March Company Introduction. Microbiome R&D and Business Collaboration Forum: Europe Myriam Golembo, VP Development

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1 March 2018 Company Introduction Microbiome R&D and Business Collaboration Forum: Europe Myriam Golembo, VP Development

2 Biomx At A Glance We are a microbiome drug discovery company developing customized phage therapies that target and destroy harmful bacteria in chronic diseases such as IBD and cancer Scientific Founders Investors Prof. Eran Elinav MD, PhD WIS Microbiome Prof. Rotem Sorek PhD WIS Phage-bacteria Defense Systems Prof. Timothy K Lu PhD MIT Synthetic Biology 8VC

3 Growing Evidence Of Harmful Bacteria Role In Chronic Diseases Gastric Cancer H. Pylori IBD Kleibsiella Colon Cancer Fuso Proven to be directly linked to gastric cancer Oct Dec Disease State Oct Induce Inflammation

4 Phage Evolved Naturally To Target And Destroy Specific Bacteria Specific to targeted bacterial strains Amplifying at target Self-limiting - replication dependent on host existence History of safety in humans Synthetic biology enhances phage attributes Expand host range Convert from lysogenic to strictlylytic Add additional payload e.g. anti-biofilm, CRISPR FDA Workshop, DC, July 2017 Key Takeaways Safety relies on phage attributes; no GLP healthy animal safety studies required Phase 1 can move straight to patients or carriers of target bacteria Phage have been approved in the past as GRAS

5 BiomX Technology Platform License Target Discovery Platform Acquisition - Target Discovery Platform License - Phage Discovery Platform License Phage SynBio Methods Target Discovery Phage Discovery Pre-Clinical /Clinical Confirmed Target - Identify bacterial target + functional validation Customized Phage Cocktail Cocktail optimization, in-vivo efficacy

6 Target Discovery Target Target Discovery Phage Discovery Pre-Clinical /Clinical Multiple Analysis Levels Metagenomics Metatranscriptome A. Bacteria Prevalence/Abundance High resolution strain detection (at <10^-5, exhaustive alignment, DeNovo assembly) B. Bacteria Growth Dynamics Novel algorithm based on replication rate to identify actively growing bacteria C. Response To Stimuli/MOA Differential RNA expression to characterize microbiome response to a given trigger

7 Phage Discovery Target Target Discovery Phage Discovery Pre-Clinical /Clinical Designing Customized Phage Cocktails Resistance Host Range Lysogenic/Lytic Harmful Genes Study Bacterial Mutations Structure/function of bacteria and phage Expand Host Range A. Phage Combinations B. Synthetic Biology Bacteria Phage Database Biofilm Degradation Formulation Other Evaluate Biofilm Degradation Capacity Biofilm Growth (white circles) Left Antibiotic Right Phage Cocktail Customized Phage Cocktail Long Term Stability Studies Developing formulations stable at room temp. for >1 year

8 Pipeline Focus On Chronic Diseases TARGET DISCOVERY MICROBIOME MODULATION PRE-CLINICAL DEVELOPMENT CLINICAL DEVELOPMENT IBD (Inflammatory Bowel Disease) BX002 GI Tract Related Cancers Immuno-Oncology (Checkpoint Inhibitors) Liver (e.g. PSC)

9 IBD Novel Pro-inflammatory Targets Addressing Disease Triggers Pro-inflammatory Kleibsiella Strains Oct Inflammatory Induction in GF Mice GF + 7 Other Mix GF + Target Strain TH1 IFN-g IFN-g Disease State Higher Abundance in IBD Patients Abundance of Klebsiella Pneumoniae strains Induce Inflammation % Relative Abundance Science (Atarashi et al. 358 (6361), )

10 IBD BX002 Phage Therapy In-Vitro In-Vivo Density - OD Target bacteria (no phage) BX002 Phage cocktail Time [hr] Single phage CFU/gr stool Eradication of KP after 1 KP2 in stool after x1 dose dose of of phage phage cocktail cocktail (day 5) group 1+3 group 2+4 KP2 untreated (group 1+3) KP2 + phage cocktail KP + phage cocktail (group 2+4) Provisional Patent Application filed Sep covering multiple phage clusters IND scheduled for H1 2019

11 A New Treatment Approach For IBD Patient A Patient B Stool Test Stool Test Bacteria Detected Various Phage Cocktails BX002 BX003 BX004 BX005

12 I/O - Motivation I/O Therapies Potential To Improve Response Rate The Microbiome Impacts Response Rates Cancer (e.g. Melanoma) Patient 30% Response 70% No Response Favorable/negative bacteria specie impact on melanoma progression in patients V. Gopalakrishnan et al., Science /science.aan4236 (2017)

13 I/O Novel Target Discovery Metagenomics Metatranscriptome Target Discovery Plan A. Bacteria Abundance high resolution strain detection B. Bacteria response to differential RNA expression Output: A. Key Bacteria B. Responding Genes Preliminary Results Colon Cancer Model Abundance / Response Responding Bacterial Genes (by treatment)* CTLA CTL4 +PD PD Genes *Significant change in expression compared to control at Fdr<0.1 Key Takeaways: 1 st time bacterial response reported for I/O High overlap between treatments suggests shared biological response

14 Proof of Mechanism in Acne A topical gel of a proprietary phage cocktail Customized cocktail penetrates biofilm BX001 on a lawn of P. acnes 1 No effect on other bacteria Cocktail 1 Cocktail 2 Cocktail Overcomes antibiotic resistance Activity amplified at target site No phage control 1 No phage control 2 Erythromycin Black Area BX001 gel applied Red Area of activity (eradication P.acnes) 4 Overcomes biofilms On track to first in human trials in H2 2018

15 Key Goals Going Forward 2018 IBD Program - IND ready Customized phage cocktail for GI tract cancers Immuno-oncology/liver Programs Identify bacterial targets and move to phage discovery SynBio generates improved phage to a key program Phage preliminary clinical POM (topical acne treatment)