”

Phase I – Patient case report indicating abscopal effect LTX-315 induces SD* after progression on antiPDL1  38 yr female, metastatic adrenocortical Ca (lung,liver peritoneal, bone metastasis) diagnosed in yr 2000  Multiple prior treatments: surgery (primary & met lesions), chemotherapy, radiotherapy  Treatment prior to LTX-315: antiPDL1 (ICI) Baseline biopsy: Week 6 biopsy: 7 LTX-315 Large left flank lesion Large left flank lesion injections (non Injected) (non Injected) Tumour size (SPD on CT) 6 mths 7 injections treatment 5 wk 5 wk interval aPDL1 LTX-315 Time on treatment Adrenal carcinoma No viable tumor cells ABSCOPAL EFFECT * SD: Stable Disease (irRC criteria)

20 Clinical development program LTX-315 2015 2016 2017 2018 2019 2020 H1 H2 H1 H2 H1 H2 H1 H2 H1 H2 H1 H2 MONOTHERAPY TRIALS Mixed indications Ph I Single lesion Phase I Multiple lesions Phase I (20) COMBINATION TRIALS Interim. LPI FPI. FPI. data Malignant melanoma Phase I Phase II Phase II F/UP Prep. Prep (2nd Line) PhI/II LTX-315 + anti-CTLA-4 TNBC (2-4th line) Ph I/II Phase II F/UP Prep. Phase I Prep Phase II LTX-315 + anti-PD-1 Undisclosed project Prep. Phase II Study preparation Enrolment and treatment Esc; Dose escalation phase Exp; Expansion phase