Centre For Genomic Regulation

Initial $7.5 Million Strategic Investment Strategic Partnership Opens Pathway to Access Greater China Market Strengthened Balance Sheet and Three-Year Extension of Existing Debt Terms REDWOOD CITY, CA / ACCESSWIRE / March 6, 2024 / Avinger, Inc. (Nasdaq:AVGR), a commercial-stage medical device company developing and marketing the first and only intravascular image-guided, catheter-based systems for diagnosis and treatment of vascular disease, today announced a new strategic partnership with Zylox-Tonbridge Medical Technology Co., Ltd. (2190.HK, "Zylox-Tonbridge"), a leading medical device company in the neuro- and peripheral-vascular interventional market in China. Based in Hangzhou, China and listed on the Hong Kong Stock Exchange, Zylox-Tonbridge has developed and launched 36 products into the Greater China interventional markets since its founding in 2012. With a sales and marketing organization of more than 130 people and a vast distribution network, Zylox-Tonbridge achieved the equivalent of approximately $58 million in sales in the most recently reported 12-month period (ended June 30, 2023), representing a growth rate of greater than 50% compared to the prior year period. The strategic partnership provides up to $15 million of equity funding from Zylox-Tonbridge in two tranches, a licensing agreement providing access for Avinger's products in the Greater China region, and a technology transfer agreement to build cost-efficient manufacturing capacity to support global sales. In addition, the parties have signed a strategic collaboration agreement which provides the opportunity for Avinger to access certain Zylox-Tonbridge peripheral vascular products for distribution in the U.S. and Germany. Key Terms of Financing Agreement Under the terms of the financing agreement, Zylox-Tonbridge will invest up to $15 million into Avinger through the purchase of preferred and common stock in two tranches. The initial $7.5 million investment was priced at-the-market under Nasdaq rules at a purchase price of $3.66 per share on an as converted to common stock basis. A second tranche of $7.5 million will be funded upon achieving key milestones, including successfully registering Zylox-Tonbridge as a manufacturer of Avinger's products with the U.S. Food & Drug Administration ("FDA") and Avinger achieving $10 million in aggregate revenue over four consecutive quarters. Avinger's obligation to accept conversion of the initial shares of preferred stock and issue and sell shares of preferred stock upon completion of the milestones are each subject to receipt of the approval of Avinger's stockholders. Concurrent with the Zylox-Tonbridge first tranche investment, CRG Partners, the primary holder of Avinger debt and preferred equity exchanged its Series A preferred stock with an aggregate liquidation preference of approximately $60 million for new Series A-1 preferred stock with a value of $10 million. The new Series A-1 preferred stock is convertible at the same price as the Zylox-Tonbridge transaction and carries no liquidation preference or dividends. Additionally, CRG extended principal payments on Avinger's debt from the first quarter of 2024 to the first quarter of 2027, with interest payments accruing during this time. Key Terms of License, Technology Transfer and Strategic Collaboration Agreement Under the terms of the license and technology transfer agreement, Zylox-Tonbridge has exclusive rights to distribute and manufacture Avinger's proprietary image-guided devices in the Greater China region, including mainland China, Hong Kong, Macao, and Taiwan (the "Territory"). Zylox-Tonbridge will lead all regulatory activities for the registration of the Avinger products in the Territory. Avinger will supply product to Zylox-Tonbridge until such time Zylox-Tonbridge's manufacturing capability has been established. All sales of Avinger products in the Territory will be royalty bearing to Avinger. In addition, the parties have signed a strategic cooperation framework agreement, which provides the opportunity for Avinger to access certain Zylox-Tonbridge peripheral vascular products for distribution in the U.S. and Germany. The agreement also provides the option for Avinger to source finished goods from Zylox-Tonbridge following registration of their manufacturing facility with the FDA. "We are excited to announce this strategic transaction with Zylox-Tonbridge, a dynamic leader in the peripheral interventional market in China," said Jeff Soinski, Avinger's President and CEO. "Our broad-reaching partnership creates an exciting new pathway for Avinger products to enter the large and growing Greater China market through an established commercial channel. It also provides the opportunity for a more cost-efficient manufacturing structure to support the growth of global sales, as well as the potential for Avinger to access Zylox-Tonbridge's high-quality peripheral products for distribution in the U.S. and Germany." Dr. Jonathon Zhao, Chairman and CEO of Zylox-Tonbridge, said, "We are pleased to partner with Avinger to provide Chinese healthcare professionals and patients with cutting-edge medical technologies and disruptive innovative products. We believe this collaboration will expand the company's Peripheral Vascular Intervention product portfolio, reinforce our market leadership, and accelerate the growth of the vessel preparation business in China's peripheral vascular intervention market. By leveraging our leading manufacturing capabilities and working with Avinger, we are confident in bringing patients more cost-efficient and high-quality products. We are looking forward to cooperating with global partners to share growing market opportunities by offering high-quality and affordable innovative medical products and services." Mr. Soinski continued, "Concurrent with this transaction, we have significantly improved our balance sheet with a cash infusion, the exchange of our Series A preferred stock for new Series A-1 preferred stock, and the deferral of principal payments on our existing debt for three years. Combined, these transactions represent a strong show of confidence in our product portfolio. "With this transaction, we have positioned Avinger to access exciting new growth opportunities in China and improve its operating cost structure as global manufacturing comes online. We have also provided the opportunity for new revenue growth and increased sales productivity in our current markets through the potential distribution of Zylox-Tonbridge products in the U.S. and Germany. We are excited to move forward in 2024 as we continue to drive sales of our best-in-class commercial peripheral products and ready our groundbreaking image-guided coronary CTO-crossing device for IDE submission later this year." Detailed terms of the Zylox-Tonbridge transaction will be filed on Form 8-K with the United Stated Securities and Exchange Commission. About Avinger, Inc. Avinger is a commercial-stage medical device company that designs and develops the first image-guided, catheter-based system for the diagnosis and treatment of patients with vascular disease in the peripheral and coronary arteries. Avinger is dedicated to radically changing the way vascular disease is treated through its Lumivascular platform, which currently consists of the Lightbox series of imaging consoles, the Ocelot and Tigereye® family of chronic total occlusion (CTO) catheters, and the Pantheris® family of atherectomy devices for the treatment of peripheral artery disease (PAD), estimated to affect more than 200 million people worldwide. Avinger is developing its first product application for the treatment of coronary artery disease (CAD), an image-guided system for CTO-crossing in the coronary arteries, which provides the opportunity to redefine a large and underserved market. Avinger is based in Redwood City, California. For more information, please visit . Follow Avinger on Twitter and Facebook. About Zylox-Tonbridge Zylox-Tonbridge is one of the leading players in the neuro- and peripheral-vascular interventional medical device market in China. The Company was founded in 2012 and is headquartered in Hangzhou, China. As an integrated medical device company supported by in-house R&D and manufacturing capabilities, proprietary technological platforms, and commercialization capabilities, Zylox-Tonbridge strives to provide all patients, regardless of their ethnicity, age and economic conditions, with accessible medical devices and services. Forward-Looking Statements This news release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements include statements regarding benefits of the strategic transaction with Zylox-Tonbridge, benefits to our manufacturing structure, the pathway for Avinger products to enter the Greater China market, benefits of accessing Zylox-Tonbridge's peripheral products, the potential expansion of the Peripheral Vascular Intervention product portfolio of Zylox-Tonbridge, potential benefits to patients of the collaboration with Zylox-Tonbridge, the improvement in our operating cost structure, the opportunities for new revenue growth and increased sales productivity, and obtaining stockholder approval to facilitate the equity financing. Such statements are based on current assumptions that involve risks and uncertainties that could cause actual outcomes and results to differ materially. These risks and uncertainties, many of which are beyond our control, include our dependency on a limited number of products; the resource requirements related to Pantheris, Tigereye and our Lightbox imaging console; the outcome of clinical trial results; the adoption of our products by physicians; our ability to obtain regulatory approvals for our products; as well as the other risks described in the section entitled "Risk Factors" and elsewhere in our Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 16, 2023, as amended, and Quarterly Reports on Form 10-Q. These forward-looking statements speak only as of the date hereof and should not be unduly relied upon. Avinger disclaims any obligation to update these forward- looking statements. Investor Contact: Matt Kreps Darrow Associates Investor Relations (214) 597-8200 mkreps@darrowir.com Public Relations Contact: Phil Preuss Chief Commercial Officer Avinger, Inc. (650) 241-7942 pr@avinger.com SOURCE: Avinger, Inc. View the original press release on accesswire.com

The accumulation of misfolded or damaged proteins in long-lived, non-dividing cells like neurons are linked to neurodegenerative diseases like Alzheimer's. A study now finds that the build-up of these toxic proteins also influences oocyte quality and female fertility. The researchers discovered that mouse oocytes have specialized structures which roam the cytoplasm and act like a clean-up crew which capture and hold onto protein aggregates, rendering them harmless. Failure to degrade the toxic proteins led to the formation of defective eggs. 3 in 5 (60%) of mouse embryos that inherited the toxic proteins failed to complete the very earlies stages of development. The study presents a new frontier to explore the underlying mechanisms of poor oocyte quality, which is the leading cause of female infertility. Oocytes are immature egg cells that develop in almost all female mammals before birth. The propagation of future generations depends on this finite reserve of cells surviving for many years without incurring damage. In mice, this can be a period of up to eighteen months, while in humans it can last almost half a century, the average time between birth and menopause. How the cells accomplish this remarkable feat of longevity has been a longstanding question. Researchers at the Centre for Genomic Regulation (CRG) in Barcelona have discovered a new mechanism which explains how oocytes remain in pristine conditions for decades without succumbing to the wear and tear that would cause other cell types to fail. The findings, reported today in the journal Cell, represent a new frontier to explore unexplained causes of infertility. The researchers looked at protein aggregates, which are clumps of misfolded or damaged proteins. If left unchecked, these harmful substances accumulate in the cytoplasm and have highly toxic effects. Protein aggregates are known to accumulate in neurons and their effects have been linked to several neurodegenerative diseases. Cells usually manage aggregates by breaking them down with specialized enzymes. They can also divide into two new cells, concentrating aggregates in one of the cells and sparing the other. But oocytes are not like the other cells. Their long life means they cannot dissipate toxic substances through cell division. Constantly breaking down protein aggregates is an inviable strategy, as it requires using a high amount of energy that may not be available. Oocytes also have the job of donating their entire cytoplasm to an embryo after fusing with a sperm, and so prefer to reduce their metabolic activity, a strategy which avoids generating by-products which can damage the maternal DNA and compromise future reproductive success. This makes oocytes particularly sensitive to the effects of misfolded or damaged proteins. However, "in contrast to the tens of thousands of papers on protein aggregation in neurons, how mammalian oocytes cope with protein aggregation is essentially unstudied, despite having the same problem of being long-lived and non-dividing," explains Dr. Elvan Böke, Group Leader of the Oocyte Biology & Cellular Dormancy programme at the Centre for Genomic Regulation and author of the study. "We wanted to explore how oocytes deal with these misfolded or damaged proteins," adds Dr. Böke. Patrolling 'clean-up crews' Dr. Böke's team, led by Dr. Gabriele Zaffagnini, started by collecting thousands of immature oocytes, mature eggs, and early embryos from adult mice. Using special dyes, they observed how the protein aggregates behave in real-time using a technique called live-cell imaging. They also used electron microscopy to get a closer look and see nanoscopic details inside cells, work that took five and a half years to complete. The researchers discovered special structures in the oocytes which they named EndoLysosomal Vesicular Assemblies -- or ELVAs for short. These structures -- there are about 50 per each oocyte -- roam the cytoplasm, where they capture and hold onto protein aggregates, rendering them harmless. Cells have many subcellular structures known as organelles, which perform jobs much like an organ does in the body. The researchers conceptualise ELVAs as a "superorganelle" because it is a network of many different types of cellular components working together as a single unit. The study revealed a crucial moment during the oocyte maturation stage, which is when an oocyte converts into a mature egg, preparing for ovulation and possible fertilisation. During this stage, the researchers observed ELVAs moving towards the cell's surface and breaking down the protein aggregates, essentially deep-cleaning the cytoplasm. This is the first observation of the unique strategy oocytes employ to get rid of protein aggregates. "An oocyte must donate all its cytoplasm to the embryo at fertilisation, so it cannot afford for garbage to accumulate, which would pose an existential risk for its function. In that sense, ELVAs are like a sophisticated waste disposal network or clean-up crew, patrolling the cytoplasm to ensure no aggregates are freely floating. ELVAs keep these aggregates in a confined environment until the oocyte is ready to dispose of them in one fell swoop. It's an effective and energy-efficient strategy," says Dr. Zaffagnini, postdoctoral researcher at the Centre for Genomic Regulation. Protein aggregates may contribute to infertility Fertility declines with age, and poor oocyte quality is the major cause of female infertility. Global infertility rates are also on the rise, with delayed motherhood being one of the contributing factors. Understanding how oocytes remain healthy, and what causes these strategies to fail with age, is critical for understanding unexplained causes of infertility and open up new avenues for treatment. The findings of the study suggest that the presence of protein aggregates could interfere with both egg and embryo quality. When the researchers experimentally prevented the ability of ELVAs to degrade protein aggregates during the oocyte maturation process, it led to the formation of defective eggs. When the researchers intervened and "forced" the embryos to inherit aggregated proteins, 3 in 5 (60%) failed to complete very early stages of development. "A lot of studies have historically focused on one small aspect of why oocyte quality declines, which are meiosis and euploidy. However, a recent review of eleven thousand embryo transfers has shown that the decline in female fertility with age are heavily influenced by other, yet unknown factors. Our research opens a fascinating future direction to explore whether protein degradation, and problems with how they are regulated in oocytes, could explain the age-related decline in embryo health," concludes Dr. Böke. Another type of long-lived cell which do not divide yet have to deal with protein aggregates are neurons. The accumulation of the harmful substances in these cells is linked to the development of several types of neurodegenerative diseases including Alzheimer's. Could ELVA-like compartments also exist in neurons and other cell types? The study opens the door for future research avenues beyond the field of reproduction.

Advanced multiple new products and achieved record fourth quarter U.S. T2Bacteria Panel salesLEXINGTON, Mass., Feb. 15, 2024 (GLOBE NEWSWIRE) -- T2 Biosystems, Inc. (NASDAQ:TTOO) (the “Company”), a leader in the rapid detection of sepsis-causing pathogens and antibiotic resistance genes, today announced preliminary unaudited financial and operational results for the fourth quarter and full year ended December 31, 2023. Full Year 2023 and Recent Commercial Highlights Achieved full year 2023 total revenue of $7.2 million, including sepsis and related product revenue of $6.8 million and research and contribution revenue of $0.4 million.Achieved fourth quarter 2023 total revenue of $1.7 million, comprised entirely of product revenue including record sales of the T2Bacteria Panel in the U.S.Executed contracts for 26 T2Dx® Instruments in 2023, including 19 T2Dx Instruments from outside the U.S. and 7 T2Dx Instruments from the U.S.Expanded international distribution network to include the Netherlands, Belgium, Vietnam, and the re-entry into Switzerland.Eliminated sepsis test backorder as of the end of January 2024. Recent Pipeline and Clinical Highlights Received FDA 510(k) clearance to add the detection of Acinetobacter baumannii to the FDA-cleared T2Bacteria Panel.Submitted a 510(k) premarket notification to the U.S. FDA to expand the use of the T2Candida Panel to include pediatric testing.Received Phase 2 award from the U.S. Department of Health and Human Services and the Steven & Alexandra Cohen Foundation’s LymeX Diagnostics Prize for the T2Lyme Panel.Advanced the T2Resistance Panel toward U.S. FDA 510(k) submission, expected to occur during the third quarter of 2024.Presented new clinical data at IDWeek 2023 demonstrating speed, accuracy, and clinical benefits of T2Dx Instrument, T2Bacteria Panel, T2Candida Panel, and T2Resistance Panel. Financial and Operational Updates Presented a detailed plan to Nasdaq Listing Qualifications Hearing Panel on February 15, 2024, to regain compliance with $35 million Market Value of Listed Securities requirement; response expected in the coming weeks.Executed agreement with CRG to convert an additional $15 million of the outstanding term loan into shares of common stock and shares of newly designated preferred stock (to the extent CRG’s beneficial ownership would be above 49.99% of the Company’s outstanding common stock), upon receipt of shareholder approval.Amended term loan agreement with CRG, extending the maturity date and interest-only period to December 31, 2025, and reducing the minimum cash covenant from $5.0 million to $500,000.Cash and cash equivalents totaled $15.7 million as of December 31, 2023. “We made considerable progress across the business during 2023, increasing our global installed base of T2Dx Instruments, generating record U.S. sales of our T2Bacteria Panel, strengthening our supply chain and manufacturing operations, advancing multiple new product development initiatives, and strengthening our balance sheet,” stated John Sperzel, Chairman and CEO of T2 Biosystems. “We are very excited by the progress on our new product pipeline, which includes the recent FDA clearances for the T2Biothreat Panel and the expanded T2Bacteria Panel to include the detection of Acinetobacter baumannii, as well as the pending FDA clearance to expand the T2Candida Panel to include pediatric testing. Additionally, we have three pipeline products that have received FDA Breakthrough Device designation, including the T2Resistance Panel, the T2Lyme Panel, and the Candida auris test. We believe we are well-positioned heading into 2024, and we expect to accelerate our product sales, enhance our operations, and continue to advance out new product pipeline.” 2024 Financial Outlook The Company expects full year 2024 total sepsis and related product revenue of $10.0 million to $11.0 million, representing growth of 49% to 64%, compared to $6.7 million in 2023. The Company’s 2024 revenue guidance consists entirely of sepsis and related product revenue and does not include potential sales of the T2Biothreat Panel or the T2Lyme Panel. Webcast and Conference Call InformationThe Company’s management team will host a conference call today, February 15, 2024, beginning at 4:30 pm ET. Investors interested in listening to the call may do so by dialing 888-506-0062 for domestic callers or 973-528-0011 for International callers and using conference ID 106354 approximately five minutes prior to the start time. A live and recorded webcast of the call will be available on the “Investors” section of the Company’s website at www.t2biosystems.com. About T2 BiosystemsT2 Biosystems, a leader in the rapid detection of sepsis-causing pathogens and antibiotic resistance genes, is dedicated to improving patient care and reducing the cost of care by helping clinicians effectively treat patients faster than ever before. T2 Biosystems’ products include the T2Dx® Instrument, the T2Bacteria® Panel, the T2Candida® Panel, the T2Resistance® Panel, and the T2Biothreat™ Panel, and are powered by the proprietary T2 Magnetic Resonance (T2MR®) technology. T2 Biosystems has an active pipeline of future products, including the U.S. T2Resistance Panel, the Candida auris test, and the T2Lyme™ Panel. For more information, please visit www.t2biosystems.com. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding our growth opportunities as a result of the receipt of FDA 510(k) clearance for the T2Biothreat Panel and 510(k) clearance to add Acinetobacter baumannii detection to the FDA-cleared T2Bacteria Panel, maintenance of our Nasdaq listing, our market opportunity, financial results, financial outlook, instrument contracts, timing of completing clinical trials and filing of an FDA submission, product demand, commitments or opportunities, and growth expectations or targets, as well as statements that include the words “expect,” “may,” “should,” “anticipate,” and similar statements of a future or forward-looking nature. The preliminary, estimated financial results for the fourth quarter and fiscal year ended 2023 contained in this press release contain forward-looking statements and are subject to the completion of management’s and the audit committee’s final reviews and our other financial closing procedures and are therefore subject to change. You should not place undue reliance on such preliminary information and estimates because they may prove to be materially inaccurate. The preliminary information and estimates have not been compiled or examined by our independent auditors and they are subject to revision as we prepare our financial statements as of and for the quarter ended December 31, 2023, including all disclosures required by U.S. generally accepted accounting principles. While we believe that such preliminary information and estimates are based on reasonable assumptions, actual results may vary, and such variations may be material. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, (i) any inability to (a) realize anticipated benefits from commitments, contracts or products; (b) successfully execute strategic priorities; (c) bring products to market; (d) expand product usage or adoption; (e) obtain customer testimonials; (f) accurately predict growth assumptions; (g) realize anticipated revenues; (h) incur expected levels of operating expenses; or (i) increase the number of high-risk patients at customer facilities; (ii) failure of early data to predict eventual outcomes; (iii) failure to make or obtain anticipated FDA filings or clearances within expected time frames or at all; or (iv) the factors discussed under Item 1A. “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2022, filed with the U.S. Securities and Exchange Commission, or SEC, on March 31, 2023, and other filings the Company makes with the SEC from time to time, including our Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While the Company may elect to update such forward-looking statements at some point in the future, unless required by law, it disclaims any obligation to do so, even if subsequent events cause its views to change. Thus, no one should assume that the Company’s silence over time means that actual events are bearing out as expressed or implied in such forward-looking statements. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this press release. Investor Contact:Philip Trip Taylor, Gilmartin Groupir@T2Biosystems.com 415-937-5406