Glutaric Acidemia I

Regulated information – Inside information No bankruptcy filing Significant reduction in Working Capital costsAtlas commits to fund Oxurion’s Working Capital costs (including the Preclinical GA Program) through 2024 using the existing Atlas Funding Program, under the conditions as set out belowIntent to put in place Debt Restructuring planTwo new independent directors have been co-opted to the Board, and a new CEO/CFO, who will also act as an executive board member, have been appointed upon proposal of Atlas Leuven, BELGIUM – December 28, 2023 – 9:00 PM CET – Oxurion NV (Euronext Brussels: OXUR), a biopharmaceutical company headquartered in Leuven, announced today it has avoided bankruptcy by entering into a binding letter of intent (LOI) with Atlas Special Opportunities LLC (Atlas) and an addendum to the existing subscription agreement for convertible bonds with Atlas. Pursuant to these agreements, Atlas will continue to fund Oxurion under the existing EUR 20.8 million funding program with a focus on Oxurion’s preclinical programs and monetizing its other existing assets, potentially including both THR-149 and THR-687, while at the same time Oxurion is putting in place a debt restructuring plan with Oxurion’s creditors and seeking future corporate transactions or a business combination that would be complementary to debt restructuring, all of which remains uncertain. For the last five years, Oxurion’s preclinical program has been focused on developing innovative therapeutics to preserve the vision of elderly people suffering from Age-related Macular Degeneration (AMD) generally, and Geographic Atrophy (GA) specifically. GA is an advanced form of AMD and is the leading cause of blindness worldwide - GA is estimated to affect between 5-8 million people currently and is expected to increase at a rate of 7% annually. The market potential for GA is estimated at between USD 3-6 billion by 2028. Given this market potential, vast amounts of time and capital that have been invested to find an effective treatment for GA. Earlier this year the FDA approved the first medicine for the treatment of GA, SYFOVRE®1 (pegcetacoplan injection) from Apellis. SYFOVRE was shown in clinical trials to reduce the rate of GA lesion growth by no more than 36% with monthly IVT injections, with no significant improvement in vision, which leaves a tremendous unmet need for an effective treatment for GA. In August of this year, a second product was approved for GA, IZERVAY™2(avacincaptad pegol intravitreal solution) from Iveric Bio, an Astellas company, with a similar profile to SYFOVE. Prior to the approval of IZERVAY, Iveric Bio, whose principal asset was IZERVAY, was acquired by Astellas for USD 5.9 billion, demonstrating the significant value assets for treating GA can potentially generate. Both SYFOVRE and IZERVAY target a single pathway, the complement pathway. However, the causes of GA are multifactorial and Oxurion has developed a disease specific target discovery platform enabling it to study the disease from different angles in a rapid and capital efficient manner. Using the platform, Oxurion has already identified potential novel pathways involved in the pathogenesis of AMD/GA disease that have the potential to provide better treatment options for GA patients that are not focused solely on the complement pathway. The next step for Oxurion is to seek to validate these targets in various in vitro and in vivo models that the preclinical team has developed over the past years and that are representative of the disease characteristics of AMD/GA (patient in a dish). Oxurion’s approach potentially differentiates it from other methods through its unbiased target discovery approach and its multitargeting drug format, which the Company considers to be necessary to improve efficacy compared to the standard of care for such a multi-factorial disease. The Company expects that, if successful, its lead generation work could allow Composition of Matter patents to be filed in 2024, which would be the next value inflection point, after which the Company estimates it would take around two years and a further investment of approximately EUR 20 million in working capital before initiating a proof of concept study. Had the Company not been capital constrained, it would have undertaken these efforts previously. Atlas has now committed to fund the Company’s running costs including the GA program at least through 2024, provided the modified liquidity and market capitalization conditions set forth below are met, and to consider means of further monetizing both the Oncurious and Oxurion assets (potentially including THR-687 and THR-149), and in parallel to seek future corporate transactions or business combinations. To achieve these aims, the Company has agreed with the Chief Development Officer (CDO), the newly promoted Chief Scientific Officer (CSO), and the entire preclinical team to stay at the Company. The team consists of six world-class scientists with combined experience in researching retina diseases of more than 75 years, including 4 PhD’s/MDs. The team is led by Dr. Andy De Deene, CDO, who is a medical doctor with more than 15 years of retina drug development experience and led the development of Jetrea® which was approved in over 50 countries, and Philippe Barbeaux, CSO, a PhD with more than 15 years of preclinical experience in retina-related diseases. Andy and Philippe will both be members of the Executive Committee, together with the new acting CEO/CFO, Pascal Ghoson, who is a former M&A specialist at Rothschild bank and CFO of various listed companies on Euronext. Given that the Company will change its focus to preclinical development, the size of the Company will be reduced to approximately 10 persons, and the remainder of the Company’s personnel, including the current CEO/CFO Tom Graney, will participate in a voluntary redundancy program on terms that have been agreed, which will result in a cost saving of approximately 67% of its personnel cost going forward. Under the terms of the LOI, Atlas commits to pay EUR 500,000 to Kreos Capital VI (UK) Limited/Pontifax Medison Finance (Israel) L.P. and Pontifax Medison Finance (Cayman) L.P. (Kreos/Pontifax), and Kreos/Pontifax have agreed to remove the freeze on the Company’s bank accounts up to the same amount to pay certain costs related to December 2023. In addition, Atlas has committed to finance the additional funds required to cover the one-off expenses related to implementation of the LOI, for a total amount of EUR 355,000 (“LOI costs”). Atlas has also committed to funding the preclinical program through 2024 in monthly tranches of EUR 300,000 to be paid monthly starting in January 2024 through December 2024 (“Running costs”), provided that the conditions of the Atlas funding program, which are described below, are met (together the Running costs and the LOI costs are referred to as the “Working Capital costs”), allowing for Oxurion to stay in going concern, but not to exceed the remaining amount under the Atlas funding program, which is EUR 8.5 million. Atlas will not receive any commission fee in the context of the LOI. The Working Capital costs will be funded through the issuance of mandatory convertible bonds after the date of the LOI under the terms of the existing Atlas funding program. Atlas has agreed to waive liquidity and market capitalization conditions of the convertible bonds to fund the LOI Costs and the convertible bonds issued to set-off the EUR 500,000 reimbursement of Kreos/Pontifax. Subsequent tranches are subject to facilitated liquidity and market capitalization conditions (market cap at EUR 500,000 and total trading value of last 22 days above EUR 200,000). Atlas currently holds 296 convertible bonds in a total amount of EUR 7.4 million. Atlas formally commits not to convert Convertible Bonds issued after the LOI to pay the Working Capital costs and the LOI costs (the “New Convertible Bonds”) and to only convert old convertible bonds (i.e. convertible bonds issued in accordance with the Subscription Agreement and outstanding on the date of the second amendment to the funding program (the "Old Convertible Bonds")) having a combined EUR value equivalent to the New Convertible Bonds issued after the date of the LOI until the earlier date between (i) 12 months from the date of the LOI, (ii) the announcement by the Company of a potential partnership or transaction involving a third party or any major scientific update, or (iii) when the last rolling 22 trading days total volume of shares traded on the market is valued above EUR 1 million, in which case Atlas will be entitled to convert and trade shares in excess of the amount of New Convertible Bonds, but agrees not trade more than 30% of the total daily volume traded. The Atlas funding program is described further below and in section 13 (pp. 46 – 50) of the Prospectus dated March 29, 2023 (link), the supplements dated June 13, 2023 (link) August 22, 2023 (link), Section 1. (pp. 1 – 2) of the Third Supplement dated October 2, 2023 (link) and November 15, 2023 (link) (the “Prospectus”) and the Board reports dated March 7, 2023 (link) and respectively October 2, 2023 (link). Thomas Clay, Patrik De Haes and Tom Graney have stepped down from the Board as a condition of the LOI, and Charles Paris de Bollardière (former secretary of the Board of TotalEnergies), James Hartmann (former auditor at the U.S. Securities & Exchange Commission and Chief Compliance officer of various companies) have been co-opted as new independent directors and the new CEO/CFO, Pascal Ghoson, has been co-opted as a new executive director (the “New Board”). This press release is issued by the New Board. The primary driver underlying the Company’s communication last month that it was preparing to file for bankruptcy and that shareholders would likely not receive any value for their shares, was the right held by Kreos/Pontifax to enforce their security interest to freeze the Company’s liquid assets, which they did. That risk has been eliminated by Atlas successfully agreeing terms with Kreos/Pontifax to acquire their outstanding debt of around EUR 2.1 million for approximately EUR 1.6 million by entering into a binding agreement to purchase the debt along with assignment of the claim and related pledge, rights, interests, and security of Kreos/Pontifax, which shall be transferred to Atlas when Kreos/Pontifax is repaid, which is expected to occur on January 1, 2024, and until then, Kreos/Pontifax has agreed not to enforce their security interest. This repayment from Atlas to Kreos/Pontifax will not be dilutive to the shareholders. A comparable second rank security package shall cover any future New Convertible Bonds' subscriptions. Oxurion shall immediately partly reimburse the debt transferred from Kreos/Pontifax to Atlas with its own financial means and funds provided via New Convertible Bonds, and reduce the debt and the related pledge to around EUR 0.5 million by mid-January 2024. The conversion of mandatory convertible bonds under the existing funding program will significantly dilute existing shareholders, and to limit the amount of the dilution, while at the same time avoiding bankruptcy, as described above, Atlas has formally committed to limit its conversions of convertible bonds as described above. Concerning the amount of the dilution from the shares converted for the convertible bonds, while it is difficult to predict, the attached Annex to this press release attempts to project the possible dilution at a hypothetical conversion price of EUR 0.000460 to EUR 0.000092. For instance, the conversion of the Working Capital costs of EUR 4,950,000, could, at a hypothetical conversion price of EUR 0.000460 to EUR 0.000092, lead to the issuance of 10,761,000,000 to 53,805,000,000 new shares (depending on the conversion price), being a dilution of the voting rights of 75.51% to 93.91% and a financial dilution of 36.92% to 84.31% compared to the situation as of the date of this press release. Reference is made to the attached dilution table as Annex 1. In the event the total Working Capital costs would amount to the total remaining amount under the Atlas funding program, i.e. EUR 8.5 million, this could lead to the issuance of 18,479,000,000 to 92,392,000,000 new shares (depending on the conversion price), being a dilution of the voting rights of 84.12% to 96.36% and a financial dilution of 41.12% to 86.51% compared to the situation as of the date of this press release. Were Atlas to convert all EUR 7.4m in convertible bonds that they currently hold, together with the entire EUR 8.5m remaining under the Atlas Funding Program, at the hypothetical conversion prices set out above, and maintain ownership of all shares issued upon conversion, which is not its intent, this would result in Atlas holding more than 90% of Oxurion’s shares. However, given that Atlas intends to sell its shares issued upon conversion, it is highly unlikely that it would cross the threshold of 30% of the voting rights of Oxurion. In view of the extent of the dilution, any prospect of recovery for existing shareholders as far as share value is concerned is remote. At the same time, Oxurion is in the process of negotiating a debt restructuring plan with Oxurion’s larger creditors, which seeks their agreement to a significant reduction of their debt, combined with potential conversion to equity, payment delays and maturity extensions. The Company’s current debts amount to approximately EUR 15 million. The Company’s largest creditors are Atlas, Kreos/Pontifax and Syneos Healthcare. It is uncertain whether the Debt Restructuring will be successful, but were that to be the case, it is expected that the repayments will be financed by the Company issuing additional New Convertible Bonds to Atlas and potential debt for equity swaps (the “Debt Repayment”). While the amount of the Debt Repayment is being negotiated, the total amount of the New Convertible Bonds to be issued for the Working Capital Costs, LOI Costs, plus the Debt Repayments, shall not exceed the remaining funding available under the Atlas funding program as of the date of the LOI, which is EUR 8.5 million. Reference is made to the dilution table in Annex 1. Based on the foregoing, the Board has determined that the bankruptcy conditions are not met and the Company therefore will not file for bankruptcy as long that continues to be the case. About Oxurion Oxurion (Euronext Brussels: OXUR) is engaged in developing next-generation standard of care ophthalmic therapies for the treatment of retinal disease. Oxurion is based in Leuven, Belgium. More information is available at www.oxurion.com. Important information about forward-looking statements Certain statements in this press release may be considered “forward-looking”. Such forward-looking statements are based on current expectations, and, accordingly, entail and are influenced by various risks and uncertainties. The Company therefore cannot provide any assurance that such forward-looking statements will materialize and does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events, or any other reason. Additional information concerning risks and uncertainties affecting the business and other factors that could cause actual results to differ materially from any forward-looking statement is contained in the Company’s Annual Report. This press release does not constitute an offer or invitation for the sale or purchase of securities or assets of Oxurion in any jurisdiction. No securities of Oxurion may be offered or sold within the United States without registration under the U.S. Securities Act of 1933, as amended, or in compliance with an exemption therefrom, and in accordance with any applicable U.S. state securities laws. For further information please contact: Oxurion NVPascal GhosonChief Executive OfficerTel: +33 6 18 49 05 04pascal.ghoson@nessman-partners.com US Conway CommunicationsMary T. Conwaymtconway@conwaycommsir.com Annex: Dilution Table Dilution table 1 Registered trademark of Apellis Pharmaceuticals, Inc.2 Trademark of Iveric Bio, an Astellas company. Attachments EN NL

Researchers have identified the cause of an inherited metabolic disease common among people with Lumbee and other Native American heritage, overturning decades of settled science and pointing to new, more effective therapies. Duke Health researchers have identified the cause of an inherited metabolic disease common among people with Lumbee and other Native American heritage, overturning decades of settled science and pointing to new, more effective therapies. The finding, publishing online April 19 in the journal Science Translational Medicine, shatters the textbook explanations for how a type of protein breaks down in a child's brain, becoming toxic and leading to potentially fatal neurological problems. The inherited condition is called Glutaric Aciduria Type I (GA-1), and current literature describes the toxic substances as being produced in the brain instead of arising elsewhere and crossing the blood-brain barrier. Treatments for the condition, including a strict, low-protein diet, have limited success. Up to a third of children with the condition suffer long-term neurologic damage and some die. Because other metabolic disorders have been shown to break down proteins in the liver and then cause brain damage, the Duke researchers reopened the science into GA-1. The work was led by senior author Karl-Dimiter Bissig, M.D., Ph.D., an associate professor in Duke's departments of Pediatrics, Medicine, Biomedical Engineering and Pharmacology and Cancer Biology. Bissig and colleagues launched experiments in mice specially bred to have GA-1. They found that catabolites -- the residue left by the breakdown of an essential amino acid called lysine -- accumulate in the liver and do cross the blood-brain barrier. This leads to a toxic build-up of glutaric acid in the brain, causing nerve damage that impacts motor skills. The researchers were able to cure the condition in mice with either a liver transplant or CRISPR gene-editing technology. Other liver-targeted gene therapies might also be effective and could be administered once in a lifetime. "The original experiments led to the interpretation that the toxic catabolites were produced locally in the brain," Bissig said. "What our work demonstrates is the importance of challenging paradigms, particularly as new technologies and research approaches are available." Bissig said inadequate measures to address different mutations in specific populations are leading to health disparities. People with Native American, Amish and Irish heritage have high susceptibility to GA-1, which can be identified during newborn screenings; the genetic variant common in Lumbee populations seems to cause the most damaging disease. Because states decide what diseases are included in newborn screenings, GA-1 goes undiagnosed if it's not part of a state's chosen screening panel. Screenings could also be missed if babies are delivered at home. While early diagnosis and a low-protein diet have been lifesaving, the benefits are concentrated in Amish- and Irish-heritage children, who have historically had better access to health care services than Native Americans. "With a better understanding of this disease, we can now work to develop treatments that are more effective and easier to access," Bissig said. "It's much easier to treat the liver than the brain. We are now working to advance the more efficient and convenient therapies." In addition to Bissig, study authors include Mercedes Barzi, Collin G. Johnson, Tong Chen, Ramona M. Rodriguiz, Madeline Hemmingsen, Trevor J Gonzalez, Alan Rosales, James Beasley, Cheryl K. Peck, Yunhan Ma, Ashlee R. Stiles, Timothy C. Wood, Raquel Maeso-Diaz, Anna Mae Diehl, Sarah P. Young, Jeffrey I. Everitt, William C. Wetsel, William R. Lagor, Beatrice Bissig-Choisat, Aravind Asokan, and Areeg El-Gharbawy. The study received funding support from The Alice and Y. T. Chen Center for Genetics and Genomics; the National Institute of Diabetes and Digestive and Kidney Disease (DK115461, DK124477, T32DK060445); the National Heart Lung and Blood Institute (HL132840, R01HL089221); and the National Institute of General Medical Sciences (T32GM088129).

WALTHAM, Mass., April 16, 2021 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS), a global biopharmaceutical company and leader in targeted C3 therapies, today announced that 10 abstracts were accepted for presentation at the virtual Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting to be held May 1-7, 2021. These abstracts feature a breadth of data, from presentations that demonstrate the potential of AI to analyze the growth of GA lesions, to new safety and efficacy data for pegcetacoplan, an investigational targeted C3 therapy, in GA. “New imaging approaches, AI-based technologies, and ultimately the development of new medicines will transform the treatment of geographic atrophy,” said Federico Grossi, M.D., Ph.D., Chief Medical Officer of Apellis. “Our data across these disciplines at ARVO exemplify our leadership in the retina and underscore the potential of pegcetacoplan to become the first medicine for people living with GA, a relentless disabling disease.” The five oral presentations include studies that evaluated the use of AI to identify, monitor, and predict the growth of GA lesions. The analyses were performed on retinal scans from the positive Phase 2 FILLY study, which showed that pegcetacoplan reduced the growth rate of GA lesions, and were conducted in collaboration with the Ophthalmic Image Analysis (OPTIMA) group at the Medical University of Vienna, one of the world’s leading data analysis laboratories for retinal diseases. “Our collaboration showed that AI can distinctly and reliably measure GA disease progression,” said Ursula Schmidt-Erfurth, M.D., professor and chair of the Department of Ophthalmology at the University Eye Hospital, Vienna, Austria. “The results support the use of AI analytics as an ideal tool to evaluate disease activity as well as therapeutic efficacy in GA.”The oral presentations from the AI collaboration include: Apellis abstracts regarding the safety and efficacy of pegcetacoplan and unmet need in GA include: About OPTIMAThe Ophthalmic Image Analysis (OPTIMA) group at the Medical University of Vienna is a leading data analysis laboratory for retinal diseases. OPTIMA is a multidisciplinary group in retinology, computer science, and medical physics that develops computerized analysis methods for ophthalmic images and aims to individualize and lower treatment needs for patients affected by retinal diseases. About PegcetacoplanPegcetacoplan is an investigational, targeted C3 therapy designed to regulate excessive activation of the complement cascade, part of the body’s immune system, which can lead to the onset and progression of many serious diseases. Pegcetacoplan is a synthetic cyclic peptide conjugated to a polyethylene glycol polymer that binds specifically to C3 and C3b. Pegcetacoplan is being evaluated in several clinical studies across hematology, ophthalmology, nephrology, and neurology. Marketing applications for pegcetacoplan for paroxysmal nocturnal hemoglobinuria (PNH) are under review by the U.S. Food and Drug Administration (FDA), which has granted the application Priority Review designation, and the European Medicines Agency (EMA). Pegcetacoplan was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of geographic atrophy and received orphan drug designation for the treatment of C3G by the FDA and European Medicines Agency. For additional information regarding pegcetacoplan clinical trials, visit . About Geographic Atrophy (GA) GA is an advanced form of age-related macular degeneration (AMD), a leading cause of blindness. GA lesions affect the central portion of the retina, known as the macula, which is responsible for central vision. Excessive complement activation drives irreversible lesion growth in GA1, and C3 is the only target to precisely control complement overactivation. GA is progressive and irreversible, leading to central visual impairment and permanent loss of vision. Based on published studies, approximately one million people have GA in the United States and 5 million people have GA globally.2.3 There are currently no approved treatments for GA. About Apellis Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company that is committed to leveraging courageous science, creativity, and compassion to deliver life-changing therapies. Leaders in targeted C3 therapies, we aim to develop transformative therapies for a broad range of debilitating diseases that are driven by excessive activation of the complement cascade, including those within hematology, ophthalmology, nephrology, and neurology. For more information, please visit . Apellis Forward-Looking Statement Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the implications of preliminary clinical data. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether the company’s clinical trials will be fully enrolled and completed when anticipated; whether preliminary or interim results from a clinical trial will be predictive of the final results of the trial; whether results obtained in preclinical studies and clinical trials will be indicative of results that will be generated in future clinical trials; whether pegcetacoplan will successfully advance through the clinical trial process on a timely basis, or at all; whether the results of the company’s clinical trials will warrant regulatory submissions and whether pegcetacoplan will receive approval from the FDA or equivalent foreign regulatory agencies for GA, PNH, CAD, C3G, IC-MPGN, ALS or any other indication when expected or at all; whether, if Apellis’ products receive approval, they will be successfully distributed and marketed; and other factors discussed in the “Risk Factors” section of Apellis’ Annual Report on Form 10-K filed with the Securities and Exchange Commission on February 25, 2021 and the risks described in other filings that Apellis may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Apellis specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Contacts: ApellisMedia:Mark Dolemedia@apellis.com617.997.3484 Investors: Argot Partnersapellis@argotpartners.com212.600.1902 ____________________________________________ 1 Seddon, JM, Rosner, B. Validated prediction models for macular degeneration progression and predictors of visual acuity loss identify high-risk individuals. Am J Ophthalmol 2019;198:223–261. 2 Rudnicka AR, Jarrar Z, Wormald R, et al. Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta-analysis. Ophthalmology 2012;119:571–580. 3 Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2014;2:e106–116.