Alligator Bioscience Ab · OMXSTO:ATORX
Alligator Bioscience Ab — Redeye Life Science Seminar (November 2017)
17 slides from Alligator Bioscience Ab's conference presentation, November 2017
Slide 1: Alligator Bioscience AB (publ)
ALLIGATOR BIOSCIENCE AB (PUBL) November 2017 Per Norlén, CEO 1
Slide 2: Disclaimer
Disclaimer This presentation regarding Alligator Bioscience AB (“Alligator”) and its contents are confidential and may not be reproduced, redistributed or passed on, directly or indirectly, to any other person or published, in whole or in part, by any medium or for any purpose. This presentation doe
Slide 3: Tumor-directed immuno-oncology
Tumor-directed immuno-oncology GENERAL IMMUNE-ACTIVATION TUMOR-DIRECTED IMMUNE-ACTIVATION General immune activation is associated with risk of Selective activation of tumor-specific immune cells severe adverse effects results in systemic immunity with limited toxicity 3
Slide 4: Drug development pipeline
Drug development pipeline Research Pre-clinical development Phase I Phase II ADC-1013 (CD40) Partnered with Janssen Biotech Inc., developed as JNJ-7107 ATOR-1015 (OX40-CTLA4) ATOR-1017 (4-1BB) ALG.APV-527 (4-1BB-TAA) co-developed with Aptevo Therapeutics Inc. (TNFRSF-ND) TNFRSF: Tumor Necrosis Facto
Slide 5: ADC-1013 targeting CD40
ADC-1013 targeting CD40 ADC-1013 Mode of Action Immuno-modulating receptors ANTIGEN-PRESENTING CELL T CELL ANTIGEN-PRESENTING CELL T CELL ADC-1013 PDL1 or PDL2 ? + PDL1 or PDL2 PD1 – CD40 + CD80 or CD86 CD28 CD80 or CD86 CTLA4 – B7RP1 ICOS + B7-H3 ? – B7-H4 ? – HVEM BTLA – KIR – MHC class I or II TC
Slide 6: First-in-human clinical phase I
First-in-human clinical phase I ADC-1013 intratumoral dose escalation every 14 days to evaluate safety and tolerability in patients with advanced solid tumors Status: > 1st patient dosed April, 2015 > Five clinical centers in Sweden, Denmark and UK > Study completed March 2017, 24 patients enrolled
Slide 7: Demographics
Demographics Administration route Intratumoral IV Dose level (µg/kg) 22.5 75 200 400 75 Number of patients dosed 3 4 3 8 5 Age median (years) 67.0 62.5 74.0 59.0 60.0 Sex: Male/Female 3/0 2/2 2/1 3/5 4/1 Tumor type Colon/Rectal cancer 1 3 3 2 Melanoma 1 1 Kidney 2 2 Bile duct 1 1 Breast 1 Ovarian 1
Slide 8: Results ADC-1013 clinical phase I
Results ADC-1013 clinical phase I ADC-1013 is well tolerated by cancer > A second clinical phase I study is patients at clinically relevant doses ongoing, performed by Janssen Biotech, Inc., > Adverse events mainly low grade > Approx. 50 patients enrolled to date and transient > Intravenous dose esc
Slide 9: Immuno-oncology market and pipeline
Immuno-oncology market and pipeline Compound Company Indication Phase Target Yervoy® (ipilimumab) Bristol-Myers Squibb Melanoma M CTLA-4 > Approx. 70 immuno- Keytruda® (pembrolizumab) Merck Melanoma, lung cancer, H&N cancer M PD-1 oncology antibodies in Opdivo® (nivolumab) Bristol-Myers Squibb Melan
Slide 10: ATOR-1015: Dual binding to OX40 and CTLA-4
ATOR-1015: Dual binding to OX40 and CTLA-4 Design and optimization of the CTLA-4 binding part Anti-OX40 ATOR-1015 Anti-CTLA-4 5 mutations were introduced Affinity increased 100-fold T-cell T-cell ACTIVATION OF DEPLETION OF EFFECTOR T-CELLS REGULATORY T-CELLS ATOR-1015 SUPPRESSION OF REGULATORY T-C
Slide 11: ATOR-1015 promotes cell-to-cell interactions
ATOR-1015 promotes cell-to-cell interactions 11
Slide 12: ATOR-1015: In vitro synergy
ATOR-1015: In vitro synergy ATOR-1015 induces ADCC on CTLA-4/OX40 expressing T-reg Synergistic T-reg depletion 140 120 ADCC (fold induction) 100 80 T-reg 60 40 Macrophage 20 0 > ATOR-1015 kills regulatory T-cells (ADCC) 0.001 0.01 0.1 1 10 100 1000 Conc. log (nM) ATOR-1015 > ATOR-1015 is superior to
Slide 13: ATOR-1015 anti-tumor efficacy
ATOR-1015 anti-tumor efficacy Survival bladder cancer (MB49) Tumor-specific long-term immunity Tumor volume (mm3) Survival (%) ATOR-1015 demonstrates anti-tumor efficacy in multiple tumor models: bladder, colorectal, melanoma and pancreas 13
Slide 14: Tumor-directed suppression of regulatory T cells
Tumor-directed suppression of regulatory T cells ATOR-1015 increases Teff/Treg ratio in tumor ATOR-1015 does not affect systemic T-cells Colon carcinoma model CD8/Treg ratio tumor (fold change) e r ab 5 ct cl 01 hi m 4 -1 A- Ve 0 R x4 TL O O C AT ATOR-1015 activates the immune system in tumors, but
Slide 15: ATOR-1015 positioning
ATOR-1015 positioning > Next generation CTLA4 antibody with augmented T-reg depletion > First in class dual immune activator > Expected synergy with PD-1 > Excellent bispecific format > Clinical trial in cancer patients starts 2018 15
Slide 16: Strong immuno-oncology pipeline
Strong immuno-oncology pipeline Targets: CD-40 CTLA-4 x OX-40 4-1BB 4-1BB x 5T4 N.D. x TNFR-SF 16
Slide 17: Alligator Bioscience
ALLIGATOR» bioscience www.alligatorbioscience.com
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