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Omptas: Outer Membrane Protein Targeting Antibiotics Antibiotic Guardian Conference June 27Th, 2018 in London, United Kingdom

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Omptas: Outer Membrane Protein Targeting Antibiotics Antibiotic Guardian Conference June 27Th, 2018 in London, United Kingdom OMPTAs: Outer Membrane Protein Targeting Antibiotics Antibiotic Guardian Conference June 27th, 2018 in London, United Kingdom. Dale GE: June 27th 2018, Antibiotic Guardian Conference. London, United Kingdom Disclaimer Forward looking statements This presentation does not constitute or form part of, and should not be construed as, an offer or invitation or inducement to subscribe for, underwrite or otherwise acquire, any securities of Polyphor Ltd. (“the Company” and together with its subsidiary, “we”, “us” or the “Group”), nor should it or any part of it form the basis of, or be relied on in connection with, any contract to purchase or subscribe for any securities of the Group, nor shall it or any part of it form the basis of, or be relied on in connection with, any contract or commitment whatsoever. Certain statements in this presentation are forward-looking statements, beliefs or opinions, including statements relating to, among other things, the Company's business, financial condition, future performance, results of operation, potential new market opportunities, growth strategies, and expected growth in the markets in which the Group operates. In some cases, these forward-looking statements may be identified by the use of forward-looking terminology, including the terms “targets”, “believes”, “estimates”, “anticipates”, expects”, “intends”, “may”, “will” or “should” or, in each case, their negative or other variations or similar expressions. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial consequences of the plans and events described herein. Actual results may differ materially from those set forth in the forward-looking statements as a result of various factors (including, but not limited to, future global economic conditions, changed market conditions, intense competition in the markets in which the Group operates, costs of compliance with applicable laws, regulations and standards, diverse political, legal, economic and other conditions affecting the Group’s markets, and other factors beyond the control of the Group). Neither the Company nor any of its respective directors, officers, employees, agents, affiliates, advisors nor any other person is under any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. You should not place undue reliance on forward-looking statements, which speak of the date of this presentation. Statements contained in this presentation regarding past trends or events should not be taken as a representation that such trends or events will continue in the future. Some of the information presented herein is based on statements by third parties, and no representation or warranty, express or implied, is made as to, and no reliance should be placed on, the fairness, accuracy, completeness or correctness of this information or any other information or opinions contained herein, for any purpose whatsoever. This presentation is intended to provide a general overview of the Group’s business and does not purport to deal with all aspects and details regarding the Company and the Group. This presentation is furnished solely for your information, should not be treated as giving investment advice and may not be printed or otherwise copied or distributed. The information contained in this presentation is not to be viewed from nor published, distributed or reproduced in nor taken or transmitted, in whole or in part, directly or indirectly, into the United States of America ("United States), its territories or possessions, Australia, Canada or Japan or any other jurisdiction where such publication, distribution or offer is unlawful, and does not constitute an offer of securities for sale in any of these jurisdictions. The securities offered by the Company have not been, and will not be, registered under the U.S. Securities Act of 1933, as amended (the “Securities Act”), or the securities laws of any state or other jurisdiction of the United States and such securities may not be offered or sold within the United States, except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and applicable state or local securities laws. This presentation does not contain or constitute an offer of, or the solicitation of an offer to buy or subscribe for, securities to any person or in any jurisdiction to whom or in which such offer or solicitation is unlawful. Dale GE: June 27th 2018, Antibiotic Guardian Conference. London, United Kingdom 2 New antibiotics (Gram-negative) on the horizon Enterobacteriaceae Non-fermenters Novel Compound Company Market Clinical trials MoA ESBL KPC OXA MBL MDR-PA MDR-AB Ceftolozane-tazobactam Merck No cUTI, cIAI HAP/VAP (P3) Y Partial cIAI, cUTI, Ceftazidime-avibactam Pfizer No Y Y Y HAP/VAP Meropenem-vaborbactam Melinta No cUTI HAP/VAP (P3) Y Y Y Aztreonam-avibactam Pfizer No cIAI & HAP/VAP (Ph3) Y Y Y Partial Imipenem/cilastin-relabactam Merck No HAP/VAP (P3) Y Y Partial Cefiderocol Shionogi No cUTI, HAP/VAP; BSI (P3) Y Y Y Y Y Partial Plazomicin Achaogen No cUTI, BSI (under review) Y Y Y Partial Sulopenem Iterum No cUTI, UTI (P3) Y Eravacycline Tetraphase No cIAI (P3) Y Y Y Y Partial Ceftaroline-avibactam Pfizer (halted?) No cUTI (P2) Y Y Y Cefepime-AAI101 Allecra No cUTI (P2) Y Y Y LYS-228 Novartis No cIAI, cUTI (P2) Y Y Y Partial Meropenem-nacubactam Roche No Phase 1 Y Y Partial Partial Cefepime-zidebactam Wockhard Partial Phase 1 Y Y Y Y Y Y VNRX-5133 VenatoRX Partial Phase 1 Y Y Y Y Piperacillin-AAI101 Allecra No Phase 1 Y Y Y SPR-741 Spero Partial Phase 1 Partial Partial Partial Partial Partial Partial GSK-3342830 Glaxo No Phase 1 Y Y Y Y Y Partial AIC-499 + unknown BLI AiCuris No Phase 1 Y Y Y Partial Partial Partial EXT2514 + sulbactam Entasis No Phase 2 Y Y Y TP-6076 Tetraphase No Phase 1 Y Y Y Y Y Murepavadin Polyphor Yes HAP/VAP (P3) Y OMPTA Polyphor Yes Pre-clinical Y Y Y Y Y Y Dale GE: June 27th 2018, Antibiotic Guardian Conference. London, United Kingdom 3 The discovery of murepavadin Protegrin I POL0067 POL6137 POL7001 murepavadin Pseudomonas specific! PK/ADMET optimization ~ 300 ~ 300 analogues analogues Protegrin I POL0067 POL6137 (1ZY6) ~ 500 analogues murepavadin POL7001 ~ 700 analogues Srinivas, S., et al. (2010) Science, 327: 1010 – 1012 Murepavadin an antibiotic against Pseudomonas aeruginosa with a new target and mode of action Dale GE: June 27th 2018, Antibiotic Guardian Conference. London, United Kingdom 4 Murepavadin targets selectively and potently Pseudomonas Potent in vitro activity against Pseudomonas aeruginosa strains Type Strain ATCC/DSM MIC (µg/mL) Pseudomonas aeruginosa ATCC 27853 0.06 Pseudomonas aeruginosa PAO1 0.25 Pseudomonas putida DSM 291 0.06 Pseudomonas fluorescens DSM 6147 0.06 Pseudomonas aureofaciens ATCC 15926 0.06 Pseudomonas syringae ATCC 12271 0.008 Escherichia coli ATCC 25922 >64 Klebsiella pneumoniae ATCC 13883 >64 Acinetobacter baumannii ATCC 19606 >64 Burkholderia cepacia ATCC 25416 >64 Stenotrophomonas maltophilia ATCC 13637 >64 Staphylococcus aureus ATCC 29213 >64 Dale GE: June 27th 2018, Antibiotic Guardian Conference. London, United Kingdom 5 Murepavadin: Targeted and Novel mechanism of action Murepavadin binds both to LPS and to LptD Murepavadin LptD Target LptD pharmacophore1 pharmacophore 2 OMP binding LPS binding . Genetic studies reveal LptD as the potential target of Murepavadin (Science, 2010) . Photo-affinity labeling studies confirm LptD as the target (Science, 2010) . High affinity binding to the periplasmic domain of LptD demonstrated (ACS Chemical Biology, 2018) Both pharmacophors are essential for the potent activity of murepavadin Dale GE: June 27th 2018, Antibiotic Guardian Conference. London, United Kingdom 14 Murepavadin MIC Data Surveillance data (n=1,219) from Europe and USA (2014) and China (2012-2013) including 30.1% MDR pathogens 1 000 800 600 400 Murepavadin target MIC Number of Isolates of Number 200 0 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 ≥32 MIC (mg/L) 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 ≥32 n=1,219 25 92 983 93 15 5 2 0 2 1 1 Cum % 2.1 9.6 90.2 97.9 99.1 99.5 99.7 99.7 99.8 99.9 100.0 There is little difference between geographies or MDR and non-MDR MIC Source: Company information distributions Dale GE: June 27th 2018, Antibiotic Guardian Conference. London, United Kingdom 7 Murepavadin: MIC Data in XDR (extensively drug- resistant isolates Surveillance data of 785 XDR isolates from Europe (n=353) and USA (432) collected in 2016-17 Number of isolates (cumulative %) inhibited at murepavadin MIC (mg/L) of: XDR* isolates (n) ≤0.06 0.12 0.25 0.5 1 2 4 >4 All XDRs (n=785) 169 (21.5) 362 (67.6) 190 (91.8) 38 (96.7) 8 (97.7) 8 (98.7) 4 (99.1) 7 (100) Colistin-R (n=50) 16 (10.0) 16 (42.0) 28 (98.0) 1 (100) Ceftolozane-tazobactam-R (n=231) 58 (25.1) 100 (68.4) 57 (93.1) 10 (97.4) 1 (98.8) 2 (98.7) 0 (98.7) 3 (100) Tobramycin-R (n=412) 93 (22.6) 204 (72.4) 95 (95.1) 13 (98.3) 4 (98.3) 3 (100) R: Non-susceptible based upon EUCAST Clinical Breakpoint Tables v. 7.1, valid from 2017-03-10 * Defined by Magiorakos et al, 2012, Cin. Microbiol. Infect. 50 (6.4%) of the XDR isolates are Colistin-resistant. 231 (29.4%) of the isolates are ceftalozane-tazobactam-resistant 412 (52.4%) of the isolates are Tobramycin resistant Murepavadin exhibited potent activity against a large collection of clinical XDR isolates of P.
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