Slide 1: R&D Update
R&D UPDATE ALLIGATOR 27 August 2020
Slide 2: Disclaimer
Disclaimer FORWARD LOOKING STATEMENTS This presentation contains forward-looking statements that provide Alligator’s expectations or forecasts of future events such as new product developments, regulatory approvals and financial performance. Such forward looking statements are subject to risks, unce
Slide 3: Agenda
Agenda 2:00 p.m. Company introduction and clinical development update ATOR-1015 and mitazalimab Per Norlén, CEO 2:15 p.m. ATOR-1017 – Concept and latest news Malin Carlsson, COO 2:30 p.m. 4-1BB – An attractive target for cancer immunotherapy Professor Ignacio Melero, University of Navarra, Pamplona,
Slide 4: Company highlights
Company highlights 1 Advanced immuno-oncology company with an innovative technology platform that has produced 4 clinical-stage programs to date 2 ATOR-1015: first-in-class tumor-localizing antibody with potential to replace current CTLA-4 treatment 7e3 3 ATOR-1017: best-in-class tumor-localizing 4-
Slide 5: Planned clinical readouts through 2022
Planned clinical readouts through 2022 ✓ Interim safety data readout for Phase I ATOR-1015 study (Q2 2020) 2020 ✓ Interim readout ATOR-1017 (Q3 2020) ❑ Readout for Phase I ATOR-1015 study (Q4 2020) ❑ Readout for Phase I ATOR-1017 study (H1 2021) 2021 ❑ Efficacy data readout for Phase Ib ATOR-1015 st
Slide 6: ATOR-1015: First-in-class tumor-localizing CTLA-4 x OX40 bispecific
ATOR-1015: First-in-class tumor-localizing CTLA-4 x OX40 bispecific A safer and more efficacious CTLA-4 targeting antibody Clinical opportunity Phase I started in March 2019. Currently Clinical Status evaluating doses of 12 mg/kg Clinical Efficacy readout Phase Ib mono study Tumor Tumor killing Deve
Slide 7: ATOR-1015: Supportive interim Phase I data at AACR/ASCO
ATOR-1015: Supportive interim Phase I data at AACR/ASCO > Cancer types: > Colorectal cancer (n=9) > Uveal melanoma (n=2) > Pancreatic cancer (n=2) > Ovarian cancer (n=2) > Cholangiocarcinoma, Gastric cancer, Cutaneous melanoma, Gallbladder cancer, Cervix cancer, Non small cell lung cancer (n=1 for e
Slide 8: ATOR-1015: Clinical development path
ATOR-1015: Clinical development path > Phase I dose evaluation ongoing, readout at medical conference in Q4 2020E > Phase Ib expansion starts H2 2020E to assess single agent efficacy in melanoma. Planned efficacy readout H2 2021E > Phase II combination with anti-PD-1 in melanoma with interim efficac
Slide 9: Mitazalimab: Phase II ready CD40 antibody
Mitazalimab: Phase II ready CD40 antibody Unleashing the power of dendritic cells in IO Phase I complete Phase II/III, pancreatic cancer T cell Other indications: renal, H&N, bladder, lymphoma (DC) Tumor cell Clinical status Phase II ready CD40 agonist antibody Preclinical and clinical data package
Slide 10: Clinical validation for CD40 in pancreatic cancer
Clinical validation for CD40 in pancreatic cancer CD40 increases cold tumors’ response rates ORR NP=nab-paclitaxel 60 60 60 40 40 40 20 20 20 0 0 0 1 em em 1 0 D PD D4 +P G G +C P+ + em 40 em N +G D +G +C NP NP em Van Hoff et al NEJM O´Hara et al AACR, Wainberg et al J Clin +G 2013 Abstr. CT004, 201
Slide 11: Mitazalimab vs main competitors
Mitazalimab vs main competitors Mitazalimab APX-005M ABBV-927 SEA-CD40 Selicrelumab CDX-1140 Fc IgG1 IgG1 IgG1 IgG1 IgG2 IgG2 Fc-mod. (S267E) Fc-mod.(V273Y), Fc-mod., Improved Improved FcgRIIb, Reduced ADCC FcgRIIIa reduced ADCC FcγR-dependent Yes Yes Yes Yes No No Dose (MTD) 1.2 mg/kg 0.1-0.3 mg/kg
Slide 12: Mitazalimab vs main competitors
Mitazalimab vs main competitors Mitazalimab APX-005M ABBV-927 SEA-CD40 Selicrelumab CDX-1140 Fc IgG1 IgG1 IgG1 IgG1 IgG2 IgG2 Fc-mod. (S267E) Fc-mod.(V273Y), Fc-mod., Improved Improved FcgRIIb, Reduced ADCC FcgRIIIa, reduced ADCC FcγR-dependent Yes Yes Yes Yes No No Dose (MTD) 1.2 mg/kg 0.1-0.3 mg/k
Slide 13: Mitazalimab vs main competitors
Mitazalimab vs main competitors Mitazalimab APX-005M ABBV-927 SEA-CD40 Selicrelumab CDX-1140 Fc IgG1 IgG1 IgG1 IgG1 IgG2 IgG2 Fc-mod. (S267E) Fc-mod.(V273Y), Fc-mod., Improved Improved FcgRIIb, Reduced ADCC FcgRIIIa reduced ADCC FcγR-dependent Yes Yes Yes Yes No No Dose (MTD) 1.2 mg/kg 0.1-0.3 mg/kg
Slide 14: OPTIMIZE-1: Mitazalimab in Pancreatic Cancer
OPTIMIZE-1: Mitazalimab in Pancreatic Cancer Establish safety and efficacy with Folfirinox Dosing regimen: Folfirinox 2 days before mitazalimab > Run-in part to demonstrate safety of mitazalimab in combination with standard of care > Expansion at selected dose (RP2D) with an additional 20 patients f
Slide 15: Mitazalimab: Clinical development path
Mitazalimab: Clinical development path > Current status: Phase I completed, Phase II ready > Phase II combination with chemotherapy, mFOLFIRINOX, in pancreatic cancer with planned CTA Q4 2020. PD-1 to be added upon efficacy response. > Interim readout H2 2021E > Efficacy readout, H2 2022 2020 2021 2
Slide 16: ATOR-1017 – Concept and latest news
ATOR-1017 – Concept and latest news 16
Slide 17: ATOR-1017 – designed for optimal efficacy and safety
ATOR-1017 – designed for optimal efficacy and safety A tumor-directed 4-1BB antibody Phase I Phase II Phase I readout: (DC) H1 2021 • Superior safety/efficacy profile vs other 4-1BB Best-in-class antibodies Unique • Unique 4-1BB domain design • IgG4 for tumor-directed effect > Activates 4-1BB expres
Slide 18: 4-1BB is a Key Immuno-Oncology Target
4-1BB is a Key Immuno-Oncology Target > Highly expressed on tumor specific T cells and on NK cells > Induces effective tumor killing and long-term immunity > Target preclinically validated, signs of effect in clinical studies > Several antibodies in clinical development > Potential to increase respo
Slide 19: ATOR-1017 – the optimal 4-1BB mAb
ATOR-1017 – the optimal 4-1BB mAb ATOR-1017 was designed to overcome limitations observed with other 4-1BB antibodies Toxicity issues * Good efficacy Poor efficacy MTD ~ 0.1 mg/kg Good tolerability Well tolerated MTD≥10 mg/kg *Clinical development with urelumab was discontinued in phase II, due to l
Slide 20: ATOR-1017 binds to a unique epitope
ATOR-1017 binds to a unique epitope 4-1BB domain mapping ATOR-1017 antibody format Urelumab (BMS) Domain 2- binding ATOR-1017 Binds to 4-1BB Utomilumab (Pfizer) Stabilized Activates IgG4 (S228P) immune system 20
Slide 21: ATOR-1017 Lead generation
ATOR-1017 Lead generation ALLIGATOR-GOLD® Library FIND® optimization of ATOR-1017 with optimized • Phage library ATOR-1017 manufacturability • Diversity >1010 Binding to target domain of Improved temperature stability 4-1BB Reduced aggregation Desired agonistic function propensity ❑ Optimiza
Slide 22: Binding to the right domain on the 4-1BB receptor is crucial
Binding to the right domain on the 4-1BB receptor is crucial ATOR-1017 Crystal structure 22
Slide 23: ATOR-1017 – The story of molecular engineering to hit the sweetspot
ATOR-1017 – The story of molecular engineering to hit the sweetspot Different molecular properties give different effect Antibody Urelumab Utomilumab ATOR-1017 CTX-471 (Compass) Domain (CRD) 1 3/4 2 3/4 Clinical effect Superagonist effect Weak effect, Anticipated: Unknown effect Toxicity no clinical
Slide 24: ATOR-1017 Clinical Data
ATOR-1017 Clinical Data A first-in-human, multicenter, open-label, phase 1 study in patients with advanced solid malignancies to evaluate the safety of intravenously administered ATOR-1017 Short Title: ATOR-1017 first-in-human study Sponsor: Alligator Bioscience AB 24
Slide 25: Phase I study overview
Phase I study overview > A dose-ranging study that will comprise up to 50 patients with metastatic cancer, conducted at three different clinics in Sweden > Uppsala University Hospital > Karolinska University Hospital > Skånes University Hospital, Lund > Patient population: > Solid malignancies > Adv
Slide 26: ATOR-1017: Phase I interim readout
ATOR-1017: Phase I interim readout Encouraging safety profile > Dose-escalation ongoing, 40 mg flat dose has been cleared, next dose is 100 mg > 7 patients have been dosed and all are still on-study > Few drug related adverse events have been observed and all were mild or moderate (grade 1 or 2). Pa
Slide 27: ATOR-1017 Clinical Data (Pharmacokinetics, PK)
ATOR-1017 Clinical Data (Pharmacokinetics, PK) > Data from first dosing occasion for 5 dose cohorts, first cycle > Cmax (Top concentration) and AUC (Area Under Curve) increase with dose Concentration over time after first infusion Serum conc (g/mL) ATOR-1017 100 40 mg (n=3) 10 15 mg (n=1) 1 5 mg (n
Slide 28: ATOR-1017: Clinical development plan
ATOR-1017: Clinical development plan > Phase I open-label dose escalation study ongoing with safety data readout H1 2021E > Expected to enrol up to 50 patients with metastatic cancer at three Swedish clinics > Patients will be receiving ATOR-1017 every 3 weeks > Primary endpoints: safety & tolerabil
Slide 29: 4-1BB, an attractive cancer target
4-1BB, an attractive cancer target Professor Ignacio Melero, Universidad Navarra 29
Slide 30: Alligator Bioscience
ALLIGATORSY bioscience