false 0001501796 0001501796 2022-06-19 2022-06-19





Washington, D.C. 20549







Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of Earliest Event Reported): June 19, 2022



Aura Biosciences, Inc.

(Exact name of registrant as specified in its charter)




Delaware   001-40971   32-0271970

(State or other jurisdiction

of incorporation)



File Number)


(I.R.S. Employer

Identification No.)


85 Bolton Street

Cambridge, Massachusetts

(Address of principal executive offices)   (Zip Code)

Registrant’s telephone number, including area code (617) 500-8864

Not Applicable

(Former name or former address, if changed since last report)



Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:


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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.

Securities registered pursuant to Section 12(b) of the Act:


Title of each class





Name of each exchange

on which registered

Common Stock, $0.00001 par value per share   AURA   The Nasdaq Global Market




Item 7.01 Regulation FD Disclosure.

On June 22, 2022, Aura Biosciences, Inc. (the “Company”) issued a press release titled “Aura Biosciences Reports Topline Data from a Retrospective Study of Belzupacap Sarotalocan (AU-011) versus Radiotherapy Supporting the Value of a Vision Preserving Therapy for the Treatment of Patients with Early-Stage Choroidal Melanoma.” The Company presented the data at the 20th congress of the International Society of Ocular Oncology on June 19, 2022. A copy of the press release and a copy of the presentation are attached as Exhibits 99.1 and 99.2, respectively, to this Current Report on Form 8-K and are incorporated herein by reference.

The information furnished under this Item 7.01, including Exhibits 99.1 and 99.2, 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 9.01. Financial Statements and Exhibits.

(d) Exhibits.




99.1    Press Release issued by the Company, dated June 22, 2022, furnished herewith.
99.2    Aura Biosciences, Inc. 2022 ISOO Presentation, dated June 19, 2022, furnished herewith.
104    Cover Page Interactive Data (embedded within the Inline XBRL document)


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: June 22, 2022     AURA BIOSCIENCES, INC.

/s/ Elisabet de los Pinos

      Elisabet de los Pinos, Ph.D.
      President and Chief Executive Officer

Exhibit 99.1



Aura Biosciences Reports Topline Data from a Retrospective Study of Belzupacap Sarotalocan (AU-011) versus Plaque Radiotherapy Supporting the Value of a Vision Preserving Therapy for the Treatment of Patients with Early-Stage Choroidal Melanoma

In this Retrospective Matched Case Control Study, Belzupacap Sarotalocan Achieved Statistically Significant Vision Preservation Compared to Plaque Radiotherapy, the Current Standard of Care

CAMBRIDGE, MA – June 22, 2022 – Aura Biosciences Inc. (NASDAQ: AURA), a clinical-stage biotechnology company developing a novel class of virus-like drug conjugate (VDC) therapies for multiple oncology indications, reported results from a retrospective, matched case control study. This retrospective analysis assessed the visual acuity of patients following treatment with plaque radiotherapy compared with prospective data on visual acuity in subjects with early-stage choroidal melanoma treated with belzupacap sarotalocan by intravitreal administration in the Phase 1b/2 trial (NCT03052127).

“These results point to the high unmet medical need for a first line vision preserving therapy for the treatment of early-stage choroidal melanoma given the high levels of irreversible visual acuity loss with the current standard of care with radiotherapy,” said Carol Shields, MD, Chief of the Ocular Oncology Service at Wills Eye Hospital and Professor of Ophthalmology at Thomas Jefferson University. “Being able to treat the disease early, avoid radiotherapy and spare long-term vision loss in many patients, as well as potentially reducing the risk of metastatic disease, could represent a paradigm shift in our approach to the treatment of choroidal melanoma. This would be a significant improvement in the quality of life for patients with this life-threatening rare disease.”

Results from the Retrospective Study

Study Design

This retrospective, matched case control study compared visual acuity outcomes for 43 patients from Aura’s Phase 1b/2 trial evaluating intravitreal administration of belzupacap sarotalocan in patients with early-stage choroidal melanoma (AU-011-101, NCT03052127) to 150 patients from the subject database of a previously completed and published study where patients with small choroidal melanoma had been treated with plaque radiotherapy (Shields, et al. “Visual Outcome and Millimeter Incremental Risk of Metastasis in 1780 Patients With Small Choroidal Melanoma Managed by Plaque Radiotherapy.” JAMA Ophthalmology. September 27, 2018). Both cohorts of patients were at high risk for vision loss due to having the tumor edge within 3.0 mm of the fovea. The patients were matched for tumor height, tumor diameter, distance from the fovea and baseline visual acuity, which are among the core factors that impact visual acuity after treatment.




Key Findings:



The vision results of patients with early-stage choroidal melanoma treated with radiotherapy showed the long term, progressive and irreversible loss of visual acuity in patients where tumors were close to the fovea.



The loss of vision in radiotherapy patients was ≥3 lines in a majority of patients as early as 2 years and ≥6 lines as early as 3 years.



We believe the comparison of the belzupacap sarotalocan and radiotherapy results supports the potential benefit of a targeted treatment achieving a statistically significant difference in visual acuity preservation as soon as two years including for both logMAR (Logarithm of the Minimum Angle of Resolution) vision (p = 0.0094) and change in logMAR vision (p = 0.0323).



We believe the progressive loss of visual acuity with radiotherapy observed in this retrospective study underscores the urgent need for a vision preserving targeted therapy.



The findings of this retrospective study were consistent with published clinical data supporting the irreversible loss of visual acuity after treatment with radiotherapy.

“We are committed to developing the first potential targeted therapy for patients with early-stage choroidal melanoma. We believe the visual acuity results of the retrospective matched case control study are exciting because they support the high unmet medical need for a long-term vision preserving therapy,” said Dr. Cadmus Rich, Chief Medical Officer and Head of R&D of Aura Biosciences. “Belzupacap sarotalocan is currently being evaluated in a Phase 2 dose escalation clinical trial (AU-011-202, NCT04417530) using suprachoroidal administration in patients with early-stage choroidal melanoma. We remain on track to initiate our pivotal trial by the end of 2022.”

Study Limitations include the retrospective nature and utilizing a matched case control design. The mean follow-up for patients treated with belzupacap sarotalocan in this initial analysis was 15.6 months. Due to the retrospective nature of this analysis, it is hypothesis-generating; no formal conclusions can be drawn. Aura has also initiated a prospective matched case control study to further evaluate the long-term visual acuity results of belzupacap sarotalocan from the Phase 2 trial AU-011-202 using suprachoroidal administration versus radiotherapy.




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, AU-011 (belzupacap sarotalocan), consists of a virus-like particle conjugated with an anti-cancer agent. Belzupacap sarotalocan selectively targets and destroys cancer cells and activates the immune system with the potential to create long-lasting anti-tumor immunity. Belzupacap sarotalocan is currently in development for ocular cancers, with an ongoing Phase 2 dose escalation clinical trial evaluating first-line treatment of 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 belzupacap sarotalocan across its ocular oncology franchise including for the treatment of patients with choroidal metastases. In addition, leveraging Aura’s technology platform, Aura is developing belzupacap sarotalocan more broadly across multiple cancers, starting with a planned Phase 1 clinical trial in patients with non-muscle invasive bladder cancer (NMIBC). Aura is headquartered in Cambridge, MA.

For more information, visit aurabiosciences.com, or follow us on Twitter and LinkedIn.

Forward Looking Statement

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 belzupacap sarotalocan for the treatment of cancers including choroidal melanoma and NMIBC and expectations with respect to the clinical development of belzupacap sarotalocan.




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 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 Aura’s clinical trials may not be predictive of future results in connection with future 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:

Matthew DeYoung

Argot Partners

212-600-1902 | aura@argotpartners.com




Slide 1

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 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. 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.

Slide 3

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 Martine Jager, MD, PhD Professor of Ophthalmology Leiden University

Slide 4

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 design Oncology Pipeline Solid tumor development programs Platform to develop additional VDCs Anticipated Milestones in Ocular Oncology Retrospective vision data versus radiotherapy Phase 2 Choroidal Melanoma safety and efficacy data Initiate Pivotal Trial in Choroidal Melanoma IND filing in Choroidal Metastases Public Company Successful IPO 2021

Slide 5

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 Suprachoroidal) Cancers of the Ocular Surface Non-Muscle Invasive Bladder Cancer Other HSPG-Expressing Tumors (e.g., Cutaneous Melanoma, HNSCC) 2022 – Phase 2a safety and efficacy data 2H 2022 – Initiate Phase 2b (pivotal trial) 2H 2022 – IND 2H 2022 – Initiate Phase 1 trial 2023 –Phase 1 data Global Planning for All Product Candidate Indications

Slide 6

Choroidal Metastasis

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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, 138;901–911, February 2016; Kines et al; Molecular Cancer Therapeutics, 17(2) February 2018; Kines et al; Cancer Immunology Research, May 2021 Technology Platform Designed to Target a Broad Range of Solid Tumors Based on  Virus-Like Particles with Multiple Options for Cytotoxic Payloads * HSPGs - Heparan Sulphate Proteoglycans

Slide 8

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 1b/2 Trial in Choroidal Melanoma Kines et al; Cancer Immunology Research, May 2021

Slide 9

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; Kines et al.; International Journal of Cancer, 138;901–911, February 2016; Kines et al.; Molecular Cancer Therapeutics, 17(2) February 2018 Heparan sulfate proteoglycans (HSPGs) are a large family of molecules found in the extracellular matrix (ECM) and on the membranes of cells Tumors specifically modify HSPGs with key sulfation modifications that provide high binding specificity to a number of ligands Tumor modified HSPGs regulate many aspects of tumor progression, including proliferation, invasion, angiogenesis and metastases Our VLPs can selectively bind to tumor modified HSPGs and not to normal cells

Slide 10

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…choroidal metastasis, Progress in retinal and eye research (2019), 2Cohen, Ocular metastasis, Eye (2014), 3Shields et al. Survey of 520 eyes with uveal metastases. Ophthalmology (1997), 4Namad et al. Bilateral choroidal metastasis from non-small lung cancer, Case reports in oncological medicine (2014). Breast 40-53% Lung 20-29% GI 4% Kidney 2% Prostate 2% Skin 2% Common Features of C-Mets3

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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 induced potent cell killing upon light activation with potencies (EC50’s) in the picomolar range

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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 heparin AU-011 demonstrated no cytotoxicity in the absence of light activation

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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 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)

Slide 14

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 using syngeneic mouse models for cancer types known to metastasize to the choroid Significantly inhibits tumor growth and prolongs survival Statistically significant results in multiple tumor models Study results support further evaluation of AU-011 as a potential treatment for choroidal metastasis

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Retrospective Matched Case-Control Study

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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, distance to fovea/ optic disk, visual acuity (all 4 must match) Matching performed by Independent Statistician Patients matched based on tumor size, location, and vision Up to 5:1 AU-011 subjects followed in primary trial and vision results extrapolated Subjects treated with plaque radiotherapy with long term follow up from large center dataset Data from patients treated with AU-011 in the Ph1b/2 study will be compared to patients treated with plaque radiotherapy at 1, 2, 3, 4 and 5 years and at last follow up to support visual acuity benefit AU-011 has the Potential to Have Long Term Visual Acuity Benefit over Plaque Radiotherapy *rmCC – retrospective matched case control

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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 = 0.794** Source Plaque Timepoint Change in logMAR AU-011 Plaque Treatment Difference p-value AU-011 vs. Plaque Year 1 0.199 0.216 -0.017 0.8418 Year 2 0.199 0.443 -0.244 0.0323 Year 3 0.199 0.643 -0.444 0.0006 Year 4 0.199 0.890 -0.691 <.0001 Year 5 0.199 0.992 -0.794 <.0001 Mixed model repeated measures (MMRM) analysis controlling for matching. Comparing last AU-011-101 trial value (average follow up 15.6 months) with plaque timepoints. N=43 AU-011 subjects compared to N=150 matched plaque patients. Multiple imputation to address missing data. Statistically Significant Vision Preservation Starting at 2 Years

Slide 18

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 54.0% <.0001 Year 5 73.3% <.0001 60.1% <.0001 Analysis of the proportion of subjects with a loss of logMAR ≥ 0.3 and ≥ 0.6 via Cochran–Mantel–Haenszel test to control for matching. Multiple imputation to address missing data. Comparing AU-011-101 trial values (average follow up 15.6 months) with Plaque timepoints. Significantly Higher Proportion of Subjects with Loss ≥3 Lines Starting at 2 Years and ≥6 Lines Starting at 3 Years with Plaque Radiotherapy vs. AU-011

Slide 19

AU-011 in Combination with Checkpoint Inhibitors Ruben Huis in t’ Veld

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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)

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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

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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 Cancer cells AU-011 22-jun-22

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AU-011 + light activation can induce cancer cell death 22-jun-22 Viable cell Apoptotic cell Dead cell Control AU-011 + Light activation

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AU-011 treatment can induce cancer cell directed cytotoxicity Cancer cell Dendritic cell Control AU-011 only Light only AU-011 + Light activation

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Damage-associated molecular patterns (DAMPs) Showalter A. et al. Cytokines in immunogenic cell death: Applications for cancer immunotherapy. Cytokine. 2017;97:123-132

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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

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Dendritic cell maturation following AU-011 treatment

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AU-011 + Light activation combined with ICI enhanced treatment response compared to either treatment alone (1 of 2) 22-jun-22

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AU-011 + Light activation combined with ICI enhanced treatment response compared to either treatment alone (2 of 2)

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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

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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

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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

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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 **** **** **** **** **** **** **** **** ****   Survival **** **** **** *** **** **** **** **** **** AU-011 Tumor Volume - ns ns ns ns * ns ns ns   Survival - ns * ns ** *** ** ns *** Significance of the data presented in figure 5, determined by a one-way ANOVA with Tukey correction for multiple comparisons at day 20 post inoculation for tumor volume and a Mantel-Cox test for survival (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001; n ≥ 8). J Clin Oncol 40, 2022 (suppl 16; abstr e14544) 22-jun-22

Slide 35

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 tumors in murine models 22-jun-22

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Acknowledgements Insert > Header & footer Prof. Dr. M. J. Jager & Prof. Dr. F. Ossendorp Aura Biosciences Health Holland Leiden University Medical Center

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Question & Answer

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ISOO 2022 Thank you! Confidential