Paromomycin Sulfate

Overwhelming shareholder support in favour of take-private transaction with Aditxt Studies presented at IDWeek 2024™ demonstrate ATI-1701 provides full protection against lethal tularemia in animal models after one year Alignment with U.S. Food and Drug Administration on development requirements for ATI-1801 NDA Submission HALIFAX, Nova Scotia, Nov. 14, 2024 (GLOBE NEWSWIRE) -- Appili Therapeutics Inc. (TSX:APLI; OTCPink: APLIF) (the “Company” or “Appili”), a biopharmaceutical company focused on drug development for infectious diseases and medical countermeasures, today announced its financial and operational results for the second quarter of its fiscal year 2025, which ended on September 30, 2024. All figures are stated in Canadian dollars unless otherwise stated. “During fiscal year 2025, Appili shareholders voted overwhelmingly in favor of the transaction with Aditxt, facilitating our access to capital and activating promising opportunities for Appili,” said Dr. Don Cilla, President and CEO of Appili. “The shareholder vote is an important milestone for Appili and brings us one step closer to ‘Making Promising Innovations Possible Together’ through Aditxt’s social incubator platform.” ATI-1701, Biodefense Vaccine Candidate with Strong U.S. Air Force Academy Funding Commitments ATI-1701, a novel live-attenuated vaccine for preventing F. tularensis, has previously secured US$14 million in awards from the United States Air Force Academy (“USAFA”). Under the cooperative agreement with USAFA, Appili manages a comprehensive development program, including nonclinical studies, CMC/manufacturing, clinical preparatory, and regulatory activities supporting an IND submission in 2025. Recent data presented by Appili's scientific team at the Military Health System Research Symposium and IDWeek 2024™ demonstrated strong efficacy results. Studies showed that a single dose of ATI-1701 provided full protection against lethal tularemia in animal models, with protection for one year after vaccination. Additional research highlighted the heightened risk of tularemia outbreaks in conflict zones and positioned ATI-1701 as a potentially valuable tool in protecting warfighters. Appili has recently had positive interactions with the United States Food and Drug Administration (“FDA”) in the form of a pre-IND meeting, confirming the development pathway for the majority of Appili’s proposed development plan. Appili is currently in the process of implementing suggested changes in its development effort. ATI-1801, Demonstrated safety and efficacy across multiple Phase 2 and Phase 3 studies ATI-1801, a novel topical formulation of paromomycin (15% w/w), is under advanced clinical development for treating cutaneous leishmaniasis, a disfiguring skin infection affecting hundreds of thousands globally. In a recent response to Appili’s Type B meeting request, the FDA agreed with the Company’s proposed strategy to establish a scientific bridge between previous clinical trial material and new drug product batches. The approach enables Appili to leverage key results from the clinical dossier for ATI-1801 licensed from U.S. Army Medical Materiel Development Activity, including the successful results of a Phase 3 study, and allows the completion of an New Drug Application much sooner than if additional clinical data were required. ATI-1801 has received Orphan Drug Designation from the FDA for certain forms of cutaneous leishmaniasis. The company is evaluating ATI-1801’s eligibility for a priority review voucher (“PRV”), which, if confirmed, would make it the second PRV-eligible program at Appili, alongside ATI-1701, which is potentially eligible for a PRV pending renewal of certain U.S. legislation. LIKMEZ™ (ATI-1501), FDA Approved Liquid Oral Reformulation of the Antibiotic Metronidazole In September 2023, Appili, together with its U.S. partner, Saptalis Pharmaceuticals LLC., announced the approval by the FDA of LIKMEZ™ (ATI-1501), LIKMEZ® is the first and only FDA-approved liquid formulation of metronidazole providing a novel prescribing option for patients with difficulty swallowing or experiencing taste-related hurdles. LIKMEZ, with patent coverage through 2039, addresses the unmet need in patients with dysphagia to avoid risks associated with drug compounding, and discontinuation related anti-microbial resistance. In November 2023, Saptalis, through a commercialization partner, launched LIKMEZ in the U.S. and the product is now available to patients and doctors. Appili earned milestone payments from Saptalis and is entitled to receive additional sales-based milestone payments and royalties from Saptalis based on sale of the product. Saptalis is currently in the process of identifying an alternative commercialization partner. Aditxt Arrangement On November 6, 2024, shareholders of the Company overwhelmingly voted in favour of a special resolution approving a plan of arrangement pursuant to which Aditxt Inc. (NASDAQ:ADTX) (“Aditxt”), through its wholly-owned subsidiary, Adivir, Inc. will acquire all of the issued and outstanding Class A common shares of the Company by way of a court-approved plan of arrangement under the Business Corporations Act (Ontario) (the “Transaction”). Approximately 29.50% of the outstanding Appili Shares were voted by shareholders and the Transaction was approved by 99.79% of the votes cast. For further details regarding the Transaction, please see Appili’s press release dated April 2, 2024 and Appili’s management information circular (the “Circular”) dated October 4, 2024, a copy of which is available under Appili’s profile on SEDAR+ (sedarplus.ca). Appili and Aditxt are in the process of satisfying the remaining closing conditions, which include: (1) the Company obtaining final court approval for the Transaction, and (2) Aditxt securing sufficient financing to complete the Transaction. Subject to satisfaction or waiver of the remaining closing conditions, Appili expects the Transaction to close in December 2024. Financial Results The Company prepares its financial statements in accordance with IFRS Accounting Standards as issued by the International Accounting Standard Board and Part I of Chartered Professional Accountants of Canada Handbook–Accounting. All figures are stated in Canadian dollars unless otherwise stated. The net loss and comprehensive loss of $0.8 million or $0.01 loss per share for the three months ended September 30, 2024, was $0.2 million lower than the net loss and comprehensive loss of $1 million or $0.01 loss per share during the three months ended September 30, 2023. This relates mainly to an increase in research and development expenses of $1 million, an increase in financing costs of $0.1 million and a decrease in revenue of $0.3 million. This increase was offset by a decrease in general and administrative expenses by $0.1 million, an increase in government assistance of $1.3 million, and an increase of $0.2 million in foreign exchange gain. As of September 30, 2024, the Company had cash of $0.7 million, compared to $0.1 million on March 31, 2024. As of November 13, 2024, the Company had 121,266,120 issued and outstanding Common Shares, 11,520,281 stock options, and 41,356,874 warrants outstanding. This press release should be read in conjunction with the Company’s unaudited interim condensed consolidated financial statements for the second quarter of the 2025 fiscal year and the related MD&A, copies of which are available under the Company’s profile on SEDAR+ at www.sedarplus.ca. About Appili TherapeuticsAppili Therapeutics is an infectious disease biopharmaceutical company that is purposefully built, portfolio-driven, and people-focused to fulfill its mission of solving life-threatening infections. By systematically identifying urgent infections with unmet needs, Appili’s goal is to strategically develop a pipeline of novel therapies to prevent deaths and improve lives. The Company is currently advancing a diverse range of anti-infectives, including an FDA approved ready-made suspension of metronidazole for the treatment of antimicrobial infections, a vaccine candidate to eliminate a serious biological weapon threat, and a topical antiparasitic for the treatment of a disfiguring disease. Led by a proven management team, Appili is at the epicenter of the global fight against infection. For more information, visit www.AppiliTherapeutics.com. Forward looking statementsThis news release contains “forward-looking statements”, including with respect to the funding commitment from USAFA and expected timing of invoice payment, advancing program towards IND, further anticipated milestones and the timing thereof, the Company’s development plans and timelines with respect to ATI-1501, ATI-1701 and ATI-1801, the timing of any milestone and/or royalty payments in respect of ATI-1501, consideration to be received by shareholders in connection with the proposed Transaction, the expected timing and process to complete the Transaction, and the Company’s expectations with respect to its ability to operate as a going concern and satisfy its ongoing working capital requirements. Wherever possible, words such as “may,” “would,” “could,” “should,” “will,” “anticipate,” “believe,” “plan,” “expect,” “intend,” “estimate,” “potential for” and similar expressions have been used to identify these forward-looking statements. These forward-looking statements reflect the current expectations of the Company’s management for future growth, results of operations, performance and business prospects and opportunities and involve significant known and unknown risks, uncertainties and assumptions, including, without limitation, those listed in (i) the annual information form of the Company dated June 25, 2024, (ii) the Cicular, and (iii) the other filings made by the Company with the Canadian securities regulatory authorities (which may be viewed at www.sedarplus.ca). Should one or more of these risks or uncertainties materialize or should assumptions underlying the forward-looking statements prove incorrect, actual results, performance or achievements may vary materially from those expressed or implied by the forward-looking statements contained in this news release. These factors should be considered carefully, and prospective investors should not place undue reliance on the forward-looking statements. The Company disclaims any intention or obligation to revise forward-looking statements whether as a result of new information, future developments or otherwise, except as required by law. All statements included in this press release relating to the Arrangement are qualified by reference to the “Forward Looking Statements” section included in the Arrangement Press Release. Media Contact:Jenna McNeil, Communications ManagerAppili Therapeutics E: JMcNeil@AppiliTherapeutics.com Investor Relations Contact:Don Cilla, President and CEOAppili TherapeuticsE: Info@AppiliTherapeutics.com

2023年，孟加拉国成为全球第一个获得世界卫生组织（WHO）消除内脏利什曼病认证的国家。而其他受该疾病严重影响的南亚和东非地区的国家也在朝着消除目标稳步前进——这部分归功于DNDi过去20年的研究工作帮助人们获得了更安全和更简单的治疗。当前， DNDi及其合作伙伴正专注于为内脏利什曼病患者提供全新的口服药物，从而支持全球实现和维持内脏利什曼病的消除。 //认识内脏利什曼病：现状与危害// 利什曼病（Leishmaniasis）可由20多种利什曼虫属原生动物寄生虫引起，目前已知有90多种白蛉可以传播这些利什曼虫属寄生虫。该病有三种主要形式：内脏利什曼病（Visceral leishmaniasis，VL）、皮肤利什曼病（Cutaneous leishmaniasis, CL）和皮肤粘膜利什曼病（Mucocutaneous leishmaniasis）。其中，内脏利什曼病（又名黑热病）是最严重的形式，它可能出现暴发并导致死亡，是继疟疾之后第二致命的寄生虫病。 据估计，全世界有6亿多人面临感染VL的风险，每年新发病例数在5万至9万之间，大约50%的VL患者为儿童群体。研究表明，大多数患者分布在巴西、东非和印度。而在中国，近年来病例报告主要集中于新疆、甘肃和四川等地。VL患者通常会出现发烧、体重下降、肝脾肿大等症状，如果不及时治疗，超过95%的患者会发生死亡。其中，携带艾滋病毒的VL患者尤其难以治愈，具有很高的复发率和死亡率。与其他人群相比，携带艾滋病毒的人群罹患VL的风险高出100倍以上。 [图源：DNDi] //推动进步：内脏利什曼病的治疗创新// 东非的VL患者迫切需要比现有标准治疗更安全、更简单的替代方案，特别是当地占比70%的儿童患者。2003年，DNDi创建了东非利什曼病平台（Leishmaniasis East Africa Platform，LEAP），来自20个机构的60名专家参与研究，并帮助推动了肯尼亚、埃塞俄比亚、乌干达和苏丹抗击VL的进展。 2018年，DNDi与AfriKADIA联盟合作在埃塞俄比亚、肯尼亚、苏丹和乌干达开展了一项III期临床研究，比较米替福辛和帕罗霉素（miltefosine and paromomycin，MF+PM）联合治疗与目前的标准治疗——硬葡萄糖酸钠和帕罗霉素（sodium stibogluconate and paromomycin，SSG+PM）的结局。研究结果显示，MF+PM与SSG+PM一样有效，但所需注射次数较少，治疗周期较短，没有SSG相关毒性风险，并且继发黑热病后皮肤利什曼病（Post-Kala-Azar Dermal Leishmaniasis，PKDL）的风险也更低。为确保MF+PM在儿科用药中的适当剂量，研究团队开展了进一步的工作，研究结果支持在儿童和成人患者中均实施较短的14天治疗方案。 [图源：DNDi] DNDi与第七届利什曼病世界大会和第28届LEAP平台会议的与会专家以及开展研究的区域和社区的利什曼病技术和咨询小组分享了试验结果。与此同时，世卫组织指南制定小组开始审查DNDi的 III期临床试验产生的证据，为东非地区成人和儿童VL患者的治疗指南的修订提供信息。 //打破传播链条：PKDL患者的治疗// 据报告，5-10%的VL患者会继发PKDL。该病症通常表现为面部、上臂和躯干部位出现斑点、丘疹或结节，还可能导致毁容和给患者造成极大的病耻感。此外，PKDL患者仍可以作为VL的传染源，因此，早期和有效的PKDL治疗对于持续减少VL传播至关重要。 基于此前完成的两项II期临床研究——在苏丹开展的旨在测试脂质体两性霉素B (LAmB)+MF和MF+PM的研究，以及在印度和孟加拉国开展的测试LAmB单药疗法和LAmB+MF组合疗法的研究，DNDi及其合作伙伴分别于2023年11月和2024年6月在期刊PLOS Neglected Tropical Diseases上发表了研究结果。由于这些新的科学证据，预计更短期、更安全的治疗方法将在未来被推荐给PKDL患者。 [图源：DNDi] //全新的口服药物：合作与创新// 2023年，DNDi与合作伙伴在开发新的分子实体方面取得了重大进展，这些实体有可能彻底改变VL的治疗方法，并支持其消除目标的实现。 LXE408是一种由DNDi与Novartis联合开发的首创新药化合物。2023年8月，印度的第二个研究点已经启动，并在当年招募了39名患者。与此同时，在埃塞俄比亚进行的一项类似的II期研究已于2024年4月入组了首位受试者。预计到2025年，这两项研究将总共招募140名参与者。 GSK245具有与LXE408相似的作用模式，由DNDi、GSK全球健康部门和邓迪大学药物发现部门合作开发。2023年，针对该化合物的研究继续进行，并完成了健康志愿者单次剂量递增的I期研究。 [图源：DNDi] 此外，DNDi及其合作伙伴也恢复了具有独特的作用机理的化合物DNDI-6899的开发。储存在药明康德的活性药物成分已完成重新加工和配制，以支持2024年启动的多次剂量递增I期研究。在上月举行的第43届DNDi科学咨询委员会会议上，DNDI-6899研发项目从40多个研发项目中脱颖而出，入选“2024年度项目”（2024 Projects of the Year），以表彰该项目在临床前研究中的突出进展。 在DNDi的所有利什曼病药物组合中，DNDI-6174提供了一种全新的作用模式，并且预期具有较低的人用剂量和有前景的安全边际。该化合物由DNDi与GSK和邓迪大学合作发现，并于2019年被提名为VL候选药物，该成果已于2023年12月发表在期刊Science Translational Medicine上。自2019年来，DNDi和Eisai一直在合作开发该化合物，并于2023年继续合作研究以扩大对该化合物非临床特征的了解，从而推进首次人体临床试验。 [图源：DNDi] 我们非常感激这一路同行的合作伙伴们，他们在为被忽视的患者群体推进医学创新方面发挥了重要作用。未来，我们将继续在利用现有药物提供更安全、更短周期的治疗的同时，完成全新药物的长期开发，以拯救生命，减少与内脏利什曼病有关的社会歧视和病耻感，并最终消除内脏利什曼病。 点击“阅读原文”，可了解更多DNDi为最被忽视的病人推动的医学创新。 关于DNDi 被忽视疾病药物研发倡议组织（DNDi）是一个以病患需求为出发点的非营利性药物研发组织。DNDi主要为被忽视的疾病患者研发新的治疗方法，其中包括昏睡病、南美锥虫病、利什曼病、淋巴丝虫病、足菌肿、儿童艾滋病/艾滋病以及丙型肝炎的治疗方法。DNDi同时也在协调ANTICOV临床试验，为非洲的轻度至中度新冠肺炎（COVID-19）患者寻找治疗方法。 自2003年成立以来，DNDi迄今已交付了13种全新的治疗方案，其中包括用于治疗利什曼病的新药物组合、两种固定剂量的抗疟药，首次成功研发的新化学实体药物非昔硝唑（fexinidazole）用于治疗昏睡病，以及通过南南合作研发的丙肝药物拉维达韦（ravidasvir），旨在为全球丙肝患者提供可负担的药物选择。 *点击下方图片，了解更多有关DNDi的介绍。