ANNUAL REPORT 2022
CorporateDirectory Directors Dr Geoffrey Cumming Non-Executive Chairman Mr Robert (Max) Johnston Non-Executive Director Mr Philip Powell Non-Executive Director Prof. Allan Cripps AO Non-Executive Director Chief ExecutiveOfficer Dr Leearne Hinch Chief Financial Officer andCompany Secretary Mr Tony Di Pietro Chief ScientificOfficer Dr Gregory Rice RegisteredOffice and Postal Address 23 Normanby Road Notting Hill Victoria 3168 Telephone: +61 3 9548 7586 Share Registry - Australia Computershare Investor Services Pty Ltd 452 Johnston Street Abbotsford Victoria 3067 Telephone: 1300 850 505 Overseas: +61 3 9145 4000 Auditors - Australia Grant Thornton Audit Pty Ltd 727 Collins Street Melbourne Victoria 3008 Solicitors MinterEllison Level 20, Collins Arch 447 Collins Street Melbourne Victoria 3000 Website www.inoviq.com INOVIQ Limited
INOVIQ Ltd (ASX:IIQ) (INOVIQ®) is developing and commercialising next-generation exosome capture tools and precision diagnostics to improve the diagnosis and treatment of cancer and other diseases. INOVIQ’s vison is to be a leading exosome and precision diagnostics company delivering nextgeneration products to improve patient health outcomes and help save lives. 1 Contents 2 Chairman and CEO Letter 4 2022 Key Highlights 6 Review of Operations 22 Directors’ Report 33 Auditor’s Independence Declaration 34 Consolidated Statement of Comprehensive Income 35 Consolidated Statement of Financial Position 36 Consolidated Statement of Changes in Equity 37 Consolidated Statement of Cash Flows 38 Notes to the Financial Statements 66 Directors’ Declaration 67 Corporate Governance Statement 68 Independent Auditor’s Report 72 Shareholder Information 1 Annual Report 2022 Contents
2 INOVIQ Limited During the period, we advanced our innovative exosome capture tools, precision diagnostic products and pipeline towards a number of key research, development and commercialisation milestones. These achievements were made despite the continuing challenges of the COVID-19 pandemic and volatile financial markets globally, particularly for biotech companies. Evolving the business strategy Through FY22, INOVIQ raised $18.4 million, completed a corporate rebrand and successfully repositioned the business to focus on next-generation exosome capture tools and precision diagnostics. The rebrand fromBARD1 to INOVIQ, which represents ‘intelligent innovation’, better reflects the strategic vision, broader intellectual property assets and expanded product portfolio of the Company. Paving theway for commercialisation One of the key achievements for the year was the launch of our first EXO-NET pan-exosome capture tool for research use. We also successfully completed evaluations of EXO-NET with key research organisations in Australia and overseas, and recently established sales and logistics capabilities for EXO-NET research tools in the US. The appointment of the contract sales team has laid foundations for an accelerated roll-out of EXO-NET products in the US, the largest geographic market segment for the US $661 million global exosome research market. Chairman andCEOLetter R&D activities driving the pipeline Research and development activities during the year focused on progressing the development and transfer of the proof-of-concept SubB2M™ immunoassays to USbased contract research organisation (CRO) ResearchDx. After successfully replicating the assay, ResearchDx are now advancing the SubB2M tests through optimisation and validation, before entering clinical testing for monitoring breast and ovarian cancers. In another important milestone for our SubB2M program, we signed a manufacturing agreement withMP Biomedicals to manufacture our proprietary SubB2M protein under GMP conditions for use in our commercial tests. For EXO-NET we have been focused on expanding the data package for EXO-NET research tools, evaluating new EXO-NET prototypes and progressing The University of Queensland (UQ) collaboration to develop an exosomebased ovarian cancer screening test using EXO-NET. FY22 financial performance INOVIQ reported a net loss from operating activities (after income tax) for the year of $18.2 million. Removing noncash impairment charges, the Group’s operating loss was $5.4 million. Our cash reserves were boosted by $18.4m of new capital that was raised via a private placement and share purchase plan completed in August 2021. We ended the financial year with a strong cash balance of $15.4m that will be used to support our ongoing strategic and operational requirements. Legal proceedings update The Company continues to defend the legal proceeding filed in the Supreme Court of Victoria on 22 February 2021 by TonyWalker and former BARD1 director and Chief Scientific Officer Dr Irmgard Irminger-Finger against the Company. The proceeding has been listed for trial in February 2023. Dear FellowShareholders It is a pleasure to provide INOVIQ’s Annual Report for the period ending 30 June 2022, a period which delivered significant progress for your Company.
3 Annual Report 2022 Bolstering our teamwith key appointments During the year we made several key appointments to the team in order to accelerate our product development and commercialisation strategies. We were extremely fortunate to secure world-leading medical researcher Dr Greg Rice to the position of Chief Scientific Officer and since joining in September 2021, he has been instrumental in driving our R&D programs into the clinical development and commercialisation phase. We also appointed Dr Rocco Iannello to the newly created position of Business Development and Licensing Director, with his expertise already proving invaluable to our IP commercialisation, licensing agreements and EXO-NET roll-out efforts. Looking ahead... While market conditions have been difficult and the journey of a biotech company is never straightforward, we evolved our business and made significant progress this year. With our proprietary technologies and strong development pipeline, current funding, and high-calibre people, INOVIQ is well positioned to advance our multi-product exosome capture tool and precision diagnostics pipeline towards key development and commercialisation milestones in financial year 2023. We expect our SubB2M-based tests for breast and ovarian cancer monitoring to commence clinical studies by December 2022 and be launch-ready as laboratory developed tests in the second half of calendar year 2023. We are also focused on developing new EXO-NET exosome isolation products for research applications and expanding EXO-NET collaborations for development of novel exosome-based diagnostic applications. Additionally, we look forward to progressing the development of the exosome-based ovarian cancer screening test with The University of Queensland. In closing, we would like to thank the INOVIQ team for their unwavering dedication to the Company’s ultimate ambition of improving patient health outcomes in areas of important unmet needs. We also sincerely thank shareholders for your continued support and faith in our company. Dr Geoff Cumming Chairman Dr Leearne Hinch CEO
July 2021 $15 million placement completed to accelerate cancer diagnostic test development August 2021 Proof-of-concept achieved in feasibility studies demonstrating that a SubB2M-based test can detect a biomarker for ovarian cancer in patient samples July 2022 US-based contract sales team engaged to accelerate EXO-NET commercial roll-out September 2021 Dr Greg Rice appointed Chief Scientific Officer (CSO) to accelerate the commercial development of the company’s diagnostic tests November 2021 US patent issued for BARD1 technology, covering autoantibody test for lung cancer December 2021 Company changes its name fromBARD1 to INOVIQ Ltd, representing ‘intelligent innovation’ April 2022 US-based contract diagnostics organisation ResearchDx engaged to further the development and validation of INOVIQ’s SubB2Mbased tests in the USA January 2022 US patent issued for BARD1 technology, covering autoantibody tests for breast and ovarian cancer July 2021 University of Queensland researchers unveil promising results for a exosome-based blood test for ovarian cancer August 2021 Share Purchase Plan successfully completed with oversubscribed applications of $3.4m accepted July 2022 Grant of SubB2MU.S. patent December 2021 Chinese patent issued for BARD1 technology, covering autoantibody test for lung cancer July 2022 Grant of U.S. patent for hTERT April 2022 A Scientific Statement co-authored by INOVIQ’s Chief Scientific Officer, Dr Greg Rice, is published in scientific journal Endocrine Reviews July 2022 Positive SubB2M IHC results for Melanoma achieved May 2022 Australian patent is granted for SubB2M technology April 2022 INOVIQ and The University of Queensland (UQ) expand collaboration to develop a world-first exosome-based ovarian cancer screening test providing INOVIQ with exclusive option to licence intellectual property for commercialisation of diagnostic test 4 INOVIQ Limited 2022 Key Highlights
5 Annual Report 2022
Reviewof Operations BUSINESSOVERVIEW INOVIQ Ltd (ASX:IIQ) (INOVIQ®) is developing and commercialising next-generation exosome capture tools and precision diagnostics to improve the diagnosis and treatment of cancer and other diseases. The Company has commercialised the EXO‐ NET® pan‐ exosome capture tool for research purposes and the hTERT test as an adjunct to urine cytology testing for bladder cancer. INOVIQ’s cancer diagnostic pipeline includes blood tests in development for the earlier detection and monitoring of ovarian, breast and other cancers. HIGHLIGHTS INOVIQ advanced its innovative exosome-based and diagnostic products and pipeline towards key development and commercialisation milestones during the financial year, including: Commercial – Multiple positive evaluations of EXO-NET pan-exosome capture tool were successfully completed by key Australian and US-based research organisations, with data provided to the company for use in its marketing materials – Percorso Life Sciences engaged to provide contract sales and logistics services in the USA. This agreement is a key step toward driving EXO-NET research tool sales in the largest geographic market segment for exosome research products – Plans progressed to transfer, scale-up and manufacture EXO-NET under cGMP conditions at the Company’s Melbourne facility to meet expected demand for EXO-NET research tools and enable future builds of custom-designed products – Master Manufacturing Agreement executed withMP Biomedicals, a global supplier of life science and diagnostic products, for the contract manufacture of INOVIQ’s proprietary SubB2Mprotein to cGMP standard – Multiple patents granted protecting the Company’s NETs, SubB2M, BARD1 and hTERT technologies and products We are pleased to present the Group’s Annual Report for the financial year ended 30 June 2022 and provide an update on further strategic and operational progress since year end. 6 INOVIQ Limited
Research & Development SubB2M – ResearchDx, a US-based specialty contract diagnostics organisation, engaged under a Master Services Agreement to undertake further development and validation of SubB2M-based immunoassay tests for breast and ovarian cancer monitoring – Proof-of-concept achieved for SubB2M-CA125 immunoassay for ovarian cancer at Griffith University. SubB2M technology transferred to ResearchDx and performance of the SubB2M-CA15.3 immunoassay for breast cancer successfully replicated. SubB2M immunoassays progressing to optimisation and validation before advancing to clinical testing for monitoring of breast cancer and ovarian cancer – Positive results from SubB2M immunohistochemistry study demonstrating 91% sensitivity for detection of melanoma and ability to distinguish malignant melanoma from benign lesions. INOVIQ to seek partners to sublicence the further development and commercialisation of SubB2M IHC tissue‐ -based tests – Expanded the feasibility program for INOVIQ’s highly sensitive SubB2M-based SPR test to detect Neu5Gc with a Canadian-based medtech company on its next-generation high-throughput benchtop Surface Plasmon Resonance (SPR) instrument – Paper by researchers at the Institute for Glycomics, Griffith University and University of Adelaide evaluating the use of INOVIQ’s SubB2M technology in breast cancer published in BMCCancer journal EXO-NET – EXO-NET research program focused on development of new exosome research tools to isolate specific exosome subsets for use in targeted disease applications – Promising exosome-based ovarian cancer test data released by collaborator University of Queensland (UQ) showing over 90% accuracy for detection of stage I and II ovarian cancer in a 450-sample retrospective case-control study – Umbrella Research and Option Agreement signed with UQ to develop a world-first exosome-based ovarian cancer screening test using INOVIQ’s EXO-NET capture technology and UQ’s novel exosomal biomarkers – Expanded the EXO-NET data package to support the utility of the EXO-NET Research Use Only (RUO) pan-exosome capture tool to isolate exosomes and its speed, yield and purity advantages over competitor products – Initiated research program to expand EXO-NET research tool portfolio including development of an EXO-NET exosome capture and release tool for research and future therapeutic applications – Scientific Statement, co-authored by INOVIQ’s Chief Scientific Officer, Professor Greg Rice, entitled “Extracellular vesicles and their emerging roles as cellular messengers in endocrinology: An Endocrine Society Scientific Statement” was published in the Endocrine Society’s high impact scientific journal Endocrine Reviews – New data establishing the utility of EXO-NET for On-Bead Analysis of extracellular vesicles, using Fourier Transformed Infrared (FTIR) Spectroscopy was presented at the 2022 International Society for Extracellular Vesicles (ISEV) Annual Meeting held in Lyon, France by INOVIQ and University of Sydney BARD1 – The BARD1 autoantibody research programwas placed under review during the year and no further investment planned until completion of the review Corporate – Capital raising of $18.4m from a Placement and Share Purchase Plan to fund SubB2M and NETs programs – Additional grant funding of $89,331 awarded under MTPConnect’s Biomedical Translation Bridge (BTB) program to support development of INOVIQ’s SubB2M immunoassays for cancer detection. This funding was additional to an earlier $372,654 grant awarded in September 2020 under the BTB program – Professor Greg Rice appointed as CSO and Dr Rocco Iannello appointed Director, Business Development and Licensing to accelerate development and commercialisation of INOVIQ’s research tools and diagnostic tests – Company rebranded INOVIQ to reflect our focus on ‘intelligent innovation’ of next-generation precision diagnostics to enable earlier diagnosis, precise treatment selection and improved patient outcomes – MST Access initiates coverage of INOVIQwith first analyst report, released 25 August 2022, valuing INOVIQ at $2.11 per share (undiluted) Financial – Cash balance of $15.4 million at 30 June 2022 – Audited net loss after tax of $18.2 million for the financial year ended 30 June 2022. Removing non-cash impairment charges, the Group’s operating loss was $5.4 million – Research & Development (R&D) Tax Refund of $1.3m recognised for the 2021 and 2022 financial years 7 Annual Report 2022
STRATEGICOBJECTIVES INOVIQ is driving intelligent innovation in the diagnostic and exosome markets to improve health outcomes for patients with cancer and other diseases. INOVIQ is using its proprietary biomarker isolation and detection technologies, and a multiomics approach to develop next-generation precision diagnostics for the screening, diagnosis, treatment selection and monitoring of cancer and other diseases. The Company has unique technologies, in-market products and a strong development pipeline of exosome capture tools and precision diagnostics intended to improve patient health outcomes in important unmet needs for the earlier detection and monitoring of breast cancer, ovarian cancer and other diseases. INOVIQ remains focused on its vison to be a leading exosome and precision diagnostics company delivering next-generation products to improve patient health outcomes and help save lives. The Group’s key objectives identified in its 3-year strategic plan (set in 2020) are to: Accelerate development of lead SubB2M tests Accelerate development of fast-to-market SubB2M tests for detection and monitoring of breast and ovarian cancers as Laboratory Developed Tests (LDTs) in the USA. Build an exosome liquid biopsy pipeline Build a next-generation exosome diagnostics pipeline using the Group’s EXO-NET technology for early detection of cancer, other serious conditions and companion diagnostic applications. Expand product indications Implement a risk-based, stepped approach to gaining regulatory clearance/approvals for in vitro diagnostic (IVD) products based on obtaining clearance for monitoring uses first, before conducting further clinical studies to expand indications to screening uses in highrisk and then average-risk patient populations. Expand technology applications Expand applications for the Group’s proprietary technologies to areas of significant unmet need in the screening, diagnosis, prognosis and monitoring of various cancers and other diseases to improve patient outcomes and save lives. Commercialise products through partnering Commercialise pipeline products through partnering of LDTs with clinical laboratories and IVDs with specialised distributors to expand international reach and support sales, marketing and distribution of the Group’s diagnostic tests. Generate multiple revenue streams Generate future revenue streams through increased market penetration of the Group’s existing hTERT product, sales of the EXO-NET capture tool for research applications, potential future licensing deals for use of the Group’s IP for diagnostic and therapeutic applications and potential future commercialisation of the Group’s cancer diagnostics pipeline in key markets. These initiatives are aimed at growing long-term shareholder value through accelerating the commercialisation of the Group’s lead diagnostics, building a multi-product pipeline, diversifying risk across multiple applications and creating a sustainable revenue generating business. CANCERDIAGNOSTICSMARKET The global cancer burden is significant with an estimated 50.6 million people living with cancer, 19.3 million new cases and 10.0 million deaths in 2020.1 The incidence of cancer is expected to rise to 28.4 million new cases by 2040 due to population aging and growth. The most common diagnosed cancers worldwide were breast (11.7% of all new cases), lung (11.4%), colorectal (10.0%), prostate (7.3%) and stomach (5.6%) cancers. Cancer is a leading cause of premature death with the highest burdens in China, Europe and North America. The cancer burden can be reduced by improved prevention, early detection, availability of cancer screening programs and effective treatment to improve patient outcomes and reduce mortality. Diagnostics for earlier detection and monitoring could improve treatment options, patient outcomes and survival for this expanding public health crisis. INOVIQ is targeting cancer diagnostic market segments currently valued at over US$15 billion globally for some of the world’s most common and deadliest cancers including breast, ovarian and other cancers. Reviewof Operations 1 Sung H et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence andMortalityWorldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021. https://doi.org/10.3322/caac.21660 8 INOVIQ Limited
UNMETNEEDFOREARLIERCANCER DETECTION Cancer is often detected at late-stage (Stages III and IV) after symptoms have appeared, resulting in a poor prognosis for patients. Earlier detection of cancer increases treatment options, improves patient outcomes and increases 5-year survival rates. Existing diagnostic tests can suffer from high falsepositives and/or insufficient sensitivity for early-stage cancer (stages 1 and II). Additionally, there is often poor screening participation due to existing tests being invasive, inconvenient, inaccessible, or expensive. There is a clear unmet need for non-invasive, accurate and reliable tests for earlier detection of cancer. 5-year survival rates by stage at diagnosis The Group is well positioned to develop and commercialise cancer diagnostic products for the screening, diagnosis, prognosis and monitoring of multiple cancers based on our proprietary technologies. EXOSOMESHAVEHUGEPOTENTIAL AS NOVEL BIOMARKERS FORMULTIPLE DISEASESANDAPPLICATIONS Exosomes are small extracellular vesicles (EVs) released by all cells. They are nanometre-sized lipid membrane packages that encapsulate (and protect from degradation) DNA, RNAs and proteins. EVs and the messages they carry form part of the cell-to-cell communicatione system and play an important role in health and disease. Intercepting and reading EVmessages has important applications in the research, diagnosis and treatment of many diseases, including: cancer, cardiometabolic, inflammatory, neurodegenerative and other diseases. Clinical interest in exosomes has grown exponentially due to their commercial potential in drug delivery, disease diagnosis and treatment of cancer. Advancements in exosome research have been limited by slow, impure and inefficient traditional methods to isolate exosomes. There is an unmet need for fast, precise and scalable isolation of exosomes for research and commercial applications. INOVIQ has developed a rapid and efficient way (EXO-NET) to isolate EVs from biofluids to intercept and decode the messages that they contain. This information can be used for assessing patient well-being or disease risk, diagnosis of disease, selecting the best treatment option, or monitoring a patient’s response to treatment. 6% 28% 6% 30% 3% 30% 77% 90% 21% 49% 10% 98% 96% 99% 59% 93% 39% 100% 0% 20% 40% 60% 80% 100% 120% Bladder Breast Lung Ovarian Pancreatic Prostate Late Average Early 9 Annual Report 2022
Reviewof Operations 2 2022. Exosome ResearchMarket - Global Forecast to 2026. Markets&Markets. 3 2022. Exosomes Market Size, Share, Analysis Report byWorkflow, Biomolecule Type, Application and Region, Forecast 2022 - 2030. Acumen Research and Consulting. 4 Food and Drug Administration (FDA) 5 PreMarket Notification (510k) 6 PreMarket Approval (PMA) The global exosome research market was valued at US$144 million in 2021 and is expected to reach US$661 million by 2026, growing at a CAGR of 35.6%.2 North America is the largest geographic segment representing 41.5% of the market followed by Europe at 20%. The Kits and Reagents product segment in which INOVIQ’s EXO-NET research tools fit, was valued at US$71 million in 2021 and is forecast to reach US$311 million by 2026. The global exosomes market for diagnostics and therapeutics was valued at US$168 million in 2021 and is expected to reach US$2.3 billion by 2030, growing at a CAGR of 34% per annum.3 North America is the largest geographic segment. Market growth is driven by increased investment in exosome-based therapeutic R&D, rising incidence of cancer and higher prevalence of chronic inflammatory diseases. PRODUCT PORTFOLIO INOVIQ’s product portfolio includes a research tool for exosome capture, an adjunctive diagnostic test for use in bladder cancer detection, and a broad pipeline of diagnostic tests in development for detection and monitoring of breast, ovarian and other cancers based on our proprietary technologies. Our diagnostics pipeline includes SubB2M tests in development for monitoring breast and ovarian cancers and an exosome-based ovarian cancer screening test. The commercialisation strategy for INOVIQ’s diagnostic pipeline is to first launch its tests as laboratory developed tests (LDTs), followed by an FDA4 In Vitro Diagnostic (IVD) submission and clinical studies to support 510k clearance5 or PMA6 depending on the indication for use. Discussions with clinical and regulatory experts are ongoing as the Company advances its diagnostic development programs towards clinical development and commercialisation. PRODUCT INDICATION PLATFORM USE RESEARCH ASSAY DEVELOPMENT CLINICAL DEVELOPMENT REGISTRATION hTERT Bladder Cancer ICC Adjunct to cytology In-market EXO-NET-RUO Exosome Capture Device Research tool In-market Exosome-OC (UC) Ovarian Cancer Multiomic Screening (TBA) SubB2M-BCM Breast Cancer Immunoassay Monitoring 2023 SubB2M-OCM Ovarian Cancer Immunoassay Monitoring 2023 SubB2M-PCS Prostate Cancer Immunoassay Detection SubB2M-PaC Pancreatic Cancer Immunoassay Detection BARD1-Ovarian1 Ovarian Cancer Immunoassay Detection BARD1-Breast1 Breast Cancer Immunoassay Detection BARD1-Lung1 Lung Cancer Immunoassay Detection Products and pipeline *RUO = Research Use Only; ICC = Immunocytochemistry; 1. Adjunct to urine cytology to assist the detection of bladder cancer; 2 Umbrella Research & Option Agreement with UQ, 3. Progression subject to completion of review (ASX: 28/3/22) 17 | 9 AUGUST 2022 COMMERCIAL PROGRESS Commercial activities during the year focused on completing evaluations of the EXO-NET pan-exosome capture tool, establishing sales and logistics capability for US market launch of EXO-NET, and supporting our hTERT distributors. EXO-NET® exosome capture tools EXO-NET pan-exosome capture is a research use only product for the isolation of exosomes from blood and other body fluids with speed, purity and yield advantages over traditional exosome isolation methods. EXO-NET meets an unmet need for fast, precise and scalable isolation of exosomes for research and commercial applications. EXO-NET pan-exosome capture is a research tool in-market for the isolation of exosomes from body fluids including plasma, urine, and saliva. The product is offered for research use only (RUO) and is not registered for use in clinical diagnosis. EXONET RUO is supplied in 1mL vials containing EXO-NET coated magnetic beads for processing up to 50 samples. 1 BARD1 Autoantibody program currently on-hold pending review 10 INOVIQ Limited
EXO-NET is initially being commercialised as an exosome isolation tool for use in the rapidly growing exosome research market with the goal of embedding the technology into research applications that may underpin future licensing of EXO-NET for use in the development and commercialisation of exosome-based diagnostic and therapeutic applications. EXO-NET pan-exosome capture tool was initially test marketed to exosome researchers inMay 2021. During FY22, INOVIQ completed multiple positive evaluations of its EXO-NET product with leading Australian and international research groups with the goal of gaining product endorsement, generating future sales or securing future collaborations for development of exosome-based diagnostics for cancer, neurodegenerative disease and other indications. Researchers compared EXO-NET to existing exosome isolation technologies with positive results for their biomarkers of interest. On 10 November 2021, INOVIQ sponsored and attended the virtual Australia & New Zealand Society of Extracellular Vesicles (ANZSEV) Symposium to promote and educate researchers about the benefits of EXO-NET. A copy of the conference presentation is available via INOVIQ’s investor centre at www.inoviq.com/site/investors/presentations. On 1 April 2022, INOVIQ announced its first EXO-NET collaboration with the University of Queensland (UQ) to develop a world-first exosome-based ovarian cancer screening test using INOVIQ’s EXO-NET technology and UQ’s biomarkers. This blood test could fill an important unmet need for an accurate and reliable screening test for ovarian cancer to improve women’s health outcomes and save lives. On 26 April 2022, a Scientific Statement, co-authored by INOVIQ’s Chief Scientific Officer Professor Greg Rice, entitled “Extracellular vesicles and their emerging roles as cellular messengers in endocrinology: An Endocrine Society Scientific Statement” was published in the Endocrine Society’s high impact scientific journal Endocrine Reviews. The paper is available at https://doi. org/10.1210/endrev/bnac009. EXO-NET® pan-exosome capture 11 Annual Report 2022
Reviewof Operations 7 Stewart,T et al. Differential detection of cancer-derived extracellular vesicles using combined antibody functionalized magnetic beads and infrared spectroscopy. ISEV 2022. 8 Allison et al. Evaluation of Sienna Cancer Diagnostics hTERT Antibody on 500 Consecutive Urinary Tract Specimens. Acta Cytologica 2018. DOI: 10.1159/000489181 On 27 May 2022, Professor Rice presented a poster titled ‘Differential detection of cancer-derived extracellular vesicles using combined antibody functionalized magnetic beads and infrared spectroscopy’, at the 11th International Society of Extracellular Vesicles (ISEV) Annual Meeting in Lyon, France on behalf of INOVIQ and University of Sydney.7 This data showed that direct Fourier Transformed Infrared (FTIR) analysis of EVs captured by EXO-NET was able to classify different cancer cell types. Clinical applications for this method may include accurate disease classification and triage-to-treatment. The poster is available at https:// www.inoviq.com/site/technology/publications. The ISEV conference provided a valuable opportunity to showcase the EXO-NET exosome capture technology and data to potential research collaborators, commercial partners and customers. Post year-end, on 21 July 2022, INOVIQ engaged USbased Percorso Life Sciences to provide sales and logistics services to accelerate the commercial roll-out of EXO-NET research products in the USA. This agreement is a key step toward driving EXO-NET research tool sales in what is the largest geographic market segment for exosome research products globally. The sales force will cover the key east-coast, west-coast and mid-west US regions, and target academia and biopharma customers in its sales and marketing of EXO-NET research tools. Percorso will also provide inventory, logistics and warehousing services. EXO-NET can be ordered from its sales team in the USA or online at www.exo-net.com in the rest of world. The Company continues to engage with other potential commercial partners to distribute EXO-NET RUO in other regions to expand its international reach and support sales, marketing, and distribution of the product for research applications. hTERT ICC test The hTERT test is an immunocytochemistry (ICC) assay registered for the detection of human telomerase reverse transcriptase (hTERT) in cytopathology samples. It is used as an adjunct to urine cytology to help resolve indeterminate cytology results and identify patients with increased risk of bladder cancer. Telomerase is an enzyme used by 85% of epithelial cancers to enable immortal cell replication. This occurs through the role that telomerase plays in the repair of chromosome ends called telomeres. Telomeres normally shorten with each successive cell division until the cell dies in a process called senescence. Telomerase counteracts this telomere shortening process by adding new telomeric repeat sequences, effectively repairing the telomere ends. hTERT is a component of telomerase that is present in 90% of urothelial carcinomas. The hTERT test is registered as an IVDmedical device in the United States (Class I IVD), Europe (CE-IVDmarking), Australia (Class I IVD) and South Korea (Class II IVD) for use as a clinical diagnostic by pathology laboratories for the detection of hTERT in cytopathology samples. It is used by pathologists as an adjunct to urine cytology to help resolve indeterminate cytology results and identify patients with increased risk of bladder cancer.8 The hTERT test is currently earning revenues from the US and is in the early commercialisation phase in other markets. Distributors have been appointed in China, Greece, Israel, Sweden, and South Korea. Revenues from hTERT sales remained lower than preCOVID-19 pandemic levels during FY22, with the Group’s hTERT test achieving revenues of $276,745 (2021: $468,096). While hTERT sales are not expected to substantially increase over the next 12 months, INOVIQ continues to work with its distributors to improve sales and progress hTERT validations by new laboratories. Registration of the hTERT test by the Chinese distributor was delayed at the National Medical Products Administration (NMPA) due to COVID-19 restrictions. HTERT ICC test 12 INOVIQ Limited
RESEARCH&DEVELOPMENT PROGRESS Our technologies have the potential to deliver significant commercial and clinical benefits to patients, the healthcare system and our shareholders. R&D activities during FY22 focused on progressing and transferring the SubB2M immunoassays to a contract diagnostics organisation for optimisation and validation, securing GMPmanufacture of SubB2M, expanding the EXO-NET data package, evaluating new EXO-NET prototypes and progressing the UQ collaboration for development of an exosome-based ovarian cancer test. SubB2M program SubB2M is an engineered protein that specifically binds the pan-cancer biomarker Neu5Gc that is found at elevated levels in multiple human cancers. INOVIQ is developing SubB2M-based tests for multiple uses including monitoring of breast and ovarian cancers, and for a general health panel. INOVIQ’s SubB2M/CA15.3 and SubB2M/CA125 immunoassays are being developed to improve the sensitivity and specificity of existing standard of care cancer biomarker tests for monitoring of breast and ovarian cancer, respectively. During the year, the SubB2Mprogram focused on completing feasibility studies to design, build and test prototype SubB2M immunoassays for breast and ovarian cancer at Griffith University, followed by technology transfer to a US-based contract diagnostics organisation for further optimisation and validation. Contract manufacture of the SubB2Mprotein under GMP conditions was also established for use in the commercial SuB2M tests. On 17 August 2021, INOVIQ announced that proof-ofconcept (POC) had been achieved for its SubB2M/CA125 immunoassay for ovarian cancer. INOVIQ’s collaborator, the Institute for Glycomics at Griffith University (Griffith), demonstrated that an initial SubB2M/CA125 assay could detect CA125-Neu5Gc in serum from stages I-IV ovarian cancer (OC) patients compared to healthy controls at biologically relevant levels. On 6 April 2022, INOVIQ announced that a paper, entitled, “N glycolylneuraminic acid serum biomarker levels are elevated in breast cancer patients at all stages of disease”, was published in the international peer reviewed journal, BMCCancer, by researchers fromGriffith University’s Institute for Glycomics and the University of Adelaide. The paper discussed the full data, methods and results underlying the previously announced (15 February 2021) poster presentation showing that a SubB2M-SPR test can be used to distinguish all stages of breast cancer (n=96) from cancer-free control (n=22) blood samples with over 95% sensitivity and 100% specificity, in the samples tested. 13 Annual Report 2022
Reviewof Operations Researchers concluded that “Neu5Gc serum biomarkers are a promising new tool for disease monitoring for breast cancer that may complement current imaging and biopsybased approaches.” The paper is available at https://www. inoviq.com/site/technology/publications. On 5 April 2022, INOVIQ announced it had partnered with US-based specialty contract diagnostics organisation, ResearchDx, under a Master Services Agreement to further the development and validation of its SubB2M immunoassay tests. ResearchDx offers a ‘start-tofinish’ partnership for the development of LDTs, in vitro diagnostics (IVDs) and companion diagnostics (CDx) including the design, development, validation and registration of diagnostics. Additionally, ResearchDx operates a high-complexity CAP9/CLIA10 certified laboratory, PacificDx. This makes ResearchDx is an ideal partner for INOVIQ’s SubB2M-based LDTs in the USA where the tests can be developed and validated for their intended use in the PacificDx clinical laboratory and offered to hospitals, clinicians and doctors’ offices to aid in the detection and monitoring of cancer. On 2 May 2022, INOVIQ announced it had partnered withMP Biomedicals Asia Pacific Pte Ltd under a Master Manufacturing Agreement for contract manufacture of the SubB2Mprotein to cGMP standard at its ISO 13485 certified Singapore facility. The agreement withMP Biomedicals enables a streamlined, scalable and costeffective production process for continuity of supply of the SubB2Mprotein for our commercial SubB2M tests. Post year-end, on 1 July 2022, INOVIQwas pleased to report that the performance of the SubB2M-CA15.3 assay for detection of breast cancer, initially developed by Griffith University, had been successfully replicated by ResearchDx. INOVIQ is now working with ResearchDx to advance the optimisation and validation of the SubB2M-CA15.3 assay, before advancing to clinical testing for breast cancer monitoring. The SubB2M-CA125 assay for ovarian cancer is also planned to undergo further development, optimisation and clinical testing for ovarian cancer monitoring. SubB2M immunohistochemistry (IHC) studies were also conducted to assess the utility of the cancer-associated biomarker Neu5Gc (using INOVIQ’s SubB2M cancer probe) to discriminate between benign skin lesions, malignant and metastatic melanoma. Post year-end on 26 July 2022, INOVIQ reported results from the melanoma 9 College of American Pathologists (CAP) accredited. CAP accreditation ensures laboratories meet industry standards fromCLIA, FDA and OSHA for test accuracy and patient diagnosis 10 Clinical Laboratory Improvement Amendments (CLIA) certified. CLIA regulates laboratory testing and requires clinical laboratories to be certified by the Center for Medicare andMedicaid Services (CMS) before they can accept human samples for diagnostic testing. 14 INOVIQ Limited
IHC study of 144 tissue samples that demonstrated SubB2M staining score was significantly greater in malignant and metastatic samples when compared to benign (p < 0.003 and p < 0.03, respectively). Cells staining positive for SubB2M approached 100% in malignant and metastatic tissues. The ability of SubB2M IHC to correctly classify melanoma tissue samples was further assessed by Receiver Operating Characteristic Curve (ROC) analysis using a logistic regression model with 10-fold cross validation. The area under the ROC was 0.79, with the SubB2M IHC test correctly classifying 91% of malignant and metastatic melanoma tissue samples. Previous proof-of-concept studies by Griffith University showed compelling preliminary results for detection of breast and ovarian cancers with over 95% sensitivity and 100% specificity across all stages on a surface plasmon resonance (SPR) platform. Post year-end, on 29 July 2022, INOVIQ advised it had expanded its feasibility program for a highly sensitive SubB2M-based SPR11 test with a Canadianbased medtech company. The new SPR instrument allows for high throughput sample processing that could be performed in a central laboratory to detect Neu5Gc concentrations in a general health panel. Increased Neu5Gc concentrations in the blood may provide an early warning that an individual requires follow-up investigation for the presence of certain types of cancer such as breast, ovarian, prostate, pancreatic, kidney and melanoma.12 EXO-NET program EXO-NET is an immunoaffinity magnetic-bead capture technology that uses a proprietary multiantibody matrix coated on nanobeads to isolate exosomes based on their surface markers. The DNA, RNA, protein and lipid biomolecules found in exosomes have important applications in the research, diagnosis and treatment of cancer, inflammatory, metabolic, and neurodegenerative diseases. EXONET can be customized to capture specific types of EVs and can be fully-automated for high-throughput sample analysis for large scale clinical trials or routine pathology or CLIA laboratory applications. INOVIQ’s goal is to develop a portfolio of EXO-NET capture tools and EXO-NET powered exosome-based diagnostics for detection of cancer and other diseases. INOVIQ is engaging with key opinion leaders focused on exosome research to establish research collaborations for the development of more accurate and reliable exosome-based diagnostics. The Company expects to advance new EXONET collaborations with key opinion leaders for exosomebased capture tools and diagnostics for other cancers and diseases over the next 12-months. During the year, INOVIQ completed extensive in-house studies to develop a robust data package evidencing the utility of its EXO-NET Research Use Only (RUO) panexosome capture tool and its advantages over competitor products. Amanuscript is being prepared for publication 11 SPR = Surface Plasmon Resonance 12 Internal Griffith University SPR and INOVIQ IHC data 15 Annual Report 2022
Reviewof Operations based on these in-house data comparing the performance of EXO-NET RUO to competitor exosome capture tools. Publication of these data is expected to generate additional research interest in EXO-NET and lead to further research collaborations, potential partnering opportunities and sales of EXO-NET. Multiple independent evaluations of EXO-NET were successfully completed by Australian and US research organisations that reported strong positive feedback. The data generated by these groups will be included in technical and marketing documentation to support future sales of the product. On 28 July 2021, INOVIQ announced that its collaborator, University of Queensland (UQ) had released promising data for its potential exosome-based ovarian cancer test. INOVIQ’s EXO-NET RUO product was used by the UQ researchers to isolate exosomes from the blood of ovarian cancer patients within 15 minutes, with high purity and yield. On 1 April 2022, INOVIQ announced it had expanded its collaboration with The University of Queensland (UQ) to develop a world-first exosome-based ovarian cancer screening test. The objective of these studies is to validate a multivariate index assay for the earlier detection of ovarian cancer. EXO-NET represents a scalable method for translating exosome-based assays into routine pathology and CLIA laboratory workflows. The studies will use EXO-NET to confirm the performance of the 7 exosomeassociated biomarkers currently used in the algorithmbased assay and aims to identify other informative exosome-associated miRNA and protein biomarkers that may improve the performance of the current algorithm. UQ will then use EXO-NET in the further development of the exosome-based ovarian cancer test, under a $2.7 million grant from the Australian governments Medical Research Future Fund (MRFF), that includes the clinical validation of the multiomic algorithm in a large independent cohort of samples. INOVIQ has an exclusive worldwide option to license UQ’s intellectual property for the development and commercialisation of the exosome-based ovarian cancer screening test. On 29 April 2022, INOVIQ advised that it is progressing plans to scale-up EXO-NET manufacture to meet expected demand for both its EXO-NET pan-exosome product and for custom-designed products to capture specific exosome subsets. INOVIQ is investing in manufacturing infrastructure to provide a 10-fold increase in production capacity to allow it to service both the research market and strategic diagnostic and therapeutic collaborations/ partnerships. INOVIQ is currently in the process of transferring the production of EXO-NET from its US research laboratory to its Australian facility for commercial manufacture under GoodManufacturing Process (GMP) conditions. GMP production of EXO-NET will provide strict quality control, agility to build customer-specific exosome isolation tools and provide entree into therapeutic markets. The EXO-NET research program is also focused on designing, building and testing new EXO-NET prototypes for capture and/or release of specific exosome subsets that may be relevant in targeted disease applications. On 27 July 2022, INOVIQ advised that it had progressed development of an EXO-NET exosome capture and release tool and provided it to a biotechnology company for evaluation. Initial evaluation of the product has provided positive data. This CR-NET prototype provides the basis for the development of high-capacity systems for the isolation of exosomes for therapeutic applications and, when optimized, will be produced at the newGMP facility in Melbourne. Research is ongoing with several collaborations being progressed with academic and industry groups with the aim of supplying pan or customised EXO-NET’s to partners for use in research and development of exosomebased diagnostics and therapeutics. BARD1 program The BARD1 technology is a biomarker platform that includes BARD1 DNA, RNA, protein, and autoantibodies that have potential application for earlier detection of breast, ovarian and lung cancers. Splice variants of BARD1 have been associated with cancer formation, progression, and poor prognosis. Splice variants of the BARD1 protein play a potential role in cancer formation, progression and prognosis. Previously, autoantibodies (AAbs) to these BARD1 splice variants have been identified across all stages of some cancers, including the early-stage diseases (Stages I and II) before symptoms are present. BARD1 AAbs potentially reflect the early immune response to tumour formation, which may enable BARD1 AAb tests to detect cancer earlier, before symptoms appear. Previously, the Company and its collaborator University of Geneva (UNIGE) performed exploratory, case-control studies showing initial high accuracy of BARD1 AAb tests for the detection of ovarian, breast and lung cancers compared to healthy controls on the Meso Scale Diagnostic platform. These research-stage BARD1 AAb tests were designed to measure autoantibodies to BARD1 variant proteins and their ability to determine the presence or absence of cancer using an algorithm. Subsequently, the Company contracted the development of a prototype RUO 20-plex BARD1 AAb kit on the Luminex platform that was evaluated by both UNIGE and Griffith University. The results showed that using two BARD1 peptides in combination with CA125 levels less than 70 16 INOVIQ Limited
Units/ml provided a sensitivity of 91% and specificity of 50% for detection of ovarian cancer, compared to 27% sensitivity using CA125 alone in this sample group. The high sensitivity obtained by combining the BARD1 peptides with CA125 is encouraging for the potential use of the BARD1 AAb assay for detection of ovarian cancer in high-risk women with Hereditary Breast and Ovarian Cancer syndrome (HBOC), where high sensitivity is important. During FY22, INOVIQ initiated a comprehensive review of the BARD1 autoantibody program and data generated at both UNIGE and Griffith University to inform further research direction, assay design and future studies. Whilst the BARD1 autoantibody assay for detection of ovarian cancer (and other cancers) has shown promising data in several case-control studies, the Company is undertaking further assessment to determine the future development path and commercial potential of this test as it believes the assay still requires considerable further optimisation and analytical validation before advancement towards clinical development of a potential commercial test. Additionally, the Company evaluated BARD1 isoformmRNA approaches in combination with its NETs technology as an alternative to BARD1 autoantibodies for early cancer detection. On 29 November 2021, INOVIQ announced a new exosome liquid biopsy project to evaluate exosome-based BARD1 RNA tests for the earlier detection of breast and ovarian cancers. The Company signed a Research Agreement with the Mucosal Immunology Research Group (MIRG) at Griffith University. These proof-of-concept studies aimed to compare NanoString Technologies and RT-qPCR analyses of exosomal BARD1 RNA biomarkers. This work program is yet to be completed. On 28March 2022, INOVIQ advised that it is continuing its review of the BARD1 autoantibody program, and while that review is being undertaken no further investment in the technology is planned. A decision will be made about further investment at the completion of the review process. The review of the BARD1 autoantibody program remains ongoing as at the date of this Annual Report. Other research projects In April 2022, INOVIQ advised that it had provided notice to end its collaboration with the University of Liverpool to evaluate protein biomarkers for Type 3c diabetes mellitus. The research programwas not progressed in a timely manner due to COVID-19 related delays and INOVIQmade the decision to focus its investment on its core SubB2M and EXO-NET programs for cancer and other diseases. 17 Annual Report 2022
Reviewof Operations INTELLECTUAL PROPERTYPORTFOLIO The Group owns or exclusively licenses a broad intellectual property (IP) portfolio of granted patents, patent applications, trade secrets and trademarks protecting its core technologies, products, processes and brands. The Group had 42 granted patents, 14 patents pending and 2 international (PCT) applications as at 22 July 2022, covering its SubB2M, Molecular NET, BARD1, and hTERT technologies and products across key jurisdictions including the United States, Europe, Asia, and Australia. The Group also owns registered trademarks for INOVIQ®, EXO-NET® and Acuris®. During FY22, the following patents were issued: – On 12 November 2021, INOVIQ announced that US Patent No 11137402 titled ‘Lung Cancer Diagnosis’ was issued by the United States Patent and Trademark Office. – On 24 December 2021, INOVIQ announced that Chinese Patent ZL 201480071075.7 titled ‘Lung Cancer Diagnosis’ was issued by the Chinese Patent Office. – On 17 January 2021, INOVIQ announced that US Patent 11,193,944 titled ‘Kits for detecting breast or ovarian cancer in a body fluid sample and use thereof’ was issued by the United States Patent and Trademark Office. – On 23 February 2022, INOVIQ announced that Brazilian Patent 112013003506 titled ‘BARD1 isoforms in lung and colorectal cancer and use thereof’ was issued by the National Institute of Industrial Property (INPI). – On 3 May 2022, INOVIQ announced that Australian Patent No 2017358401 titled ‘Subtilase cytotoxin B subunit mutant’ was issued by IP Australia to Griffith University and the University of Adelaide. INOVIQ Ltd holds the exclusive worldwide rights to the SubB2M intellectual property for diagnostic applications. – Post year-end, on 1 July 2022, INOVIQ announced that US Patent No 11,371,033 titled ‘Subtilase cytotoxin B subunit mutant’ was issued by the United States Patent and Trademark Office. – On 22 July 2022, INOVIQ announced that US Patent No 11,391,738 titled ‘Method of detecting cancer’ was issued by the United States Patent and Trademark Office to Sienna Cancer Diagnostic Ltd, a subsidiary of INOVIQ. INOVIQ Patent Status Summary Strong patent portfolio • Broad patent portfolio protecting IIQ’s core biomarker isolationand detection technologies and products • IP owned or exclusively licensed • 42 granted patents, 14 pending and 2 international (PCT) applications (at 22/7/22) • Protection across key jurisdictions (including US, Europe, Asia & Australia) • Registered trademarks for INOVIQ® and EXONET® Patent Family Title Granted Pending Expiry SubB2M PCT/AU2017/051230 (WO 2018/085888) Subtilase cytotoxin B subunit mutant AU, US BR, CA, CN, EP, IN, JP, KR, US (cont) 2037 PCT/AU2022/050470 Methods of analysing a sample 2042 BARD1 PCT/FR01/02731 (WO/2002/018536) Truncated BARD1 protein, and its diagnostic and therapeutic uses US 2024 PCT/IB2011/053635 (WO/2012/023112) BARD1 isoforms in lung and colorectal cancer and use thereof AU, BR, CA, CN, CN(div) EP, HK, IL, JP, JP(div), SG, US, US (cont) 2031 PCT/IB2011/054194 (WO/2012/038932) Kits for detecting breast or ovarian cancer in a body fluid sample and use thereof EP, US, US (cont) 2031 PCT/EP2014/073834 (WO/2015/067666) Lung Cancer Diagnosis AU, CN, IL, JP, SG, KR, US CA, EP, HK 2034 EP14002398.7 Non-coding RNA as diagnostic marker and treatment target US 2035 hTERT PCT/AU2015/050060 (WO2015/120523) Method of resolving inconclusive cytology to detect cancer AU, CN, EP, IL, JP, US, US(cont) 2035 PCT/AU2016/050764 (WO2017/027928) Method of detecting cancer in morphologically normal cells JP US 2036 Molecular NETs PCT/US2010/058086 (WO2011/066449) Devices for detection of analytes CN, US(cont1), US(cont2), US(cont3) US(cont5) 2030 PCT/US2013/049779 (WO2014/011673) Molecular Nets EP 2033 PCT/US2014/029823 (WO2014/153262) Molecular nets on solid phases AU, CN CA 2034 PCT/AU2022/050428 Methods relating to tumour-derived extracellular vesicles 2042 cont = continuation; div = divisional 25 | 9 AUGUST 2022 18 INOVIQ Limited
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