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

Lytix Biopharma

• Developing novel cancer immunotherapies

Investor Presentation , January 2017

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

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Clinical evidence Block buster potential Unique product

• Potential treatment in multiple, large indications
• Targeting malignant melanoma, breast cancer and follow-on indications
• Blockbuster potential with sales exceeding 1 billion USD
• LTX-315 makes cold tumors hot and responsive to immune checkpoint Inhibitors (ICIs) by releasing

an extended range of tumor specific antigens

• Strong pre-clinical anticancer activity and increased efficacy with ICIs
• Ideal combination partner for ICIs – potential to augment efficacy without adding significant toxicity

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LTX-315 – first-in-class oncolytic peptide immunotherapy

• Clinical evidence of anti-tumor and immune effects presented at ECC2015
• 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

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

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LTX-315 represents a novel approach, making “cold” tumors “hot” Alligator Bioscience Nature of therapy Immunicum Bioinvent Clinical phase Antibody-based Vaccine Antibody-based Targovax Vaccine-based & Virus-based Phase I Phase II Phase I/II Phase I/II Lytix Biopharma Oncolytic Peptide Phase I

Cancer remains a major medical need

• Largest therapeutic area with 11% of total drug sales
• Cancer incidence is expected to grow

– Every year, 14 million people are diagnosed with cancer

• Main pillars of therapy

– Surgery, radiation, chemo, hormonal and targeted

• Large clinical need for better treatments

– 8.2 million deaths annually

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2015 2022

20 40 60 80 100 120 140 160 180 200

Sales of cancer drugs 2015-2022

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Complex diseases require dynamic treatments

• 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 Cancer immuno-therapy

Yervoy (BMS) Keytruda (MSD) Tecentriq (Roche/Genente ch Durvalumab (AstraZeneca) Opdivo (BMS) 2011 2012 2013 2014 2015 2016 2017 2018 2019

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

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Avelumab (Merck / Pfizer)

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Untreated

Time from treatment Proportion alive

Long term survival Long term survival Chemotherapy / radiation therapy

Immune therapy combination

Immune therapy monotherapy

Next wave is to develop combinations

• Checkpoint Inhibitors have revolutionised cancer treatment

today representing the new backbone of cancer treatment

ICIs – a paradigm shift in cancer treatment

ICI’s: significant progress but no silver bullit

Source: EvaluatePharma (2016)

ICIs Responders Non- responders Grade 3/4 AE’s (side effects) Yervoy 20% 80% 20-30% Opdivo 40% 60% 10-20% Keytruda 33% 67% 10% Combination

• f Yervoy and

Opdivo 58% 42% 55%

Anti-CTLA4 and anti-PD1 clinical data in adv. melanoma

• The success of immunotherapies has changed the way cancers

are being treated

• Combinations of immunotherapies have shown significant

higher response rate than monotherapy

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ICI’s Increase the activity of T-cells

=

Removing the brakes Tumor specific T-cell activation

ICI’s allow T-cells to attack cancer by removing the brakes

ICIs: Data indicates efficacy only in ”hot” tumors

• 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

– Increase efficacy by inducing T-cell inflamed tumor microenvironment (hot tumors) – Checkpoint inhibitor therapy allows immune responses to eliminate cancer cells

10 (Fig modified from Sharma, and James P. Allison, Science 2015)

Few effector T cells Many effector T cells

LTX-315 enabling checkpoint inhibitors

”cold” tumours to ”hot”

11 Padmanee Sharma, and James P. Allison, Science 2015;348:56-61

ICIs does not work in cold tumors LTX-315 will make cold tumors hot and enhance the proportion of cancer patients responding to ICIs

LTX-315 unique MoA – making cold tumors hot

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 releases potent immune stimulants and a broad repertoire of 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 expands T-cell clonality in treated tumors

Enhances immune responses to tumor antigens

LTX-315 and tumor heterogenity

• Tumor heterogenity limits the efficacy
• f 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

Pre-clinical data: LTX-315 induces systemic immune response

Eliminates non-treated tumors

1st 2nd 3rd

• 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

Control LTX-315

v v

Days 2nd tumor 3rd tumor

Source: data on file, manuscript in preparation 15

Anti-CTLA-4 and LTX-315

Yamasaki et al, Cell Death & Differentiation, 2016

• Efficacy of immune checkpoint inhibitors require

– inflamed tumor microenvironment – immune responses to neoantigens

• LTX-315 creates

– inflamed tumor microenvironment – immune responses to neoantigens

• LTX-315 and immune checkpoint inhibitors may be

an ideal combinations

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Placebo LTX-315 Anti-CTLA-4 Anti-CTLA-4 + LTX-315

LTX- 315: Preclinical synergy with immune checkpoint inhibitors

Baseline After treatment

Before: Cold tumor Few CD8+ T-cells After treatment: Hot tumor Increase of CD8+ T-cells

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

Stable disease (irRC response criteria)

• 50% (8/16) median duration of stable disease: 14weeks

Significant infiltration of CD8+ T-cells

• 76% (13/17) patients

Melanoma Patient (inj.lesion)

17 * Data on file, study ongoing

Sarcoma patient (inj. lesion)

Phase I - LTX-315 anti-tumor activity confirmed in patients

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

Week 6 biopsy: Large left flank lesion (non Injected) Adrenal carcinoma No viable tumor cells 7 LTX-315 injections

LTX-315

5 wk interval 7 injections 5 wk 6 mths treatment

aPDL1

Tumour size (SPD on CT) Time on treatment

* SD: Stable Disease (irRC criteria)

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: Large left flank lesion (non Injected)

ABSCOPAL EFFECT

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 Multiple lesions

COMBINATION TRIALS

Malignant melanoma (2nd Line) PhI/II LTX-315 + anti-CTLA-4 TNBC (2-4th line) Ph I/II LTX-315 + anti-PD-1 Undisclosed project

Enrolment and treatment Study preparation Esc; Dose escalation phase Exp; Expansion phase

Phase I Phase I

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Prep. Phase II Phase II Prep. Phase II Phase II

FPI. FPI. LPI Interim. data

Phase I Phase I

(20)

Prep. Phase II Prep Prep F/UP F/UP

Clinical development program LTX-315

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Clinical Advisory Board

• Robert Andtbacka, M.D., associate professor in the Division of Surgical Oncology, University of Utah School of Medicine, U.S
• Sandra Demaria, M.D., professor of pathology and radiation oncology, Weill Cornell Medical College, NY, U.S
• Kevin Harrington, M.D., PhD., professor in biological cancer therapies, The Institute of Cancer Research, London, UK
• Aurélien Marabelle, M.D., PhD., clinical director of cancer immunotherapy program, Gustave Roussy, France

Scientific Advisory Board

• Guido Kroemer, M.D., PhD., professor of tumor cell biology, French Medical Research Council (INSERM), Gustave Roussy, France
• Laurence Zitvogel, M.D., PhD., professor of clinical oncology and tumor immunology, INSERM, Gustave Roussy, France

Collaboration is an important element in Lytix business strategy

Harvard University (M. Pittet)

• LTX-315`s ability to convert “cold” tumors to “hot” in genetically-engineered murine cancer models

Weill Cornell Medicine (Sandra Demaria)

• LTX-315 in combination with irradiation in poorly immunogenic mouse breast cancer models

IGR (L. Zitvogel and G. Kroemer)

• Investigate the capacity of LTX-315 to circumvent resistance to PD1 blockade using TLR agonists

OUS (G. Mælandsmo)

• Test LTX-315 in combination with two immuno-chemotherapeutic drugs (cyclophosphamide and doxorubicin)

Pipeline

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LTX-315 LTX-401 DTT

Monotherapy Combination therapy w/ICIs Undisclosed project All solid tumours Malignant melanoma Triple Negative Breast Cancer (TNBC) Undisclosed indication

PRECLINIC CLINIC

PLATFORM Transdermally accessible tumors ‘’cold to hot’’ Deep-seated tumours Deep-seated tumours PROGRAM

Wenche Marie Olsen, DrPhilos, COO

• Extensive senior leadership experience within research, development

and management of new drug products in pharmaceutical and biotech industry

• Former CEO of Lauras, various positions in Nycomed/GE Healthcare

Øystein Rekdal, PhD, Co-founder and CSO

• Former CEO of Lytix Biopharma (from establishment in 2003)
• Professor at the Medical Biochemistry at the University of Tromsø.

Extensive research background and is collaborating with several distinguished international institutions Andrew Saunders, CMO

• Trained as a haematologist with 25 years experience in heamato-
• ncology drug development in both clinical practice and industry
• Extensive industry experience including large pharma( Roche, Eli Lilly),

Biotech (Bioenvision) and founder and managing director of Linden Oncology Ltd, a specialist oncology consultancy. Kjetil Vangsnes, CFO

• MBA INSEAD, 20 years as CFO in listed and non-listed companies
• Background from industrial enterprises, medtech, oil services and

maritime shipping

Management Team

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Håkan Wickholm, CEO

• Extensive senior international leadership and management experience

from AstraZeneca

• Experience from Commercial roles across various therapeutic areas

including oncology and Strategic Business Development on both sell- and buy-side projects.

Gert W. Munthe, Chairman

• Founder and Managing Partner of Herkules Capital - a leading Nordic

private equity player. Chairman Pronova Biopharma 2004-2013.

• Extensive experience from both Norwegian and international

business - former CEO of Alpharma (listed on the NYSE), NetCom and Nycomed Imaging Knut Eidissen

• Owner and managing director of the consulting and investment

company Picasso

• Extensive experience as a board member from both private and

public companies, and strong track record in creating shareholder value Kari Grønås

• Extensive experience from pharmaceutical research and

development in Norwegian pharmaceutical companies

• Former Senior Vice President Operations in Algeta

Debasish Roychowdhury

• Oncologist with a background in R&D, regulatory affairs and

commercial operations. Former Global Head of Oncology at Sanofi with additional senior experience with GSK and Eli Lilly

• Acting CMO for Ra Pharmaceuticals, President of Nirvan Consultants

and serves in senior advisory roles for biotechnology companies Lena Torlegård

• Communication advisor since 1998, mainly dealing with financial,

corporate and crisis communication

• Has worked with a number of Life Science companies, and is

currently a member of the Board of Directors for Nanologica John Sigurd Svendsen

• Extensive research experience, and professor of organic chemistry at

the University of Tromsø

• Visiting scientist at several distinguished international institutions,

including the laboratory of Professor K.B. Sharpless (Nobel Laureate, Chemistry, 2000) at MIT Morten Jurs

• Extensive experience from the pharmaceutical sector as well as non-

executive experience from several board positions from both public and private companies

• Partner in Pegasus Industries AS, former CEO and CFO in Pronova

BioPharma

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Board of Directors

Shareholders

• Founders and board members control about 30% of

the shares

• The company has about 260 shareholders
• Incentive program representing approx. 7% of
• utstanding shares post transaction

Shareholders No Shares % NORTH MURRAY AS 160 572 16,0% PICASSO KAPITAL AS 122 189 12,2% TAJ HOLDING AS 78 519 7,8% CARE HOLDING AS 75 230 7,5% NORINNOVA INVEST AS 48 766 4,9% LYSNES INVEST AS 43 245 4,3% HOPEN INVEST AS 29 487 2,9% NORD I AS 27 329 2,7% 3 T PRODUKTER AS 25 730 2,6% 4 LB INVEST AS 17 812 1,8%

Top 10 628 879 62,8% Others 372 927 37,2% Total 1 001 806 100,0%

Ownership structure, per nov 2016

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Investment Case

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Potential first-in-class product that makes ”cold” tumors ”hot”

• Ideal combination partner for ICIs – making cold tumors hot
• LTX-315 has shown tumor-specific T-cell activation, increasing patients’ immune response
• Phase II trial expected to start Q1 2018

Boards and Management

• Strong Board and Management team with international pharmaceutical drug development and

commercial experience

• Prominent Scientific and Clinical advisory boards

An emerging immunocology leader

• LTX-315 is a first-in-class powerful oncolytic peptide immunotherapy
• Potential for multiple, high value indications resulting in block buster potential with sales > 1 bn USD
• Targeting a rapidly growing and developing market segment attractive to big pharma

Multiple value triggers

• Multiple shots on goal through program in 2 (3) indications
• Ongoing discussion regarding scientific collaborations for a new Phase II project
• 2 discovery projects underway