Slide 1: New Developments in belzupacap sarotalocan (AU-011) in Ocular Oncology
ISOO 2022 New Developments in belzupacap sarotalocan (AU-011), an Investigational Virus-Like Drug Conjugate (VDC) in Ocular Oncology Exhibit 99.2
Slide 2: Legal Disclosure
Legal Disclosure This presentation contains forward-looking statements, all of which are qualified in their entirety by this cautionary statement. Many of the forward-looking statements contained herein can be identified by the use of forward-looking words such as "may", "anticipate", "believe", "co
Slide 3: Aura is Dedicated to Science and Supports Collaborative Research
Aura is Dedicated to Science and Supports Collaborative Research Cadmus Rich, MD Chief Medical Officer, Head of R&D Aura Biosciences Ruben Huis in ‘t Veld, MSc Leiden University Anneli Savinainen, MS VP, Head of Preclinical R&D Aura Biosciences Rhonda Kines, PhD Principal Scientist Aura Biosciences
Slide 4: Novel Oncology Platform Using Virus-Like Drug Conjugates (VDCs)
Novel Oncology Platform Using Virus-Like Drug Conjugates (VDCs) Ocular Oncology Opportunity to develop vision preserving therapy for early-stage choroidal melanoma Foundational Value Completed Phase 1b/2 trial: Positive data in key clinical endpoints FDA/EMA/MHRA are in alignment with pivotal trial
Slide 5: Pipeline Targeting Life-Threatening Cancers with High Unmet Needs
Pipeline Targeting Life-Threatening Cancers with High Unmet Needs Program OTHER SOLID TUMORS OCULAR ONCOLOGY Preclinical Phase 1 Phase 2 Pivotal Anticipated Milestones Choroidal Metastases (Breast, lung and other cancer metastases in the eye) Primary Choroidal Melanoma (Ph 1b/2 Intravitreal and Ph2
Slide 6: Choroidal Metastasis
Choroidal Metastasis aura
Slide 7: Targeted Oncology Platform - Virus-Like Drug Conjugates (VDCs)
Targeted Oncology Platform - Virus-Like Drug Conjugates (VDCs) Virus-Like Particles Conjugated to a Cytotoxic Payload to form the VDC VDCs can Recognize Tumor Associated HSPGs* Virus-Like Particle (VLP) Virus-Like Drug Conjugate (VDC) Cx Cytotoxic Drug Kines et al; International Journal of Cancer, 1
Slide 8: Belzupacap Sarotalocan (AU-011) Novel Dual Mechanism of Action
Belzupacap Sarotalocan (AU-011) is an Investigational VDC with a Novel Dual Mechanism of Action Phthalocyanine dye AU-011 Belzupacap sarotalocan (AU-011) is a novel VDC that consists of an HPV derived VLP conjugated to ~200 molecules of phthalocyanine dye AU-011 Demonstrated Positive Data in Phase 1
Slide 9: Potential to Target Tumors That Express HSPGs
Potential to Target Tumors That Express HSPGs Broad-based Tumor Targeting Mechanism by Virtue of the Binding to Tumor Specific HSPGs Knelson et al., Trends in Biochemical Sciences 2014; Fuster and Esko, Nature Reviews Cancer, 2005; Blackhall et al., British Journal of Cancer (2001) 85(8), 1094–1098;
Slide 10: Choroidal Metastasis – Background
Choroidal Metastasis – Background Unilateral (72%) Unilateral (72%) Solitary (72%) Choroidal location (88%) Choroidal Metastasis from non-small cell lung cancer4 C-Mets Originates from Multiple Primary Cancers1 ~20K eyes with choroidal metastases in the U.S. annually2 1Mathis et al. New concepts…cho
Slide 11: AU-011 Induced Potent Cytotoxicity in Multiple Human Cancer Cell Lines
AU-011 Induced Potent Cytotoxicity in Multiple Human Cancer Cell Lines Commonly Causing Choroidal Metastasis Breast (40-53%) EC50 = 58 - 118 pM Lung (20-29%) EC50 = 20 - 40 pM GI (4%) EC50 = 34 - 386 pM Kidney (2%) EC50 = 21 - 82 pM Prostate (2%) EC50 = 13 - 560 pM Skin (2%) EC50 = 5 - 113 pM AU-011
Slide 12: AU-011 Demonstrated Binding and Potent Cytotoxicity in Cancer Cell Lines
AU-011 Demonstrated Binding and Potent Cytotoxicity in Multiple Human Cancer Cell Lines Commonly Causing Choroidal Metastasis Breast Colon Renal AU-011 can bind to cancer cells and induced potent cell killing upon light activation Specificity was demonstrated by inhibition of HSPG’s binding by hepar
Slide 13: Single Administration of AU-011 Inhibited Tumor Growth and Prolonged Survival
Single Administration of AU-011 Inhibited Tumor Growth and Prolonged Survival in a Dose-Dependent Fashion – Breast Cancer Reduced Tumor Growth Prolonged Survival Breast Cancer In-Vivo (Syngeneic Mouse Model, EMT-6) Tumor cells were implanted subcutaneously. AU-011 treatment was initiated when tumors
Slide 14: Conclusion
Conclusion AU-011 can bind to, and kill, tumor cells derived from the most common cancer types known to metastasize to the choroid Binds to modified HSPG’s on the surface of cancer cells No cytotoxicity in the absence of light activation was observed AU-011 showed dose-dependent activity in vivo usi
Slide 15: Retrospective Matched Case-Control Study
Retrospective Matched Case-Control Study
Slide 16: Study to Evaluate Visual Acuity Outcomes of AU-011 vs. Plaque Radiotherapy
Subjects with lesion ≤3mm from the fovea or optic disc and received AU-011 treatment (IVT) in Ph1b/2 trial (n=43) Subjects treated with Plaque Radiotherapy (Planned ~129) rMCC* Study to Evaluate Visual Acuity Outcomes of AU-011 vs. Plaque Radiotherapy Matching criteria: baseline tumor thickness, LBD
Slide 17: rMCC Results – Statistically Significant Vision Preservation with AU-011
rMCC Results – Statistically Significant Vision Preservation with AU-011 vs Plaque Radiotherapy ^logMAR – logarithm of the minimal angle of resolution Change from Baseline in Vision Change from Baseline in logMAR^ AU-011 Plaque * p < 0.05; ** p < 0.001 D = 0.017 D = 0.244* D = 0.444** D = 0.691** D
Slide 18: rMCC Results – Loss of Lines of logMAR Vision
rMCC Results – Loss of 3 and 6 Lines logMAR Vision Source Timepoint Loss of logMAR of ≥ 0.3 Loss of logMAR of ≥ 0.6 % p-value % p-value AU-011 Last 23.3% - 14.0% - AU-011 vs. Plaque Year 1 25.7% 0.7627 12.2% 0.7338 Year 2 42.3% 0.0304 26.0% 0.3571 Year 3 53.3% 0.0020 35.1% 0.0419 Year 4 67.1% <.0001
Slide 19: AU-011 in Combination with Checkpoint Inhibitors
AU-011 in Combination with Checkpoint Inhibitors Ruben Huis in t’ Veld
Slide 20: Immune checkpoint inhibition combined with targeted therapy using a novel VDC
Immune checkpoint inhibition combined with targeted therapy using a novel virus-like drug conjugate Ruben Huis in ‘t Veld Research sponsored by Health Holland in collaboration with Aura Biosciences Cx Virus-Like Particle (VLP) Cytotoxic dye Virus-Like Drug Conjugate (VDC)
Slide 21: AU-011 novel mechanism of action
AU-011 is an investigational virus like drug conjugate with a novel mechanism of action Cancer cell directed cytotoxicity Induction of antitumor immune responses 22-jun-22
Slide 22: Rationale for combining AU-011 treatment and immune checkpoint inhibition
Rationale for combining AU-011 treatment and immune checkpoint inhibition Wykes M. N. & Lewin S. R. Immune checkpoint blockade in infectious diseases. Nature Reviews Immunology. 2018;18:91–104 Beyrend et al. (2019): PD-L1 blockade induces LAG-3 expression à Co-targeting of PD-L1 & LAG-3 22-jun-22
Slide 23: AU-011 has shown binding and uptake in multiple types of tumor cells
AU-011 has shown binding and uptake in multiple types of tumor cells AU-011 Cancer cells AU-011 22-jun-22
Slide 24: AU-011 + light activation can induce cancer cell death
AU-011 + light activation can induce cancer cell death 22-jun-22 Viable cell Apoptotic cell Dead cell Control AU-011 + Light activation
Slide 25: AU-011 treatment can induce cancer cell directed cytotoxicity
AU-011 treatment can induce cancer cell directed cytotoxicity Cancer cell Dendritic cell Control AU-011 only Light only AU-011 + Light activation
Slide 26: Damage-associated molecular patterns (DAMPs)
Damage-associated molecular patterns (DAMPs) Showalter A. et al. Cytokines in immunogenic cell death: Applications for cancer immunotherapy. Cytokine. 2017;97:123-132
Slide 27: Release of DAMPs following AU-011 treatment
Release of DAMPs following AU-011 treatment Showalter A. et al. Cytokines in immunogenic cell death: Applications for cancer immunotherapy. Cytokine. 2017;97:123-132
Slide 28: Dendritic cell maturation following AU-011 treatment
Dendritic cell maturation following AU-011 treatment
Slide 29: AU-011 + Light activation combined with ICI enhanced treatment response (1 of 2)
AU-011 + Light activation combined with ICI enhanced treatment response compared to either treatment alone (1 of 2) 22-jun-22
Slide 30: AU-011 + Light activation combined with ICI enhanced treatment response (2 of 2)
AU-011 + Light activation combined with ICI enhanced treatment response compared to either treatment alone (2 of 2)
Slide 31: Treatment of primary and distant tumors enhanced with ICI (1 of 3)
Treatment of primary and distant tumors was enhanced by AU-011 + Light activation with ICI versus either treatment alone (1 of 3) 22-jun-22
Slide 32: Treatment of primary and distant tumors enhanced with ICI (2 of 3)
Treatment of primary and distant tumors was enhanced by AU-011 + Light activation with ICI versus either treatment alone (2 of 3) 22-jun-22
Slide 33: Treatment of primary and distant tumors enhanced with ICI (3 of 3)
Treatment of primary and distant tumors was enhanced by AU-011 + Light activation with ICI versus either treatment alone (3 of 3) 22-jun-22
Slide 34: AU-011 + light activation with ICI enhanced response in primary and distant tumors
AU-011 + light activation with ICI enhanced treatment response versus either treatment alone in both primary and distant tumors AU-011 CTLA-4 PD-L1 LAG-3 LAG-3 + PD-L1 AU-011 & CTLA-4 AU-011 & PD-L1 AU-011 & LAG-3 AU-011 & LAG-3 + PD-L1 Control Tumor Volume **** **** **** **** **** **** **** **** **
Slide 35: Conclusions
Conclusions AU-011 + Light activation: Induced cancer cell-directed cytotoxicity Released DAMPs and induced maturation of antigen-presenting cells Combined with ICI using anti-PD-L1 & anti-LAG-3 antibodies showed potential to induce complete and lasting tumor responses in both primary and distant tu
Slide 36: Acknowledgements
Acknowledgements Insert > Header & footer Prof. Dr. M. J. Jager & Prof. Dr. F. Ossendorp Aura Biosciences Health Holland Leiden University Medical Center
Slide 37: Question & Answer
Question & Answer ” aura
Slide 38: Thank you!
ISOO 2022 Thank you! Confidential