THR-149

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

关注并星标CPHI制药在线          11月22日，据Fierce Pharma报道，微生物疗法公司Evelo Biosciences（后简称Evelo）决定解散，并将所有现金交给债权人，目前公司股价不到1美元（峰值曾逼近400美元）。公司在备案文件中称，解散这一决定，符合公司及其债权人、股东的"最佳利益"。       Evelo成立于2015年，公司业务聚焦于"小众"领域：通过肠道菌群作用来开发具有消炎作用的微生物疗法。Evelo致力于通过开发一种新型药物--单克隆微生物来改善全球患者的生活。Evelo希望能够以小肠为突破口，破解微生物组与人类免疫系统之间的相互作用机理。       值得一提的是，Evelo由知名风投机构Flagship孵化，其最为人熟知的案例是成功孵化Moderna。Flagship于1999年成立，目前已发起和孵化了大约100家创新公司，涉及生物制药领域、信息科技领域、农业领域和能源领域等，申请数千项专利和开发50多个临床项目。与绝大多数风投机构需要找标的不同，Flagship实现了制度化创业，采取内部孵化+投资的方式。历经24年发展，借力于"制度化创业"的理念，Flagship在创投圈极具独特性与标杆性。       在Flagship的背书下，Evelo成立短短四年时间，便于2018年5月完成IPO，募资8500万美元，吸引了谷歌风投、Celgene、Mayo Clinic等机构青睐。       作为一个通过研究微生物免疫疗法，来治疗癌症、自身免疫和炎性疾病的公司，Evelo基于自身平台布局了10条管线的研发，主要分为癌症和炎症性疾病两大领域。其中用于治疗炎症性疾病的EDP1867、EDP1815、EDP2939进度领先，曾被寄予厚望。       然而，这三款关键候选药物都折戟于临床试验。2022年4月，EDP1867治疗特应性皮炎的I期数据，由于未能有明显疗效，公司宣布停止EDP1867的研究。       今年2月，另一种特应性皮炎候选药物EDP1815在II期临床试验中失败。试验数据显示，在队列1、2和3中，分别有41%、38%和32%的EDP1815组患者在第16周实现EASI-50及以上应答。而安慰剂组有56%的患者达成EASI-50，数据碾压EDP1815。而且在后续更新的数据中，EDP1815依然失败。至此，其临床研究终止。       今年10月，EDP2939治疗银屑病的Ⅱ期临床试验依然失败。在一次次的临床试验失败后，Evelo公司的股价也一落千丈，从巅峰时期的398美元/股，现在仅剩0.6美元/股。       失去了投资者信任的Evelo，为了活下去，不得不削减管线、大规模裁员、调整管理层及寻求出售，最终在现金流耗尽后，不得不宣布解散。       事实上，Evelo是Flagship孵化公司中今年倒闭的第三家。今年早些时候，由Flagship孵化的Rubuis及Codiak BioSciences公司均宣告破产。       Rubuis的核心技术是"红细胞疗法"，公司希望通过其专有的RED平台，改造红细胞来表达治疗性蛋白质，之后对细胞进行增殖，并定向分化为无核细胞，从而治疗疾病。虽然从理论上看红细胞疗法或将是一款大有可为的疗法，但最终Rubuis还是倒在了临床试验阶段。其核心管线苯丙酮尿症药物RTX-134及实体瘤候选药物RTX-240均有效性不足，最终Rubuis走向陨落。       新药疗效不足，眼科Biotech走向衰亡       在临床验证阶段折戟的不仅仅有Flagship孵化的公司，在11月20日，据Fierce Pharma报道，眼科疗法Biotech公司Oxurion宣布，其眼科新药THR-149的II期临床失败，由于资金原因，公司准备申请破产。Oxurion成立于1991年，是一家比利时生物制药公司，2006年在布鲁塞尔泛欧交易所上市。       THR-149是Oxurion目前唯一一款在研的眼科产品，这是一款基于双环多肽的新型血浆激肽释放酶（PKal）抑制剂。血浆激肽释放酶是人体机体炎症反应的一个重要组成部分，如果过量可导致血管通透性增加、水肿和炎症。通过抑制激肽释放酶激肽系统（KKS），THR-149可防止视网膜血管通透性，神经变性和炎症的诱导。已有研究表明，PKal的激活会在糖尿病黄斑水肿（DME）患者中提高视网膜血管渗透性，以及微血管瘤和炎症的发生。       DME目前的标准疗法为拜耳/再生元的抗血管内皮 生长因子（anti-VEGF） 药物阿柏西普（Eyelea），不过并非所有DME患者的VEGF水平都升高，阿柏西普等仅对约40%~50%的患者效果欠佳。       THR-149被认为是抗VEGF治疗效果欠佳的DME患者的潜在治疗药物。为了验证这一想法，THR-149开展了名为KALAHARI的临床试验。这是一项由两部分组成的随机、前瞻性、多中心试验，旨在评估THR-149作为DME患者的潜在治疗方法。       在KALAHARI试验A部分中，所有剂量水平的THR-149都具有良好的安全性，所有不良事件强度均为轻至中度，未报告炎症以及严重的眼部不良事件。接受最高剂量THR-6的8例患者在第3个月（主要终点）实现了6.1个字母的平均最 佳矫正视力（BCVA）增益。       但是在试验B部分中，以Eyelea作为对照组后，THR-149视力改善程度不及Eyelea。第3个月时，THR-149组的最 佳矫正视力 (BCVA) 相对于基线的平均变化为-0.2个字母，Eylea的平均变化为+3.5个字母。       尽管在A部分试验中，THR-149展现出了良好的安全性和耐受性，但基于失败的B部分结果，并考虑到公司的现金状况，Oxurion做出了考虑申请破产的决定。截至今年6月底，Oxurion拥有220万欧元现金及等价物。       纵观以上破产倒闭的企业，均是核心管线遭遇临床试验失败，一步步走向深渊。可见对于Biotech来说，临床失败或许就意味着灭顶之灾。纵然创新科学研究需要经历不断的挫败与经验积累方能成就辉煌。但同时要明白及时止损也很重要。       参考来源：       1. Oxurion fails phase 2 eye disease trial, plans bankruptcy filing (fiercebiotech.com).     2. https://www.fiercebiotech.com/biotech/another-oxurion-eye-disease-drug-flunks-phase-2-leaving-biotech-all-last-prospect.       3. Flagship-Founded Microbiome Company Evelo Biosciences Throws in the Towel|BioSpace.       4. Flagship-founded Evelo Biosciences will dissolve after finding no 'viable alternative'-Endpoints News (endpts.com).智药研习会12月线上课程报名金笔奖征文进行中，速来投稿参与！来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~