UNITED STATES
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FORM
CURRENT REPORT
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| Item 7.01 | Regulation FD Disclosure. |
On February 16, 2023, Aura Biosciences, Inc. (the “Company”) issued a press release titled “Aura Biosciences Announces Positive Interim Phase 2 Safety and Efficacy Data of Belzupacap Sarotalocan (Bel-sar) for the First-Line Treatment of Patients with Early-Stage Choroidal Melanoma with Suprachoroidal Administration at the Macula Society 46th Annual Meeting.” A copy of the press release is furnished herewith as Exhibit 99.1 and is incorporated herein by reference.
The information furnished under this Item 7.01, including Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
| Item 8.01. | Other Events. |
On February 16, 2023, the Company updated its corporate presentation for use in meetings with investors, analysts and others. A copy of the corporate presentation is filed as Exhibit 99.2 for purposes of Section 18 of the Exchange Act.
Forward Looking Statements
Statements contained under this Item 8.01 regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements about the initiation, timing, progress, results, and cost of our research and development programs and our current and future preclinical studies and clinical trials, including statements regarding the timing of initiation and completion of studies or trials and related preparatory work, the period during which the results of the trials will become available, and our research and development programs; our ability to successfully manufacture our drug substances and product candidates for preclinical use, for clinical trials and on a larger scale for commercial use, if approved; the ability and willingness of our third-party strategic collaborators to continue research and development activities relating to our development candidates and product candidates; our ability to obtain funding for our operations necessary to complete further development and commercialization of our product candidates; our ability to obtain and maintain regulatory approval of our product candidates; the size and growth potential of the markets for our product candidates, and our ability to serve those markets; our financial performance; the effect of the COVID-19 pandemic, including mitigation efforts and economic effects, on any of the foregoing or other aspects of our business operations, including but not limited to our preclinical studies and clinical trials and any future studies or trials; our ability to commercialize our products, if approved; and the implementation of our business model, and strategic plans for our business and product candidates.
Any forward-looking statements are neither promises nor guarantees, and investors should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond the Company’s control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements, including, without limitation, an improved quality of life of patients after treatment with belzupacap sarotalocan; a potential paradigm shift in the approach to the treatment of choroidal melanoma; the urgent need for a vision preserving targeted therapy; the potential of belzupacap sarotalocan compared to the existing standard of care for patients with choroidal melanoma; uncertainties inherent in clinical trials and in the availability and timing of data from ongoing clinical trials; the expected timing for submissions for regulatory approval or review by governmental authorities; the risk that the results of the Company’s clinical trials may not be predictive of future results in connection with future clinical trials; the risk that interim data from ongoing clinical trials may not be predictive of final data from completed clinical trials; whether the Company will receive regulatory approvals to conduct trials or to market products; whether the Company’s cash resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; risks, assumptions and uncertainties regarding the impact of the
continuing COVID-19 pandemic on the Company’s business, operations, strategy, goals and anticipated timelines; the Company’s ongoing and planned pre-clinical activities; and the Company’s ability to initiate, enroll, conduct or complete ongoing and planned clinical trials. These risks, uncertainties, and other factors include those risks and uncertainties described under the heading “Risk Factors” in the Company’s most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the U.S. Securities and Exchange Commission (“SEC”) and in subsequent filings made by the Company with the SEC, which are available on the SEC’s website at www.sec.gov. Except as required by law, the Company disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on the Company’s current expectations and speak only as of the date hereof and no representations or warranties (express or implied) are made about the accuracy of any such forward-looking statements.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits.
| Exhibit Number |
Description | |
| 99.1 | Press Release dated February 16, 2023, entitled “Aura Biosciences Announces Positive Interim Phase 2 Safety and Efficacy Data of Belzupacap Sarotalocan (Bel-sar) for the First-Line Treatment of Patients with Early-Stage Choroidal Melanoma with Suprachoroidal Administration at the Macula Society 46th Annual Meeting” | |
| 99.2 | Corporate presentation of the Company | |
| 104 | Cover Page Interactive Data (embedded within the Inline XBRL document) | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: February 16, 2023 | AURA BIOSCIENCES, INC. | |||||
| By: | /s/ Julie Feder | |||||
| Julie Feder | ||||||
| Chief Financial Officer | ||||||
Exhibit 99.1
Aura Biosciences Announces Positive Interim Phase 2 Safety and Efficacy Data of Belzupacap Sarotalocan (Bel-sar) for the First-Line Treatment of Patients with Early-Stage Choroidal Melanoma with Suprachoroidal Administration at the Macula Society 46th Annual Meeting
Boston, MA – Feb. 16, 2023 – Aura Biosciences, Inc. (“Aura”) (Nasdaq: AURA), a clinical-stage biotechnology company developing a novel class of virus-like drug conjugate (VDC) therapies for multiple oncology indications, today announced the presentation of positive interim Phase 2 safety and efficacy data of bel-sar with 9-10 months of follow up evaluating two key clinical endpoints: tumor control and visual acuity preservation using the suprachoroidal (SC) route of administration for the first-line treatment of patients with early-stage choroidal melanoma (indeterminate lesions and small choroidal melanoma (IL/CM)). The results were presented at the Macula Society 46th Annual Meeting held February 15-18, 2023, in Miami, FL.
“The data presented today with an average of nine months of follow up for patients treated with three cycles of therapy, show an excellent response to the therapy with 89-100% tumor control. In addition, the safety profile to date has been favorable with only one patient losing visual acuity and no treatment-related SAEs or significant AEs, which is encouraging given that the majority of these patients had tumors close to the fovea or optic disk and would have likely experienced severe and irreversible vision loss with the current standard of care with radiotherapy,” said Dr. Ivana Kim, Director of the Ocular Melanoma Center, Massachusetts Eye and Ear. “These latest results strongly support the potential of bel-sar to be used as a first line treatment option for patients with early-stage choroidal melanoma.”
“We are excited with the interim efficacy data of the Phase 2 study which strongly supports the assumptions for the success of the global Phase 3 trial,” said Dr. Cadmus Rich, Chief Medical Officer of Aura Biosciences. “Collectively, we believe these interim data provide strong confidence to support the launch of a global Phase 3 trial which is on track to begin enrollment this year.”
The presentation can be accessed on the Company’s website: link
Updated Safety and Efficacy Data from the Ongoing Phase 2 Trial with SC Administration
This Phase 2 trial (NCT04417530) is assessing the safety and preliminary efficacy of single- and multiple ascending-doses of bel-sar up to three cycles of treatment via SC administration for the first-line treatment of early-stage choroidal melanoma. A total of 20 adult patients have been enrolled in the trial including the single dose Cohorts 1-3 (n=6) and multiple dose escalation Cohorts 4-6 (n=14). Cohorts 5 and 6 received up to three cycles of therapy, which was considered the therapeutic regimen for evaluation. One patient in Cohort 5 (n=3) received two cycles of therapy and two patients in Cohort 5 received three cycles of therapy (40 µg/dose). All patients from Cohort 6 (n=8) were assigned to receive three cycles of therapy at the highest dose (80 µg/dose). One patient from Cohort 6, who discontinued after one cycle due to unrelated serious adverse events (SAEs), is not included. All patients in Cohorts 5 and 6 had active growth at study entry, as an enrichment strategy to evaluate preliminary efficacy. This group of patients with active growth treated at the therapeutic regimen of three cycles was evaluated for tumor growth rate, tumor control, and visual acuity preservation as the defined clinical endpoints to evaluate preliminary efficacy. The results, with an average of nine months of follow up in patients who received three cycles of therapy in Cohorts 5 and 6, and who match the criteria for the planned global Phase 3 trial, showed a
statistically significant reduction in the tumor growth rate (-0.289 mm/yr, p = <0.0001) compared to each patient’s documented growth rate at study entry, and a 100% (8/8) tumor control rate. In addition, the visual acuity preservation rate was 88% (7/8) in these cohorts, with the majority of patients being at high-risk for vision loss with tumors close to fovea or optic disk. The overall tolerability profile of bel-sar was generally favorable, with no dose-limiting toxicities, treatment-related SAEs or significant AEs reported as of January 10, 2023. There was no posterior inflammation and only mild anterior inflammation (Grade 1) in 20% of the patients. Treatment-related AEs were predominantly mild and resolved without sequalae. We believe these interim results indicate that bel-sar may offer a targeted, vision preserving therapy for the first-line treatment of primary CM, where 80% of patients are diagnosed early and have no approved therapies to date.
About Aura Biosciences
Aura Biosciences, Inc. is a clinical-stage biotechnology company developing virus-like drug conjugates (VDCs), a novel class of therapies, for the treatment of multiple oncology indications. Aura’s lead VDC candidate, belzupacap sarotalocan (bel-sar; AU-011), consists of a virus-like particle conjugated with an anti-cancer agent. Bel-sar is designed to selectively target and destroy cancer cells and activate the immune system with the potential to create long-lasting anti-tumor immunity. Bel-sar is currently in development for ocular cancers, and Aura has initiated activities for the global Phase 3 trial evaluating first-line treatment of early-stage choroidal melanoma, a vision- and life-threatening form of eye cancer where standard of care with radiotherapy leaves patients with severe comorbidities, including major vision loss. Aura plans to pursue development of bel-sar across its ocular oncology franchise including for the treatment of patients with choroidal metastasis. In addition, leveraging Aura’s technology platform, Aura is developing bel-sar more broadly across multiple cancers, including in patients with non-muscle invasive bladder cancer (NMIBC). Aura is headquartered in Boston, MA.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, and other federal securities laws. Any statements that are not statements of historical fact may be deemed to be forward looking statements. Words such as “may,” “will,” “could”, “should,” “expects,” “intends,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “projects,” “seeks,” “endeavor,” “potential,” “continue” or the negative of such words or other similar expressions that can be used to identify forward-looking statements. These forward looking statements include express or implied statements regarding Aura’s future expectations, plans and prospects, including, without limitation, statements regarding the therapeutic potential of bel-sar for the treatment of cancers including choroidal melanoma, non-muscle invasive bladder cancer and choroidal metastases; any express or implied statements regarding the Company’s expectations for the Phase 2 and Phase 3 clinical trials of bel-sar for early-stage choroidal melanoma; and Aura’s expectations regarding the estimated patient populations and related market opportunities for bel-sar.
The forward-looking statements in this press release are neither promises nor guarantees, and investors should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Aura’s control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements, including, without limitation, an improved quality of life of patients after treatment with bel-sar; a potential paradigm shift in the approach to the treatment of choroidal melanoma; the urgent need for a vision preserving targeted therapy; the potential of bel-sar compared to the existing standard of care for patients with choroidal melanoma; uncertainties inherent in clinical trials and in the availability and timing of data from ongoing clinical trials; the expected timing for submissions for regulatory approval or review
by governmental authorities; the risk that the results of Aura’s clinical trials may not be predictive of future results in connection with future clinical trials; the risk that interim data from ongoing clinical trials may not be predictive of final data from completed clinical trials; whether Aura will receive regulatory approvals to conduct trials or to market products; whether Aura’s cash resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; risks, assumptions and uncertainties regarding the impact of the continuing COVID-19 pandemic on Aura’s business, operations, strategy, goals and anticipated timelines; Aura’s ongoing and planned pre-clinical activities; and Aura’s ability to initiate, enroll, conduct or complete ongoing and planned clinical trials. These risks, uncertainties, and other factors include those risks and uncertainties described under the heading “Risk Factors” in Aura’s most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the U.S. Securities and Exchange Commission (SEC) and in subsequent filings made by Aura with the SEC, which are available on the SEC’s website at www.sec.gov. Except as required by law, Aura disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Aura’s current expectations and speak only as of the date hereof and no representations or warranties (express or implied) are made about the accuracy of any such forward-looking statements.
Investor and Media Contact:
Alex Dasalla
Head of Investor Relations and Corporate Communications
adasalla@aurabiosciences.com
Argot Partners
Matthew DeYoung
aura@argotpartners.com
Corporate Presentation February 2023 Exhibit 99.2
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", "could', "expect", "should", "plan", "intend", "estimate", "will", "potential" and "ongoing", among others, although not all forward-looking statements contain these identifying words. These forward-looking statements include statements about the initiation, timing, progress, results, and cost of our research and development programs and our current and future preclinical studies and clinical trials, including statements regarding the timing of initiation and completion of studies or trials and related preparatory work, the period during which the results of the trials will become available, and our research and development programs; our ability to successfully manufacture our drug substances and product candidates for preclinical use, for clinical trials and on a larger scale for commercial use, if approved; the ability and willingness of our third-party strategic collaborators to continue research and development activities relating to our development candidates and product candidates; our ability to obtain funding for our operations necessary to complete further development and commercialization of our product candidates; our ability to obtain and maintain regulatory approval of our product candidates; the size and growth potential of the markets for our product candidates, and our ability to serve those markets; our financial performance; the effect of the COVID-19 pandemic, including mitigation efforts and economic effects, on any of the foregoing or other aspects of our business operations, including but not limited to our preclinical studies and clinical trials and any future studies or trials; our ability to commercialize our products, if approved; and the implementation of our business model, and strategic plans for our business and product candidates. Except as otherwise noted, these forward-looking statements speak only as of the date of this presentation, and we undertake no obligation to update or revise any of such statements to reflect events or circumstances occurring after this presentation. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our most recent annual report on Form 10-K filed with the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors in our other subsequent filings with the Securities and Exchange Commission. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. We caution you not to place undue reliance on the forward-looking statements contained in this presentation. This presentation discusses product candidates that are under preclinical or clinical evaluation and that have not yet been approved for marketing by the U.S. Food and Drug Administration or any other regulatory authority. Until finalized in a clinical study report, clinical trial data presented herein remain subject to adjustment as a result of clinical site audits and other review processes. No representation is made as to the safety or effectiveness of these product candidates for the use for which such product candidates are being studied. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction.
Aura Biosciences Highlights Novel Platform to Treat Multiple Solid Tumors Developing virus-like drug conjugates (VDCs) that bind to tumor specific HSPGs* to deliver a therapeutic payload Targeting multiple solid tumor indications including ocular and bladder cancers Ocular Oncology Franchise Multi-billion-dollar addressable market opportunity Invasive standard of care that may lead to blindness and loss of eye Clinical proof of concept with two routes of administration Choroidal Melanoma: Initiated activities for the global Phase 3 trial Choroidal Metastasis: Open IND and plan to initiate Phase 2 trial 2H 2023 Urologic Oncology Franchise Durable complete responses and improved survival in in vivo bladder cancer models Synergy with checkpoint inhibitors (durable immunologic memory) Ongoing enrollment of Phase 1 trial Strong Cash Position Cash runway to fund operations into 2025 *VDCs bind to a subset of modified tumor associated glycosaminoglycans (GAGs) that are part of the heparan sulphate chain of HSPGs. Schiller et al. Viruses 2022, 14(8), 1656
Pipeline Targeting Life-Threatening Cancers with High Unmet Needs Program OTHER SOLID TUMORS OCULAR ONCOLOGY Preclinical Phase 1 Phase 2 Phase 3 Planned Milestones Choroidal Metastasis (Multiple Primary cancers with metastasis in the eye e.g. Breast and Lung) Primary Choroidal Melanoma (Suprachoroidal administration) Cancers of the Ocular Surface Non-Muscle Invasive Bladder Cancer Other HSPG* Expressing Tumors (e.g., Cutaneous Melanoma, HNSCC) 1H 2023 – FPI Phase 3 trial 2H 2023 – 12 mos. Phase 2 data 2H 2023 – Initiate Phase 2 trial 2024 – Phase 2 data 2H 2023 – Phase 1 data Global Commercial Rights for All Product Candidate Indications *VDCs bind to a subset of modified tumor associated glycosaminoglycans (GAGs) that are part of the heparan sulphate chain of HSPGs. Schiller et al. Viruses 2022, 14(8), 1656
Targeted Oncology Platform: Virus-Like Drug Conjugates (VDCs) Virus-Like Particle Conjugated to a Cytotoxic Payload Selective Binding to Tumor Associated HSPGs* Virus-Like Particle (VLP) Virus-Like Drug Conjugate (VDC) Cx Cytotoxic Drug Kines et al; International Journal of Cancer, 138;901–911, February 2016; Kines et al; Molecular Cancer Therapeutics, 17(2) February 2018; Kines et al; Cancer Immunology Research, May 2021 Potential Key Differentiation: Potency, Multivalent Binding and Selectivity Potential Treatment of Multiple Solid Tumors *VDCs bind to a subset of modified tumor associated glycosaminoglycans (GAGs) that are part of the heparan sulphate chain of HSPGs. Schiller et al. Viruses 2022, 14(8), 1656
Bel-sar is a VDC with a Novel Dual Mechanism of Action Light Activatable Drug Bel-sar Bel-sar is a novel VDC that consists of VLP conjugated to ~200 molecules of light activatable drug Potential Key Differentiation: Agnostic to Genetic Mutations, Less Susceptible to Resistance Mechanisms, Long Term Anti-tumor Immunity Kines et al; Cancer Immunology Research, May 2021 VDCs bind to a subset of modified tumor associated glycosaminoglycans (GAG) that are part of the heparan sulphate chain of HSPGs. Schiller et al. Viruses 2022, 14(8), 1656 Bel-sar – Belzupacap Sarotalocan Reactive oxygen species disrupts cell membrane and organelles
Ocular Oncology Franchise Bel-sar INN: belzupacap sarotalocan Target Indications: Early-Stage Choroidal Melanoma Choroidal Metastasis Other Ocular Cancers
Primary Choroidal Melanoma – High Unmet Medical Need with No Drugs Approved Choroidal Melanoma is a Rare and Life-Threatening Ocular Cancer Kaliki et al; Eye (Lond) 2017 Feb; 31(2): 241–257; Clearview & Putnam & Assoc. Market Research; Source: Peddada. J Contemp Brachytherapy. August 2019 Most common primary intraocular cancer in adults Impacts 11,000 patients in US/Europe per year ~80% patients diagnosed with early-stage disease Melanoma cells Melanocytic Lesion Benign nevus cells Standard of Care is Radiotherapy or Enucleation Blindness, Eye Loss, and Disfiguration The choroid is the part of the uvea that is behind the retina
Bel-sar has the Potential to be the First Approved Therapy in Primary Choroidal Melanoma No radioactive co-morbidities Preservation of vision Local tumor control Opportunity to treat early and reduce risk of metastases Improvement in safety and quality of life intravitreal suprachoroidal Bel-sar is Delivered by Simple Intravitreal or Suprachoroidal Injection Goals of Treatment Light Activation with Standard Ophthalmic Laser Bel-sar – Belzupacap Sarotalocan
Ocular Oncology Franchise Represents a Multi-Billion Dollar Addressable Market Opportunity Ocular Oncology Franchise total addressable market ~80% of patients are diagnosed at the early stage (indeterminate lesions (ILs) and small tumors) Current radiotherapy treatment Leaves ~70% of patients with major irreversible vision loss within 5-10 years ~100 Ocular Oncologists in US/EU — focused call point <20 Field Based Team Intend to add small sales force to launch globally 33,500 ClearView & Putnam & Assoc. Epidemiology Analysis Choroidal Melanoma and Choroidal Metastasis American Cancer Society- Retinoblastoma statistics Batsi et al Cornea 2003 Ocular Surface squamous neoplasia: a review Multibillion $ addressable market opportunity Cancers of the Ocular Surface Retinoblastoma Choroidal Melanoma Choroidal Metastasis 11,000 patients/year 20,000 patients/year 500 patients/year 2,000 patients/year 11,000 Choroidal Melanoma patients diagnosed each year (US/EU) Initial Indication Follow-on Indication
No Drugs Approved and No Known Competition in Early-Stage Disease Plaque Brachytherapy Proton Beam Plaque Brachytherapy Proton Beam Watch & Wait Chemotherapy Enucleation 80% ~ 9000 patients Diagnosed with Early-Stage Disease: Indeterminate Lesions and Small Melanomas CM – Choroidal Melanoma Initial Path to Market Aura’s Bel-Sar in Phase 3 development as the potential to be the first approved first line treatment in Primary Choroidal Melanoma Ideaya’s Darovasertib Phase 2 development for Metastatic and (Neo)/adjuvant Uveal Melanoma Immunocore’s Kimmtrack approved to treat patients with Metastatic Uveal Melanoma Aura’s Bel-Sar has the potential to expand into medium 11,000 patients with Choroidal Melanoma diagnosed each year in US/EU Medium Large Metastatic
Goal for Bel-sar: Eliminate Malignant Cells in the Choroid and Preserve Vision Endpoint Endpoint Definitions Tumor Progression Growth in Tumor Height ≥0.5mm or ≥1.5 mm in Largest Basal Diameter (LBD) Visual Acuity Failure Decrease from baseline: ≥15 letters Tumor Thickness Growth Rate Change in tumor height over time Bel-sar – Belzupacap Sarotalocan Key Endpoints Aligned with Clinical Practice and FDA Objective of Treatment is to Obtain a Local Cure with Visual Acuity Preservation Similar to Current Clinical Practice with Radiotherapy - Local Tumor Control is Equivalent to a Local Cure
Ph 2 Trial - Evaluating Suprachoroidal Administration to Determine Optimal Administration Route Ph2 SC Trial Design *2 subjects were planned; third subject was additionally enrolled due to dose error in 1 subject ClinicalTrials.gov Identifier: NCT04417530 ; AU-011-202 Goal: To Determine Safety, Optimal Dose and Therapeutic Regimen with Suprachoroidal Administration SC – Suprachoroidal; LBD – Largest Basal Diameter One Cycle = Doses on days 1, 8, and 15 1 dose- 20 μg x 1 Laser 1 dose- 40 μg x 1 Laser 1 dose- 40 μg x 2 Lasers 2 doses- 40 μg x 2 Lasers QWx2 Cohort 1 (n=1) Cohort 2 (n=3*) Cohort 3 (n=2) Cohort 4 (n=3) Cohort 5 9 doses- 80 μg x 2 Lasers QWx3 3 cycles Cohort 6 (n=up to 10) ONGOING 2 Cycles (n=1) 3 Cycles (n=2) 6-9 doses- 40 μg x 2 Lasers QWx3 Up to 3 cycles 1- 2 Doses (n=9) (Sub-Therapeutic Regimen) 6 Doses 2 Cycles (n=1) 9 Doses 3 Cycles (Therapeutic Regimen) n=9 Enrollment Criteria Representative of Early-Stage Disease: Indeterminate lesions and small choroidal melanomas Enrichment Strategy with active growth: Tumor thickness ≥0.5 mm and ≤2.5 mm LBD ≤10 mm Active tumor growth (≥0.3mm) within 2 years of screening Same criteria as the planned Phase 3
Ph 2 Interim Tumor Control Rates Demonstrated a Dose Response Tumor Progression: change from baseline in thickness ≥0.5mm; or in LBD ≥1.5mm confirmed by at least one repeat assessment Interim Data- January 10, 2023 Populations Total Patients (n) Tumor Control Rate Average Follow-up (months) All Doses/Regimens All Treated Patients 20 55% (11/20) 9 Lower Doses/Regimens Up to 2 Cycles (20µg-40µg) 10 20% (2/10) 10 Highest Doses/Regimens*+ 3 Cycles (n=9) 40µg (n=2)/80µg (n=7) 9 89% (8/9) 8 Average 8-10 Months of Follow Up *One subject in C6 who discontinued after 1 cycle due to unrelated SAEs is not included +Assigned regimen of 3 cycles (Cohort 6) and Cohort 5 subjects who received 3 cycles, each cycle comprised of 3 once/week treatments of 40µg x 2 Laser or 80µg x 2 Laser Lower dose regimens (n=10) include cohorts 1-4 and 1 patient in Cohort 5 that received 2 cycles Dose Response Observed with Interim Tumor Control Rates Demonstrated Meaningful Clinical Benefit Dose Response: Lower Regimens vs. 3 Cycle Regimens LBD – Largest Basal Diameter Up to 2 cycles regimens (n=10) 3 cycle regimens (n=9) 89% 20%
Ph 2 Interim Analysis Demonstrated Tumor Control Rate 89%-100% Ph 2 Interim Analysis Demonstrated Tumor Control Rate of 100% in Planned Ph 3 Population^ Tumor Progression: change from baseline in thickness ≥0.5mm; or in LBD ≥1.5mm confirmed by at least one repeat assessment; Interim Data- January 10, 2023; post-SOC data not included Progression Definition based on Tumor Thickness (Increase ≥0.5mm) Subject 015-2029 had circumpapillary tumor – similar subjects will be excluded from Phase 3 trial 89%-100% Tumor Control Rate: Active Growth and Therapeutic Regimen (3 cycles) Change from Baseline in Tumor Thickness Over 12 Months Treatment Timeframe Follow-up Timeframe Change from Baseline in Tumor Thickness (mm) Bel-sar – Belzupacap Sarotalocan Bel-sar treatment cycles Populations Total Patients (n) Tumor Control Rate Average Follow-up (months) Highest Doses/Regimens 3 Cycles (n=9) 40µg (n=2)/80µg (n=7) 9 89% (8/9) 8 Highest Doses/Regimens - Planned Phase 3^ 3 Cycles (n=8) 40µg (n=2)/80µg (n=6) 8 100% (8/8) 9 Average 8-9 Months of Follow Up One subject in C6 who discontinued after 1 cycle due to unrelated SAEs is not included Assigned regimen of 3 cycles (Cohort 6) and Cohort 5 subjects who received 3 cycles, each cycle comprised of 3 once/week treatments of 40µg x 2 Laser or 80µg x 2 Laser ^ One subject in C6 with circumpapillary tumor not included (similar subjects not planned in Phase 3 trial)
Ph 2 Interim Analysis Demonstrated Visual Acuity Preservation ~90% Interim Data Demonstrated High Vision Preservation Rates Across All Groups Including Patients at High Risk for Vision Loss SC – Suprachoroidal Populations Total Patients (n) Vision Failures (n) Vision Preservation Rate Mean Change from Baseline at Last Visit (letters) Average Follow-up (months) All Dose Cohorts All Treated Patients 20 2 90% -3.7 9 Lower Doses/Regimens Up to 2 cycles (20µg-40µg) 10 1 90% -3.2 10 Highest Doses/Regimens*+ 3 Cycles (40µg-80µg) 40µg (n=2)/80µg (n=7) 9 1 89% -4.8 8 Highest Doses/Regimens - Planned Phase 3*+ 3 Cycles (40µg-80µg)^ 40µg (n=2)/80µg (n=6) 8 1 88% -5.3 9 Vision Preservation Rates *One subject in C6 who discontinued after 1 cycle due to unrelated SAEs is not included +Assigned regimen of 3 cycles (Cohort 6) and Cohort 5 subjects who received 3 cycles, each cycle comprised of 3 once/week treatments of 40µg x 2 Laser or 80µg x 2 Laser Vision Failure confirmed loss ≥15 letters at ≥Week 39; post-SOC data not included ^7 out of 8 subjects in this subgroup were high-risk for vision loss (tumor edge ≤ 3 mm from the foveola or optic disc) Interim Data- January 10, 2023
Ph 2 Interim Data Demonstrated Statistically Significant Tumor Growth Rate Reduction Interim Data Showed Growth Arrest in Planned Phase 3 Population with a p-value of <0.0001 p=0.0001 p= <0.0001 Statistically Significant Change in Tumor Growth Rate (mm/yr): Therapeutic Regimen (3 cycles) Bel-sar – Belzupacap Sarotalocan Planned Phase 3 Historical Growth Rate (mm/yr) Excludes subject with circumpapillary tumor Bel-sar Growth Rate (mm/yr) n Historical Growth Rate (mm/yr) AU-011 Growth Rate (mm/yr) Growth Rate Reduction (mm/yr) p-value Average Follow up (months) Highest Doses/Regimens 3 Cycles (40µg-80µg) 40µg (n=2)/80µg (n=7) 9 0.454 0.169 -0.285 0.0001 8 Highest Doses/Regimens - Planned Phase 3^ 3 Cycles (40µg-80µg) 40µg (n=2)/80µg (n=6) 8 0.382 0.093 -0.289 <0.0001 9 Tumor thickness growth rates/ slopes estimated using MMRM (random intercept and slope model for Hx and Study periods) Change in Tumor Growth After Treatment with Bel-sar One subject in C6 who discontinued after 1 cycle due to unrelated SAEs is not included Assigned regimen of 3 cycles (Cohort 6) and Cohort 5 subjects who received 3 cycles, each cycle comprised of 3 once/week treatments of 40µg x 2 Laser or 80µg x 2 Laser ^One subject in C6 with circumpapillary tumor not included (similar subjects not planned in Phase 3 trial)
Ph 2 Ongoing Tolerability Evaluation Continues to Be Favorable No Grade 3 AEs and Majority of AEs Were Transient and Resolved Without Clinical Sequelae Tolerability Profile Supports Indication as a First Line Treatment in Early-Stage Disease *J. Contemp Brachytherapy. J. 2019 Aug; 11(4): 392–397.; Arch Ophthalmol. 2000;118(9):1219-1228; Curr. Opin. Ophthalmol. 2019 May;30(3):206-214; Eye 2017 Feb;31(2):241-257 **High-Risk Subjects are those with tumors <3mm to fovea or optic nerve Adverse Event Radiotherapy* Bel-Sar+ Surgeries secondary to AEs+ (e.g., Cataracts) 40%+ 0% Radiation Retinopathy 40%+ 0% Neovascular Glaucoma 10% 0% Dry Eye Syndrome 20% 0% Strabismus 2%+ 0% Retinal Detachment 1-2% 0% Vision Loss (≥15 letters) ~70% ~10% Serious Adverse Event Radiotherapy* Bel-Sar+ Scleral Necrosis 0-5% 0% Enucleation/Eye Loss 10-15% 0% Vision Loss in High-Risk Subjects** (≥30 letters) ~90% 0%++ *Cross-trial comparison of Radiotherapy and AU-011-202 +Related to bel-sar or laser ++75% (15/20) of patients in Ph2 SC trial were at high risk for vision loss Bel-Sar – Belzupacap Sarotalocan Table presents percentage of subjects with AEs related to bel-sar or laser by severity and overall; subjects with more than 1 AE are counted in the highest severity group Interim Data- January 10, 2023 Ongoing Phase 2 Safety Outcomes with SC Administration All Treated Subjects (n=20) Drug/Laser Related Adverse Events ≥10% Subjects Grade I Grade II Grade III Total Anterior Chamber Cell/ Inflammation 25% 0 0 25% Conjunctival Hyperemia 15% 0 0 15% Eye Pain 10% 5% 0 15% Punctate Keratitis 10% 0 0 10%
Cohort 5 Subject with Documented Tumor Growth Tumor location: Superotemporal Photograph and ultrasound at baseline TT: 1.50 mm, LBD: 8.92 mm (IRC reads) Photograph and ultrasound at 12 months TT: 1.47 mm, LBD: 8.55 mm (IRC reads) Baseline Week 4 Week 8 Week 12 Week 26 Week 39 Week 52 BCVA (letter score) 91 92 92 89 89 90 89 Durable Response to Treatment with Tumor Control & Vision Preservation at 1 Year, with 3 Cycles BCVA: best corrected visual acuity; IRC: independent reading center; LBD: largest basal diameter; TT: tumor thickness; AU-011= Bel-sar Historical and projected growth based on MMRM
Randomized Controlled Global Phase 3 Trial
Global Phase 3 Trial Design Using Suprachoroidal Administration Fast Track and Orphan Designations Time to Tumor Progression Tumor Growth Rate over 52 weeks Composite time to event analysis: Tumor progression or visual acuity failure between Intervention Group (High Dose) and Sham Group Primary Endpoint Key Secondary Endpoints Adaptive Design with Conservative Assumptions Optimizes Probability of Success Bel-Sar – Belzupacap Sarotalocan; LSLV- last subject last visit n=8 n=4 n=8 12 Mos Primary Endpoint Enrollment (n=85) Potential to enroll additional n =20 (total n=105) Randomize (2:1:2) 80 µg bel-sar treatment arm (n=34) 40 µg bel-sar treatment arm (n=17) Sham control arm (n=34) Interim Analysis 12 Mos Primary Endpoint
Clinical Endpoints to Support Approval in Alignment with Regulatory Agencies Note: Tumor Height (TH) is synonymous with Tumor Thickness; VA – Visual Acuity; Bel-sar – Belzupacap Sarotalocan Composite Endpoint Conservative Assumptions Provide >90% Power to Maximize Probability of Success with Single Global Phase 3 Trial Endpoint Endpoint Assumptions Endpoint Definitions Tumor Progression Bel-sar: 35% Tumor Progression Sham: 85% Tumor Progression Growth in Tumor Height ≥0.5mm or ≥1.5 mm in Largest Basal Diameter Vision Acuity Failure Bel-sar: 15% VA Failure Sham: 2% VA Failure Decrease from baseline: ≥15 letters Tumor Thickness Growth Rate Bel-sar vs Sham : -0.28mm/year reduction Change in tumor height over time
Choroidal Metastasis
Ocular Oncology Franchise Represents a Multi-Billion Dollar Addressable Market Opportunity Ocular Oncology Franchise total addressable market Same Call Point as CM ~100 Ocular Oncologists in US/EU — focused call point Same Field Force as CM <20 Field Based Team Intend to add small sales force to launch globally 33,500 ClearView & Putnam & Assoc. Epidemiology Analysis Choroidal Melanoma and Choroidal Metastasis American Cancer Society- Retinoblastoma statistics Batsi et al Cornea 2003 Ocular Surface squamous neoplasia: a review Multibillion $ addressable market opportunity Cancers of the Ocular Surface Retinoblastoma Choroidal Melanoma Choroidal Metastasis 11,000 patients/year 20,000 patients/year 500 patients/year 2,000 patients/year 20,000 Choroidal Metastasis patients diagnosed each year (US/EU) 2x Doubles the market opportunity Initial Indication Follow-on Indication
Choroidal Metastasis is a High Unmet Medical Need Choroidal Metastasis Cause Decreased Vision and Decreased Quality of Life in Patients Fighting Metastatic Cancer Originate from Multiple Primary Cancers (e.g. Breast and Lung) 20,000/year eyes diagnosed in US 88% with choroidal location 72% unilateral and solitary Standard of Care is Radiotherapy Blindness, Eye Loss, and Disfiguration Breast 40-53% Lung 20-29% GI 4% Kidney 2% Prostate 2% Skin 2% Mathis et al. New concepts in choroidal metastasis, Progress in retinal and eye research (2019), Cohen, Ocular metastasis, Eye (2014), Shields et al. Survey of 520 eyes with uveal metastases. Ophthalmology (1997), Namad et al. Bilateral choroidal metastasis from non-small lung cancer, Case reports in oncological medicine (2014).
Tumor Regression Prolonged Survival Breast Cancer In-Vivo (Syngeneic Mouse Model, EMT-6) Tumor cells were implanted subcutaneously. AU-011 treatment was initiated when tumors reached approximately 50 mm3. Treatment consisted of a single intravenous administration of AU-011 followed 12 hours later by light activation (400 mW/cm2, 58 J/cm2). Tumor volumes were measured over time (N=8-12) Bel-sar has Demonstrated Dose-Dependent Activity for Cancer Types Known to Metastasize to the Choroid Single Administration of Bel-sar Showed Tumor Regression and Prolonged Survival in a Dose-Dependent Fashion Data Supportive of Moving into Phase 2 Trial 2H 2023 Savinainen et al., ARVO 2022 Abstract # 3709397; AU-011 – Bel-sar – Belzupacap Sarotalocan
Urologic Oncology Bel-sar INN: belzupacap sarotalocan Target Indications: Non-Muscle Invasive Bladder Cancer
Bel-Sar is a Clinical Asset with a Multibillion Dollar Market Opportunity in Non-Muscle Invasive Bladder Cancer NMIBC is High Unmet Need High Incidence globally >500,000 patients/year Rate of recurrence is high Bel-Sar’s MoA Well Suited to NMIBC Strong precedent for immune-activators in NMIBC (BCG) Bladder tumors physically accessible via cystoscope (injection, laser) Robust Nonclinical Data Package Durable CRs and improved survival in in vivo bladder cancer models Synergy with checkpoint inhibitors (durable immunologic memory) Read Through from Ocular Clinical Proof of Concept Two clinical trials demonstrate robust efficacy in Ocular Oncology Initiating global Ph 3 study in choroidal melanoma Phase 1 Study Ongoing Initial data available in 2H 2023 CR – complete responses; BCG - Bacillus Calmette–Guérin
NMIBC is a High Unmet Need with High Recurrence Rate Mechanism of Action Supports Bel-sar Opportunity as Potential Front-Line Treatment Following Initial Diagnosis and/or BCG Refractory Disease Source: Putnam Associates Primary Research & Literature Review, July 2021; NMIBC – Non-Muscle Invasive Bladder Cancer; TURBT - trans urethral resection of bladder tumor; BCG - Bacillus Calmette–Guérin; Bel-sar – Belzupacap Sarotalocan NMIBC Cross section of the bladder wall and staging of bladder cancer 573,000 New cases NMIBC/year globally 81,000 New cases/year in the US Problem Treatment Guidelines Risk Stratification Progression with no alternative option but Cystectomy Mix of Chemo / BCG High Risk (30%) Mix of TURBT + Chemo / BCG Failure of BCG/Chemo ~40% Intermediate Risk (30%) Surveillance or TURBT + Chemo Recurrence after TURBT Low Risk (40%)
Durable CRs with Single Administration of Bel-sar in Bladder Cancer Model Data Demonstrate Robust Nonclinical Activity Supporting Development of Bel-sar as Single Agent and in Combination with Checkpoint Inhibitors Syngeneic Mouse Tumor Bladder Model (MB49 Model in C57BL/6 Mice) (N=8 -10/group) Tumor Regression Survival Survival After Re-challenge AU-011 Single Dose Treatment of Tumor Caused Anti-Tumor Immune Response and Prevented Tumor Growth After Re-Challenge Bel-sar: Belzupacap Sarotalocan; CR: Complete Responses Kines et al. Can Immunol Res 9(6):693-706, 2021
Novel Approach using Intra-mural Administration Ongoing Phase 1 Trial Designed to Establish Safety, and Optimize Administration in Intermediate and High Risk NMIBC Patients Intra-mural Administration Bel-sar, AU-011 – Belzupacap Sarotalocan Distribution Into the Mucosal Layer Into the Bladder Wall Bel-sar will be administered in the lamina propria close to the base of the tumor 3 Hour Post AU-011 Injection (Dog tox study): Bel-Sar positive staining (pink) extends laterally at the junction between the submucosa and superficial muscularis of the bladder
Ongoing Ph 1 Trial Evaluating Bel-sar Distribution, Local Necrosis and Evidence of Immune Activation Bel-sar, AU-011 – Belzupacap Sarotalocan Without Light With Light
Strategy & Key Milestones
Aura Biosciences Investment Highlights Technology Platform Clinical Data Highlights 2023 Milestones Key Highlights Virus-like Drug Conjugates Novel class of cancer therapies - tumor specific cytotoxicity combined with immune activation Targeting multiple solid tumor indications initially focusing on ocular and urologic cancers Ocular Oncology Franchise: Positive data in completed Phase 1b/2 trial (IVT) Positive interim data in ongoing Phase 2 trial (SC) Initiated activities for the global Phase 3 trial Urologic Oncology Franchise: Enrolling patients in Phase 1 trial in NMIBC Primary Choroidal Melanoma: 1H 2023: Dose first patient in global Phase 3 trial 2H 2023: Phase 2 SC Data Choroidal Metastasis: 2H 2023: Initiate activities for Phase 2 trial Non-Muscle Invasive Bladder Cancer: 2H 2023: Interim Phase 1 data Strong Phase 2 Clinical Proof of Concept Phase 3 Ready Clinical Asset Multi-Billion Dollar Market Opportunity Strong Cash Position
Appendix: Phase 1b/2 IVT Trial
Phase 1b/2 IVT – Key Patient Populations and Objectives Enrichment Strategy to Enroll Subjects with Actively Growing Tumors Provides Important Insight into How Bel-sar May Perform in Phase 3 Trial Primary Objective: Safety Drug or treatment related adverse events (AEs) / serious adverse events (SAEs) Secondary Objective: Efficacy Tumor thickness growth rate before and after treatment Local tumor control Visual acuity preservation All Patients Enrolled with Clinical Diagnosis of Choroidal Melanoma or Indeterminate Lesions All Treated Patients Patients Treated with 2 Cycles Safety Evaluation (All Treated) Efficacy Evaluation Therapeutic Regimen (2 Cycles) Patients with Active Growth Treated with 2 Cycles n=56 n=20 Bel-sar – Belzupacap Sarotalocan
Phase 1b/2 – Demonstrated Favorable Tolerability Profile Majority of AEs Were Transient and Resolved Without Clinical Sequelae Tolerability Profile Supports Indication as a First Line Treatment in Early-Stage Disease *J. Contemp Brachytherapy. J. 2019 Aug; 11(4): 392–397.; Arch Ophthalmol. 2000;118(9):1219-1228; Curr. Opin. Ophthalmol. 2019 May;30(3):206-214; Eye 2017 Feb;31(2):241-257 **High-Risk Subjects are those with tumors <3mm to fovea or optic nerve AU-011 Treatment Related AEs ≥15% Subjects (n=56) Final Grade I/II Grade III Vitreous Inflammation 83.9% 7.1% Anterior Chamber Inflammation 67.9% 3.6% Increase in Intraocular Pressure 46.4% 0 Pigmentary Changes/Peritumoral 37.5% 0 Keratic Precipitates 23.2% 0 Floaters/Vitreous Opacity 19.7% 1.8% Decreased visual acuity 19.6% 1.8% Treatment Related SAEs (n=56) Vision Loss (juxtafoveal tumor, n=2) 3.6% SAE of vision loss in two subjects with tumors close to fovea due to pigmentary changes at the edge of the tumor SAEs are listed separately in the SAE table Completed Ph 1b/2 IVT trial (AU-011-101) Adverse Event Radiotherapy* Bel-Sar Surgeries secondary to AEs (e.g., Cataracts) 40%+ ~13% Radiation Retinopathy 40%+ 0% Neovascular Glaucoma 10% 0% Dry Eye Syndrome 20% ~2% Strabismus 2%+ 0% Retinal Detachment 1-2% ~2% Vision Loss (≥15 letters) ~70% ~21% Serious Adverse Event Radiotherapy* Bel-Sar Scleral Necrosis 0-5% 0% Enucleation/Eye Loss 10-15% 0% Vision Loss in High-Risk Subjects** (≥30 letters) ~90% 4.6%+ Cross-trial comparison of AU-011-101 and Radiotherapy +77% (43/56) of patients in Ph1b/2 IVT trial were at high risk for vision loss ; 2/43= 4.6% Bel-Sar – Belzupacap Sarotalocan
Phase 1b/2 IVT- 70% Tumor Control Rate and Statistically Significant Growth Rate Reduction Positive Data in Two Efficacy Endpoints in Patients with Early-Stage Choroidal Melanoma Cohorts 1-9 include single dose escalation cohorts and multiple dose escalation cohorts up to 1 cycle of treatment; Cohorts 10-12 include 2 cycles of treatment at the highest dose Lower Doses/Regimens Highest/Therapeutic Dose/ Regimen p=0.018, n=14 Tumor Control Rates at 12 months Change in Tumor Growth Rate Historical Growth Rate (mm/yr) Bel-sar Growth Rate (mm/yr) Disease-modifying effect supports tumor is inactive and malignant cells have been targeted by bel-sar Completed Ph1b/2 IVT trial (AU-011-101) Bel-sar – Belzupacap Sarotalocan 0.555 0.072
Phase 1b/2 – 64% Patients with Active Growth Achieved Tumor Control when Treated with Therapeutic Regimen We Believe Results Support Bel-sar as First Line Treatment to Help Many Patients Avoid the Need for Radiotherapy Change from Baseline in Tumor Thickness Over 12 Months Completed Ph1b/2 IVT trial (AU-011-101) Progression Definition Tumor Height Increase >0.5mm Populations Total Patients (n) Tumor Control Rate (at 12 months) Therapeutic Dose/Regimen (2 Cycles) All Patients Treated with 2 Cycles 20 70% (14/20) All Patients with Active Growth Treated with 2 Cycles 14 64% (9/14) Tumor control failure (progression): Growth from baseline in Tumor Height >0.5mm or LBD >1.0mm due to definitive Tumor Growth (ie, not judged by the Investigator to be due to inflammation/swelling, hemorrhage or pigmentary changes) and not treated with standard of care Tumor Control Rate at 12 months All Patients with Active Growth Treated with 2 Cycles (n=14) Bel-sar – Belzupacap Sarotalocan
Visual Acuity was Preserved in Majority of Patients with IVT Administration of Bel-sar Vision was Preserved in Majority of Patients Whereas Radiotherapy Often Leads to Irreversible and Long-Term Severe Vision Loss Populations Total Patients (n) Vision Preservation Rate Failure: Long-term loss ≥15 letters All Dose Cohorts All Treated Patients 56 86% (48/56) Patients with Active Growth - High Risk for Vision Loss 17 76% (13/17) Therapeutic Regimen (2 cycles) All Treated Patients 20 75% (15/20) Patients with Active Growth 14 71% (10/14) Vision Preservation Rates Phase 1b/2 IVT Study Follow up 12 months 1 patient had loss ≥15 letters at Week 52 visit which recovered within 15 letters at the next visit which was ~3 weeks after standard of care (SOC); all other post-SOC data excluded for all subjects Completed Ph1b/2 IVT trial (AU-011-101) Bel-sar Subjects Mean (±95%CI) Change from Baseline in logMAR scores Over 2 Years rMCC Study Matched Plaque Patients Mean (±95%CI) Change from Baseline in logMAR Score Over 5 Years rMCC Study Retrospective Match Case Control Study (rMCC) to evaluate visual acuity outcomes of bel-sar vs radiotherapy. Matching performed by independent statistician.. 43 bel-sar patients with HRVL were matched to 150 radiotherapy patients. Bel-sar – Belzupacap Sarotalocan