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

Lytix Biopharma - Developing novel cancer immunotherapies Investor presentation, March 2017

Lytix Biopharma in brief Company overview Key investment highlights  Private R&D focused company, based 1. Positioned in the fastest growing segment in pharma 1 in Oslo with revenue potential estimated to USD 30bn  Founded in 2003, main focus on cancer 1. First in class oncolytic peptide that triggers powerful 2 immunotherapy since 2012 stimulus of CD8+ T-cells 1. Mechanism of action stimulates broad T-cell repertoire  Technology platform derived from 3 that enables a multi-targeted attack on tumor research on host defense peptides – ‘’nature’s own defense mechanisms’’ 1. Clinical data from 42 patients, and with documented 4 anti-tumor effects  Strategy to develop projects trough phase II, and partner for late stage 5 1. Strong IP portfolio with granted patents lasting to 2034 development and commercialization

The key challenge in immuno-oncology is low response rates  Majority of cancer tumors are Non-responders Responders non-T-cell inflamed = cold 20 and do not respond to immune 33 40 checkpoint inhibitors  T-cell inflamed tumors = hot 80 may be effectively treated with 67 60 immune therapy  New drugs that can convert cold OPDIVO KEYTRUDA YERVOY tumors to hot are highly needed Malignant melanoma Source: Evaluatepharma (2016)

LTX-315 is a first-in-class oncolytic peptide that turns ‘’ cold tumors hot’’ Cold tumor with no T-cells Hot tumor with CD8+ T-cell infiltration Clinical trial with 28 patients:  Intra-tumoral treatment with LTX-315  75% of injected tumors turned hot 1 Baseline LTX-315 treated 1 CD8+ T-cell infiltration in 14 of 19 evaluable lesions

Medical need for cancer treatment continues to grow Background Revenue estimate cancer drugs 2015-2022, USD bn  Largest therapeutic area with 11% of total drug 200 sales 180  160 Cancer incidence is expected to grow 140 – Every year, 14 million people are diagnosed 120 with cancer 100  Main pillars of therapy is surgery, radiation, 80 chemo, targeted treatments 60  Immunotherapy introduced as a new modality 40  20 Large clinical need for better treatments 0 – 8.2 million deaths annually 2015 2022

The first wave in cancer immunotherapy is the Immune Checkpoint Inhibitors (ICIs) With ICIs, immune oncology has taken center stage in the pharmaceutical industry becoming an attractive oncology segment ICIs, Global revenue USD, million USD, billion Yervoy Keytruda Tecentriq (BMS) (MSD) (Roche/Genentech 2011 2012 2013 2014 2015 2016 2017 2018 2019 Durvalumab (AstraZeneca) Opdivo (BMS) Avelumab (Merck / Pfizer)

ICIs represent a paradigm shift in cancer treatment Next wave is to develop combinations ICIs: significant progress but no silver bullit  Checkpoint Inhibitors have revolutionized 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 Proportion alive Non- Grade 3/4 AE’s ICIs Responders Immune therapy combination responders (side effects) Yervoy 20% 80% 20-30% Long term survival Opdivo 40% 60% 10-20% Immune therapy monotherapy Long term survival Keytruda 33% 67% 10% Combination Chemotherapy / radiation therapy Untreated of Yervoy and 58% 42% 55% Opdivo Time from treatment Source: EvaluatePharma (2016)

LTX-315`s unique membranolytic activity results in a strong immunological response inducing «reshape and release» in tumor Immunological stimulus “accelerating” immune response – may be ideal combination with ICIs “removal of brakes” 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 induces an effective release of tumor antigens and immunostimulants 1. Induces immunogenic cell death of cancer cells 2. Disintegration of; • Mitochondria (high mutation rate and potent (DAMPS) • Other cytoplasmic organelles  Effective release of potent immunostimulants (DAMPs) and tumor antigens

10 One cancer tumor consists of several different cancer cells Cancer immunotherapy  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  Immunotherapy enables the immune system to fight cancer by boosting or breaking different mechanisms  A comprehensive response from the immune system is likely to be more successful to win over the disease Note: Only for illustration purposes. LTX-315 is currently not being explored for lung or brain cancer

LTX-315 effectively reprograms the tumor micro- environment (Preclinical data) Reduced number of immunosuppressive cells – Increased CD8+ T-cell in number and clonal diversity Tregs and MDSC Cancer model: Murine B16 melanoma. Adaptive Biotech’s TCR sequencing platform ( immunoSEQ)

12 LTX-315 induces complete regression in injected and non- injected lesions (preclinical data) 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

LTX-315 demonstrates synergy with immune checkpoint blockade in injected and non-injected tumors (preclinical data) Injected tumors Yamazaki et al., 2016, Cell Death and Differentiation

14 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 • 75% (14/19) patients Before: Cold tumor After treatment: Hot tumor Few CD8 + T-cells Increase of CD8 + T-cells

LTX-315 makes “cold” tumors “hot” in patients

Patient case report regression observed in non-injected tumors  38 yr female, adrenocortical cancer, diagnosed in year 2000. Metastasis to lung, liver, peritoneum, bone.  Multiple prior treatments: surgery (primary & met lesions), chemotherapy, radiotherapy  anti-PDL1 treatment prior to LTX-315 treatment Baseline biopsy: Week 6 biopsy: BASELINE +29.86% BASELINE +51.19% BASELINE +56.12% NADIR+16.42% NADIR+20.22% Large flank lesion Large flank lesion (28/12/2015) (28/12/2015) (non-injected) (non-injected) 350 TUMOUR SIZE (SPD ON CT) 300 250 7 LTX-315 200 injections 7 injections 6 mths treatment 5 wk 150 5 wk interval anti-PD-L1 LTX-315 100 Baseline Nadir Episode 3 Episode 4 21/08/2015 28/12/2015 08/03/2016 24/05/2016 Adrenal carcinoma No viable tumor cells TIME OF TREATMENT

17 LTX-315 clinical development program 2016 2017 2018 2019 H1 H2 H1 H2 H1 H2 H1 H2 Monotherapy, mixed tumors Phase I Single lesion Phase I Multiple lesions Combination Malignant melanoma LTX- Phase I Follow-up 315 + anti-CTLA-4 Breast cancer (TN) LTX-315 + Phase I anti-PD1 Phase II Phase II Combination Phase II Undisclosed project 1

Strong academic collaborations to further demonstrate LTX-315 anti-tumor effects LTX-315 ability to reprogram tumors Prof M. Pittet LTX-315 ability to circumvent resistance to PD1- blockade using TLR agonists Profs Zitvogel & Kroemer LTX-315 in combination with immuno- chemotherapy Prof G. Mælandsmo LTX-315 in combination with irradiation Prof S. Demaria

Lytix pipeline of new oncolytic peptides PLATFORM PROGRAM LTX-315 Monotherapy All solid tumours Transdermally Malignant melanoma accessible tumors Combination therapy w/ICIs Triple Negative Breast Cancer (TNBC) Undisclosed project ‘’cold to hot’’ Undisclosed indication Deep-seated LTX-401 tumours Deep-seated DTT tumours

Broad patent portfolio with protection until 2034 Other 1 Product Description EU US JP LTX-315 Methods-of-use claims Granted, expires 2019 3 granted, expires 2022 Granted expires 2019 AU, NO, CA Monotherapy Composition-of-matter Pending, expires 2029 Granted, expires 2032 Granted, expires 2029 AU, BR, CA, CN, IN, NZ, claims KR, RU, SG LTX-315 Methods-of-use claims 2 pending, expires 2 pending, expires Pending, expires 2034 PCT (not selected) Combination 2034 2034 T-cell clonality Methods-of-use claims NA NA NA PCT filed February 2017 LTX-401 Composition-of-matter Granted, expires 2030 Granted, expires 2030 Granted, expires 2030 AU, BR, CA, CN, IN, NZ, claims KR, RU, SG Technology (adaptive Methods-of-use claims Pending, expires 2027 2 granted, expires 2029 AU, CA, NO immunity) and 2020 1 Additional countries where patent is granted or pending