Advancing the Frontiers of mab mixtures

Transcription

1 Advancing the Frontiers of mab mixtures...unlocking the power of the immune system Symphogen Corporate Presentation June 216 Symphogen/1

2 Symphogen Overview Privately held company employees Headquarters in Ballerup, DK Clinical Development in NJ, US Next-generation mab therapeutics World s leading mixture experience Differentiated pipeline with novel MoA s EGFR mixture (Sym4) in Phase 2 MET mixture in Phase 1 Pan-HER mixture towards Phase 1 Value Creating Collaborations with significant non-dilutive financing Strong Investor Base Genentech Phase 1 infectious disease program Baxalta immuno-oncology collaboration Pro-forma cash position of 24 million 8 June, 216 Symphogen/ 2

3 Innovative Oncology Pipeline of mabs & mab Mixtures mcrc 3 rd /4 th line Proprietary Programs EGFR MET Pan-HER Sym4 Sym15 Sym13 mcrc 2 nd line mcrc ECD mutation Glioblastoma 2 nd line ESCC/SCCHN SqNSCLC (1 st /2 nd line) w/ PD-1 MET amplified tumors Pancreatic, NSCLC Partnered Programs I/O Check Points Infect. Disease TBA Sym9 Undisclosed Undisclosed 8 June, 216 Symphogen/ 3

4 Sym4: 1 st -in-class Anti-EGFR mab Mixture our most advanced program in multiple trials 992 EGFR 124 Symphogen/4

5 Sym4 Product Overview Synergistic mixture of two chimeric IgG1 mabs against non-overlapping epitopes on EGFR Domain III Manufactured as individual mabs at 2,L scale; formulated as single drug product COGS/mg similar to conventional mab Patent protection until 228/229 8 June, 216 Symphogen/ 5

6 Synergistic Effect of Two mab s Clear synergistic inhibition by Sym4 mixture in vivo and in vitro Tumor regression, sustained tumor suppression induced by Sym Treatment period 5 mg/kg total dose twice weekly Control mab 8 June, Days post inoculation 992 mab Cetuximab 124 mab A431NS, Epidermoid carcinoma (vulva), EGFR amplified Sym4 (Pedersen et al. Cancer Research, 21, 7(2) ) Symphogen/ 6

7 Clinical Benefit Documented in Anti-EGFR Resistant Pts PFS Size of tumor 8 June 216 9mg/weekly 12mg/weekly Dienstmann R et al Cancer Discovery June 215; 5; Symphogen/ 7

8 On-Going Phase 2b EGFR Resistant mcrc Trial Design Sym4 12 mg/kg/week, i.v., n=8 KRAS WT mcrc with acquired resistance to anti-egfr mabs (3rd/4th line) Sym4 9 mg/kg loading dose, 6mg/kg/week maintenance, i.v., n=8 Investigator s choice (BSC or Capecitabine or 5-FU), n=8 Open label, multi-center, randomized 1:1:1, controlled Phase 2b, blinded to sponsor 254 pts enrolled ; data expected 2H 216 Primary end-point: OS - powered to detect OS of 9 months. vs. 6 months (HR of.65 power 8%, alpha 2%) 8 June, 216 Symphogen/ 8

9 Sym4 Summary Strong preclinical data support development in both speed to market and expansion indications Clear anti-tumor activities demonstrated in Phase 1/2 studies Acceptable safety demonstrated for both weekly and q2wk dosing Strong scientific evidence supports benefit of combining with PD-1/PD-L1 (trial protocol under development) Market dynamics and product life cycle of existing marketed products create opportunity to advance into 1 st and 2 nd line therapy Biomarkers identified for patients with Squamous NSCLC and mcrc Indication PC M Expected news flow mcrc (3/4th line) mcrc (2nd line, FOLFIRI combo) mcrc ECD mutation Glioblastoma (2nd line) NSCLC (1/2 line) combo with I/O ESCC / SCCHN Phase 2b data end-216 Phase 1b/2a data mid-218 Phase 2 data end-217 Phase 2a data mid-218 Phase 2a data end-218 TBD 8 June, 216 Symphogen/ 9

10 Sym15/Anti-MET Symphogen/1

11 Sym15 Anti-MET 2 humanized IgG1 mabs produced in a single batch of drug substance Antibody pair selected for synergistic cancer cell growth inhibition, target internalization and degradation Balanced ratio (1:1) between mabs Preclinical data confirms selection of biomarker Phase 1 enrollment initiated in March June, 216 Symphogen/ 11

12 Sym15 Induces MET Down-Modulation In Vitro and In Vivo EBC-1 Lung 1 Treatment period 9 8 Vehicle Sym Collect 4 6 tumors Days post tumor inoculation 8 June 216 Symphogen/ 12

13 Sym15 Summary Pre-clinical data indicate strong activity in MET amplified models MET amplification expected to be effective biomarker Clean GLP tox studies Phase 1 patient enrollment on-going Dose-Escalation in patients with solid tumor malignancies to assess safety and tolerability of Sym15 Dose-Expansion in basket cohort of patients with MET amplified solid tumor malignancies to evaluate the antitumor effect (e.g. NSCLC, Gastric, RCC) Indication PC M Expected news flow Gastric, NSCLC, RCC Phase 1/2 data end June 216 Symphogen/ 13

14 Sym13 (Pan-HER): A Novel Multi-Targeting mab Mixture Symphogen/14

15 Sym13/Pan-HER Antibody Mixture Balanced ratio of antibody pairs (EGFR/HER2/HER3) Antibodies against each receptor selected for synergistic target downmodulation and cancer cell growth inhibition 6 humanized antibodies produced in a single batch of drug substance Late preclinical stage 8 June 216 Symphogen/ 15

16 Control,3 times weekly ip x1 Pan-HER, 5 mg/kg,3 times weekly ip x1 Striking Pan-HER Response in Patient Derived Xenograft (PDX) Models PDX models with mutated KRAS and known resistance to HER family targeted therapeutics Pancreatic Cancer H&N Cancer * ST191 Vehicle Pan-HER * ST ST179 * * ST * STS ST ST497B ST ST1261B STS59 15 STS64 15 STS58 15 ST ST334 6 ST1379B 25 ST ST939 2 ST * * * Lung Cancer 15 ST599 2 STS136 2 ST ST ST ST ST146 2 STS ST935B 15 STS June Study performed at START, TX Symphogen/ 16

17 Pan-HER Summary Down-regulates all 3 HER targets simultaneously Prevents compensatory receptor up-regulation Provides broader efficacy than targeting a single receptor or any combination of two receptors in the HER family Overcomes acquired resistance due to increased ligand production Effectively suppresses tumor growth in multiple preclinical PDX models Pancreatic cancer, TNBC, NSCLC, mcrc, SCCHN Clinical development Phase 1 followed by study expansion in 2 indications Indication PC M Expected news flow A novel Pancreatic, strategy NSCLCto improve efficacy and address Phase drug 1 initiation resistance H2 216 resulting from tumor heterogeneity and tumor plasticity 8 June 216 Symphogen/ 17

18 Partnerships Partnering rationale: External validation of I/O discovery platform / target External validation of technology platform within infectious diseases Deal value: Total potential deal value of 1.6 billion plus royalties on worldwide sales Total potential deal value may exceed USD1m plus royalties on worldwide sales Type: Worldwide option, research and licensing agreement Field: Oncology MRSA Symphogen product rights: None None Worldwide research and licensing agreement Partnership commenced: December 215 June 28 8 June 216 Symphogen/ 18

19 Equity Story Based on Broad and Mature Pipeline Multi-targeted approach to overcome treatment resistance Applies an established technology (mabs) in an innovative way Combination approach to overcome tumor escape mechanisms Potential to block multiple targets and to enhance cross-linking Mature pipeline that targets key indications Sym4 Phase 2b in mcrc as lead indication Additional clinical trials with Sym4 in multiple indications ongoing /planned Sym15 in Phase 1/2 development, Sym13 to enter clinic in the short-term Experienced management Multidisciplinary management team dedicated to Symphogen s success Extensive experience in both scientific and business management roles Renowned supervisory and scientific advisory boards Validating strategic partners Strategic partnership with Baxalta, 16m upfront, 1.4bn potential value Development partnership with Genentech, potential milestones ~ 1m Track-record of successfully establishing partnerships Key value inflection points ahead Read-out of Sym4 Phase 2b in lead indication anticipated end-216 Multiple read-outs of Phase 1 and Phase 2 trials anticipated in the mid-term Continuous updates expected from pipeline and partnering 8 June, 216 Symphogen/ 19

20 Symphogen Summary Clinical oncology pipeline of proprietary products Sym4; anti EGFR Novel MoAs vs. single EGFR mabs On-going trials in mcrc, ESCC & GBM Potential for accelerated approval Sym15; anti MET Phase 1 does escalation study initiated Q1, 216 Sym13; anti pan-her IND expected H2, 216 Value creating collaborations Genentech Ph1 infectious disease program Baxalta immuno-oncology collaboration Strong balance sheet with committed investors Raised a total of 316,5 m in committed capital through premier investors Pro-forma cash position is 24 million 8 June, 216 Symphogen/ 2

21 A Symphony of Natural Antibodies Contact: Kirsten Drejer, CEO Symphogen/ 21