Aura Biosciences, Inc. · NASDAQ:AURA
Aura Biosciences — Technical Presentation (May 2024)
20 slides from Aura Biosciences's technical presentation, May 24, 2024
Slide 1: Treatment of conjunctival melanoma cell lines with Bel-Sar induces immunogenic cell death
Treatment of conjunctival melanoma cell lines with Bel-Sar induces immunogenic cell death Sen Ma Ruben V. Huis In’t Veld, Elisabet de los Pinosa, Ferry A. Ossendorp, Martine J. Jager Departments of Ophthalmology and Immunology, LUMC, Leiden, The Netherlands AURA Biosciencesa, Boston, USA Insert > He
Slide 2: Disclosures
Disclosures S. Ma, (F); R.V. Huis in’t Veld, None; E. de los Pinosa, (O); F.A. Ossendorp, None; M.J. Jager (F), None The study was supported by Health Holland, The Netherlands and AURA Biosciencesa, Boston, USA Financial support (F), Owner(C) 2 Insert > Header & footer 24-May-24
Slide 3: Bel-sar is a novel precision immunotherapy
Bel-sar is a novel precision immunotherapy • Bel-sar o Virus-like Drug Conjugate (VDC) o Ongoing Phase 3 randomized clinical trial in small choroidal melanoma and indeterminate lesions • Bel-sar Mechanism of Action ▪ Local (suprachoroidal) administration of bel-sar and activation with infrared laser
Slide 4: Bel-sar: prior works
Bel-sar: prior works 1. Bel-sar specifically kills malignant tumor cells with a dual mechanism of action (Kines 2016) 2. Bel-sar has shown anti-tumoral activity in a rabbit orthotopic uveal melanoma model (Kines 2016) 3. Bel-sar: currently being investigated in a Phase 3 trial (NCT06007690) to treat
Slide 5: Conjunctival Melanoma (CJM)
Conjunctival Melanoma (CJM) • Conjunctival melanoma o Rare and malignant ocular tumor o BRAF and NRAS mutation • Current treatment: ▪ First line treatment for in situ CJM o Excision + cryotherapy to margins o Up to 50% local tumour recurrence ▪ Metastasis o 26% cases o Kinase inhibitors, Immune chec
Slide 6: Research Questions
Research Questions Can Bel-sar be used as an adjuvant to induce a stronger immune response to reduce recurrence rate or metastasis of CJM ? ▪ Transmembrane transport process of Bel-sar o Explore intracellular and subcellular localization of Bel-sar at different time points ▪ Test Bel-sar treatment i
Slide 7: Materials and methods
Materials and methods • CJM cell lines o Primary cell lines: CRMM1 (BRAF), CRMM2 (NRAS) o Recurrence cell line: CM2002.1 (BRAF) • Analyses: o Intracellular localization: immunofluorescence microscope o Cytotoxicity: FACS, MTS assay o Damage associated molecular patterns (DAMPs): CRT, HSP90 o Phagocy
Slide 8: Subcellular localization after addition to cells at 4° C for 4 hours
Subcellular localization after addition to cells at 4° C for 4 hours : only membrane binding Binding at 4 °C Uptake at 37°C Bel-sar binds to the membrane, even at 4°C 8 Insert > Header & footer 24-May-24
Slide 9: Bel-sar intracellular localization: 4h at 37 ° C
Bel-sar intracellular localization: 4h at 37 ° C Lysosome Golgi Mitochondria ER Tracker Bel-sar Merged Bel-sar appears in the lysosomes, Golgi 9 Insert > Header & footer 24-May-24
Slide 10: Intracellular location 8 hours after addition to cells
Intracellular location 8 hours after addition to cells Lysosome Golgi Mitochondria ER Tracker Bel-sar Merged Bel-sar is inside lysosomes, Golgi 10 Insert > Header & footer 24-May-24
Slide 11: Intracellular localization of Bel-sar 24 hours after addition to cells
Intracellular localization of Bel-sar 24 hours after addition to cells Lysosome Golgi Mitochondria ER Tracker Bel-sar Merged Bel-sar: mainly located in lysosome and partly in Golgi and Mitochondria 11 Insert > Header & footer 24-May-24
Slide 12: Intracellular localization of Bel-sar 24 hours after addition to cells, zoom in
Intracellular localization of Bel-sar 24 hours after addition to cells, zoom in Lysosome Golgi Mitochondria Tracker Bel-sar Merged Bel-sar in lysosome, Golgi and mitochondria 12 Insert > Header & footer 24-May-24
Slide 13: Transmembrane Process of Bel-sar
Transmembrane Process of Bel-sar 13 Insert > Header & footer 24-May-24
Slide 14: Binding of Bel-sar at 4 °C and 37 °C
Binding of Bel-sar at 4 °C and 37 °C Binding at 4 °C Uptake at 37°C Bel-sar binding and uptake increased over time and with concentration. At 37 ˚C (uptake), the gMFI was significantly higher than at 4 ˚C (binding). 14 Insert > Header & footer 24-May-24
Slide 15: Cell Viability and Cytotoxicity
Cell Viability and Cytotoxicity IC50 CRMM1: 40 pM CRMM2: 31 pM CM2005.1: 60 pM Bel-sar induced cell death in a concentration and fluence dependent manner. 15 Insert > Header & footer 24-May-24
Slide 16: Exposure of Damage Associated Molecular Patterns (DAMPs), Calreticulin (CRT) and HSP90 after Treatment with Bel-sar
Exposure of Damage Associated Molecular Patterns (DAMPs), Calreticulin (CRT) and HSP90 after Treatment with Bel-sar Bel-sar enhanced the membrane exposure of CRT and HSP90 16 Insert > Header & footer 24-May-24
Slide 17: Phagocytosis by THP-1 Derived Macrophages after treatment with Bel-sar
Phagocytosis by THP-1 Derived Macrophages after treatment with Bel-sar Bel-sar enhanced the phagocytosis of tumor cells by macrophages 17 Insert > Header & footer 24-May-24
Slide 18: Conclusions
Conclusions 1. Bel-sar binding was observed in all three CJM cell lines tested including primary and recurrent cell lines. 2. Bel-sar is distributed to lysosomes, Golgi and mitochondria. 3. Bel-sar induced effective cell death in the three CJM cell lines tested. 4. Bel-sar induced immunogenic cell d
Slide 19: Discussion and Next Steps
Discussion and Next Steps • Can Bel-sar induce other types of cell death? o Ferroptosis (lysosome related) o Pyroptosis ( Golgi, mitochondria) • Explore clinical development of Bel-sar in ocular surface and eyelid malignancies
Slide 20: Thank you
Thank you M.J. Jager R.V. Huis In’t Veld E. de los Pinos F.A. Ossendorp