TNFRSF14

Acquired AVTX-009, Phase-2 ready anti-IL-1β mAb, in March 2024 Increased cash position with private placement financing in March 2024 providing up to $185 million, including initial upfront investment of $115.6 million Topline results from planned Phase 2 trial of AVTX-009 in hidradenitis suppurativa expected in 2026 Expected cash runway into 2027 WAYNE, Pa. and ROCKVILLE, Md., March 29, 2024 (GLOBE NEWSWIRE) -- Avalo Therapeutics, Inc. (Nasdaq: AVTX), today announced business updates and year-end financial results for 2023. “We are very excited about the acquisition of AVTX-009 and concurrent financing of up to $185 million, $115.6 million of which we received upfront. The progress we made in 2023 to strengthen our balance sheet helped enable these transactions. I am proud of the team’s efforts and continued dedication in executing our strategy focused on the treatment of inflammatory conditions,” said Dr. Garry Neil, Chief Executive Officer and Chairman of the Board. “Our focus in 2024 is executing operationally on the development of AVTX-009 for the treatment of hidradenitis suppurativa. Our experienced team is ready to hit the ground running on progressing the drug candidate and is motivated by the potential of developing a meaningful treatment for patients suffering from hidradenitis suppurativa, many of whom are searching for improved treatment options.” Corporate Updates On March 27, 2024, Avalo acquired AVTX-009, a Phase 2 ready anti-IL-1β mAb, through an acquisition of AlmataBio, Inc. The consideration included stock valued at $15 million, as well as a $7.5 million payment due upon closing of the private placement investment. Avalo is also required to pay development milestones to the former AlmataBio stockholders including $5 million due upon the first patient dosed in a Phase 2 trial in patients with hidradenitis suppurativa (HS) and $15 million due upon the first patient dosed in a Phase 3 trial, both of which are payable in cash, Avalo stock, or a combination thereof at the election of the former AlmataBio stockholders. On March 28, 2024, Avalo closed a private placement led by Commodore Capital and TCGX, with participation from BVF Partners, Deep Track Capital, OrbiMed, Petrichor, and RA Capital Management for gross proceeds of up to $185 million, including $115.6 million of initial upfront funding received at close. The upfront investment is expected to fund operations through Avalo’s planned Phase 2 data readout in hidradenitis suppurativa and into 2027. As part of the private placement, the Company issued (i) an aggregate of $115.6 million of non-voting convertible preferred stock and (ii) warrants to purchase Avalo’s common stock or an equivalent amount (as converted to common stock) of non-voting convertible preferred stock for an aggregate exercise price of $69.4 million. The warrants are exercisable for approximately $5.80 per underlying share of common stock until the earlier of five years from the date of issuance or 30 days after the public announcement of the first patient dosed in a Phase 2 trial of AVTX-009 in HS. On an as-converted basis and after accounting for the financing and acquisition (excluding the exercise of the warrants), the total number of shares of Avalo common stock outstanding would be approximately 23.4 million immediately after the closing of the transactions. Program Updates and Milestones: AVTX-009: Anti-IL-1β monoclonal antibody (mAb) targeting inflammatory diseases. Avalo intends to pursue the development of AVTX-009 in hidradenitis suppurativa and expects topline data from its planned Phase 2 trial in hidradenitis suppurativa in 2026. In addition to hidradenitis suppurativa, Avalo intends to develop AVTX-009 in at least one other chronic inflammatory indication. Quisovalimab (AVTX-002): Anti-LIGHT mAb targeting immune-inflammatory diseases. Avalo is conducting a strategic review of the quisovalimab program. AVTX-008: B and T Lymphocyte Attenuator (BTLA) agonist fusion protein targeting immune dysregulation disorders. Avalo is conducting a strategic review of the AVTX-008 program. 2023 Financial Update: As of December 31, 2023, Avalo had $7.4 million in cash and cash equivalents. We raised approximately $46.2 million of net proceeds from equity financings in 2023 and fully retired our original $35 million of debt with principal payments of $21.2 million, inclusive of the full payoff of the loan in September 2023. The decrease in net loss was primarily attributable to a $26.2 million decrease in operating expenses driven by significantly reduced research and development expenses and selling, general and administrative expenses partially offset by a decrease of $14.2 million in license and other revenue. The significant reduction of research and development expenses was driven by fewer development programs ongoing during 2023 (due to divestitures in both 2022 and 2023), the AVTX-002 trial reading out in June of 2023 with no new trials initiated in the second half of the year, and a reduction of manufacturing costs due to the timing of manufacturing runs. Selling, general and administrative expenses decreased due to a smaller infrastructure to support the focused pipeline, severance in 2022 that did not repeat, as well as cost savings initiatives. Net loss per share decreased as a result of the decrease in net loss and due to an increase in the shares outstanding. In March 2024, we closed a private placement financing for gross upfront proceeds of $115.6 million. Avalo estimates upfront net proceeds of approximately $105 million after deducting estimated transaction fees and expenses from both the private placement financing and the acquisition of AlmataBio. We expect future research and development expenses and cash used in operating activities to increase in 2024 as a result of our development plans to initiate and progress a Phase 2 trial in hidradenitis suppurativa. Topline results from this planned Phase 2 trial are expected in 2026 and the upfront funding is expected to fund operations through this data readout and into 2027. Consolidated Balance Sheets (In thousands, except share and per share data) December 31, 2023 2022 Assets Current assets: Cash and cash equivalents $ 7,415 $ 13,172 Other receivables 136 1,919 Inventory, net — 20 Prepaid expenses and other current assets 843 1,290 Restricted cash, current portion 1 15 Total current assets 8,395 16,416 Property and equipment, net 1,965 2,411 Goodwill 10,502 14,409 Restricted cash, net of current portion 131 131 Total assets $ 20,993 $ 33,367 Liabilities and stockholders’ equity Current liabilities: Accounts payable $ 446 $ 2,882 Deferred revenue — 88 Accrued expenses and other current liabilities 4,172 13,214 Notes payable, current — 5,930 Total current liabilities 4,618 22,114 Notes payable, non-current — 13,486 Royalty obligation 2,000 2,000 Deferred tax liability, net 155 141 Derivative liability 5,550 4,830 Other long-term liabilities 1,366 1,711 Total liabilities 13,689 44,282 Stockholders’ equity (deficit) : Common stock—$0.001 par value; 200,000,000 shares authorized at December 31, 2023 and 2022; 801,7461 and 39,2941 shares issued and outstanding at December 31, 2023 and 2022, respectively 1 — Additional paid-in capital1 342,437 292,909 Accumulated deficit (335,134 ) (303,824 ) Total stockholders’ equity (deficit) 7,304 (10,915 ) Total liabilities and stockholders’ equity (deficit) $ 20,993 $ 33,367 1Amounts for prior periods presented have been retroactively adjusted to reflect the 1-for-240 reverse stock split effected on December 28, 2023. The consolidated balance sheets as of December 31, 2023 and 2022 have been derived from the audited financial statements, but do not include all of the information and footnotes required by accounting principles accepted in the United States for complete financial statements. Consolidated Statements of Operations (In thousands, except per share data) Year Ended December 31, 2023 2022 Revenues: Product revenue, net $ 1,408 $ 3,364 License and other revenue 516 14,687 Total revenues, net 1,924 18,051 Operating expenses: Cost of product sales 1,284 3,434 Research and development 13,784 31,308 Selling, general and administrative 10,300 20,711 Goodwill impairment 3,907 — Amortization expense — 38 Total operating expenses 29,275 55,491 (27,351 ) (37,440 ) Other expense: Interest expense, net (3,417 ) (4,170 ) Change in fair value of derivative liability (720 ) — Other expense, net (42 ) (20 ) Total other expense, net (4,179 ) (4,190 ) Loss before income taxes (31,530 ) (41,630 ) Income tax expense 14 28 Net loss $ (31,544 ) $ (41,658 ) Net loss per share of common stock, basic and diluted1 $ (114 ) $ (1,063 ) 1 Amounts for prior periods presented have been retroactively adjusted to reflect the 1-for-240 reverse stock split effected on December 28, 2023. The consolidated statements of operations for the year ended December 31, 2023 and 2022 have been derived from the audited financial statements, but do not include all of the information and footnotes required by accounting principles generally accepted in the United States for complete financial statements. About AVTX-009 AVTX-009 is a humanized monoclonal antibody (IgG4) that binds to interleukin-1β (IL-1β) with high affinity and neutralizes its activity. IL-1β is a central driver in the inflammatory process. Overproduction or dysregulation of IL-1β is implicated in many autoimmune and inflammatory diseases. IL-1β is a major, validated target for therapeutic intervention. There is evidence that inhibition of IL-1β could be effective in hidradenitis suppurativa and a variety of inflammatory diseases in dermatology, gastroenterology, and rheumatology. About quisovalimab (AVTX-002) Quisovalimab is a fully human monoclonal antibody (mAb), directed against human LIGHT (Lymphotoxin-like, exhibits Inducible expression, and competes with Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator (HVEM), a receptor expressed by T lymphocytes). There is increasing evidence that the dysregulation of the LIGHT-signaling network which includes LIGHT, its receptors HVEM and LTβR and the downstream checkpoint BTLA, is a disease-driving mechanism in autoimmune and inflammatory reactions in barrier organs. Therefore, we believe reducing LIGHT levels can moderate immune dysregulation in many acute and chronic inflammatory disorders. Quisovalimab previously demonstrated proof of concept in COVID-19 induced acute respiratory distress syndrome including reduction in mortality and respiratory failure, as well as a positive signal in patients with Crohn’s Disease. About AVTX-008 AVTX-008 is a fully human B and T Lymphocyte Attenuator (BTLA) agonist fusion protein in the IND-enabling stage. AVTX-008 is differentiated by having specific binding to BTLA, with no binding to LIGHT or CD160. AVTX-008 also has high-serum stability and solubility. About Avalo Therapeutics Avalo Therapeutics is a clinical stage biotechnology company focused on the treatment of immune dysregulation. Avalo’s lead asset is AVTX-009, an anti-IL-1β mAb, targeting inflammatory diseases. Avalo’s pipeline also includes quisovalimab (anti-LIGHT mAb) and AVTX-008 (BTLA agonist fusion protein). For more information about Avalo, please visit . Forward-Looking Statements This press release may include forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts. Such forward-looking statements are subject to significant risks and uncertainties that are subject to change based on various factors (many of which are beyond Avalo’s control), which could cause actual results to differ from the forward-looking statements. Such statements may include, without limitation, statements with respect to Avalo’s plans, objectives, projections, expectations and intentions and other statements identified by words such as “projects,” “may,” “might,” “will,” “could,” “would,” “should,” “continue,” “seeks,” “aims,” “predicts,” “believes,” “expects,” “anticipates,” “estimates,” “intends,” “plans,” “potential,” or similar expressions (including their use in the negative), or by discussions of future matters such as: the intended use of the proceeds from the private placement; integration of AVTX-009 into our operations; drug development costs, timing of trial results and other risks, including reliance on investigators and enrollment of patients in clinical trials; reliance on key personnel; regulatory risks; general economic and market risks and uncertainties, including those caused by the war in Ukraine and the Middle East; and those other risks detailed in Avalo’s filings with the Securities and Exchange Commission, available at . Actual results may differ from those set forth in the forward-looking statements. Except as required by applicable law, Avalo expressly disclaims any obligations or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Avalo’s expectations with respect thereto or any change in events, conditions or circumstances on which any statement is based. For media and investor inquiries Christopher Sullivan, CFO Avalo Therapeutics, Inc. ir@avalotx.com 410-803-6793 or Chris Brinzey ICR Westwicke Chris.brinzey@westwicke.com 339-970-2843

01OX40/OX40L概述OX40/OX40L 相互作用在炎性疾病、自身免疫性疾病、肿瘤以及移植免疫的发生、发展中起非常重要的作用。近年来，此研究越来越受到国内外学者的关注。OX40又叫做CD134、ACT35、TNFRSF4，于1987年首次在激活的老鼠CD4+ T细胞上被发现，属于TNFR超家族的一员。OX40基因和其它几个TNFR家族的分子(TNFR2, 4-1BB, HVEM, CD30, GITR, DR3)成簇的排列在人的1号染色体上。OX40是一个由249个氨基酸组成的Ⅰ型跨膜糖蛋白，其中49个氨基酸在细胞质内，186个氨基酸在胞外区域。OX40包含了具有三个全半胱氨酸结构域（CRD）和一个部分C端CRD。图1.OX40结构展示，包含3个完整的CRD，一个残缺的CRDOX40主要在活化的CD4+ T细胞和CD8+ T细胞上表达，而在NK细胞和NKT细胞上的表达水平相对较低。OX40L也称为CD252、TNFSF4、CD134L或gp34,是OX40的配体。是一种II型糖蛋白，具有23个氨基酸的胞质尾巴和133个氨基酸的胞外结构域。作为TNF超家族的一员，它以三聚体的形式表达。OX40L主要表达于抗原呈递细胞（APCs），如B细胞和树突状细胞。与TNF家族的其他成员类似，OX40信号通过TNF受体相关因子(TRAF)进行转导。OX40 信号在体内通过TRAF2 和 TRAF5以及在体外通过TRAF1、TRAF3 和 TRAF5转导至 T 细胞。OX40和OX40L的表达受到多种因素的调控。图2.表达 OX40 / OX40L 的人类细胞OX40通过TCR、CD28/CD80、CD40/CD40L等信号在T细胞上诱导表达，并在T细胞激活后的48-72小时达到峰值。TCR信号传导可以启动多种细胞上OX40的表达，CD28和其他细胞因子可以进一步促进其在活化的T细胞上的表达。也有报道称，IL-2、IL-4和TNF可以增强或延长OX40的表达。IL-2、TNF-α和IFN-γ在非酒精性脂肪性肝炎动物模型的肝组织中高表达，但只有外源性IL-2刺激才能上调CD4+ T细胞上OX40的表达。OX40L主要在抗原递呈细胞（APCs）上表达，APC在接触抗原后的1-3天内可以检测到OX40L的表达。通过Toll样受体传递的CD40信号和炎症信号可诱导抗原提呈细胞（APCs）上OX40L的表达。IL-18、IFN-g、胸腺基质淋巴细胞生成素（TSLP）、前列腺素E2等因子也能促进OX40L的表达。除在活化B细胞、树突状细胞（DC）和巨噬细胞等专业APCs外，OX40L也在NK、肥大细胞及平滑肌细胞和血管内皮细胞上表达。02OX40/ OX40L信号通路OX40-OX40L信号通路的生物学作用是增强T细胞受体（TCR）对T细胞的激活信号。图3. OX40/OX40L 相互作用模型缩写：Th2（辅助性T细胞2）、NK（自然杀伤细胞）、TCR（T细胞受体）、MHC（主要组织相容性复合体）、APC（抗原提呈细胞）OX40L是三聚体，每个OX40L与三个OX40分子结合。OX40/OX40L信号可通过PI3K-PKB/AKT、活化T细胞核因子（nuclear factor of activated T cells，NFAT）和 NF-κB等途径启动下游系列信号途径。OX40/OX40L信号对这些途径的持续激活导致部分抗凋亡B淋巴细胞瘤-2 基因（B-cell lymphoma-2，Bcl-2）家族成员（如 Bcl-xL、Bcl-2 和 Bfl-1）及调节细胞分裂分子上调，从而介导细胞因子及T细胞活化和增殖。OX40/OX40L 存在逆向信号转导，其逆向信号可通过调节胞内游离钙离子水平参与内皮细胞中基质金属蛋白酶 9（matrix metalloprotein 9，MMP-9）表达调控 。此外，OX40/OX40L 的逆向信号则能促进 DCs成熟及B细胞活化，并促进生发中心（Ger-minal centers，GCs）形成和 DCs 分化成熟，使B细胞产生高效价抗体及抗体类别转换。图4.OX40下游信号通路吉满生物根据市场需求和研究现状，推出OX40/OX40L过表达稳定细胞系/抗体/蛋白相关产品及服务（详细数据见文末），可用于抗体筛选、表征、一致性评价, 充分满足药物研发的需求，助力抗体药物临床申报。（咨询吉满客服联系同微信：18916119826）03OX40与疾病治疗癌症OX40信号可以促进CD4和CD8T细胞的存活，维持BCL-XL、BCL-2和survivn等抗凋亡蛋白的表达，增强细胞因子的产生，如IL-2、IL-4、IL-5和IFN-γ，增强肿瘤特异性效应T细胞的免疫应答，并增强肿瘤特异性记忆T细胞的产生。尽管OX40的研究结果很有希望，但单药并不足以治疗所有癌症类型或所有患者。通过小鼠模型研究表明，抗OX40与其他单克隆抗体、化疗药物和细胞因子联合使用相比单药疗法显示出了更高的治疗效果，因此为临床开发提供了鼓舞人心的方向。自身免疫性疾病与炎症自身免疫性疾病是OX40的重要应用领域。OX40通过与与OX40L结合导致T细胞活化以及效应功能增强。OX40/OX40L阻断可改善自身抗原特异性T细胞反应并降低自身免疫性疾病中的免疫活性。因此，阻断 OX40/OX40L通路对于治疗自身免疫性疾病具有重要意义。临床试验和动物模型已经证明阻断OX40或OX40L可以对自身免疫性疾病起到治疗作用，包括EAE、SLE、RA、结肠炎、AEU、1型糖尿病、多发性硬化、移植物抗宿主病（GVHD）和炎症性肠病（IBD）。另外，OX40L通过激活OX40信号通路，促进Th2等辅助性T细胞的活化，从而促进炎症的发生。因此，OX40和OX40L也有望成为特应性皮炎（AD）等治疗的一个新靶点。04OX40相关药物进展目前欧美以及国内的相关药企均已涉足该靶点药物研究，全球范围内，其中已有多款药物进入临床阶段，最快的已经进入3期临床。​点击图片上滑查看更多rocatinlimab（AMG 451/KHK4083）中国药物临床试验登记与信息公示平台官网公示，安进（Amgen）启动了三项国际多中心3期临床试验，以评估rocatinlimab（AMG 451）不同治疗方案治疗中度至重度特应性皮炎（AD）成人和青少年受试者的有效性、安全性和耐受性。公开资料显示，rocatinlimab是一种创新的全人源化抗OX40单克隆抗体，安进通过与协和麒麟（Kyowa Kirin）达成一项高达12.5亿美元的合作，以共同开发和商业化该产品。 Amlitelimab2023年11月14日、12月25日，赛诺菲陆续在Clinicaltrials.gov网站上注册了OX40L抗体Amlitelimab治疗中至重度特应性皮炎的两项三期临床，于2024年上半年启动，分别计划入组420例患者，预计2025年9-10月完成。BGB-A445百济神州OX40抗体新药BGB-A445，启动临床二期，联合治疗招募PD-（L）1治疗失败的非小细胞肺癌患者。IBI3562023年12月25日，据CDE临床试验登记与信息公示平台，信达生物OX40L单抗 IBI356 启动临床，用于特应性皮炎。这是国内首款获批临床的OX40L单抗。IMG-0072023年8月21日，创想生物宣布了其产品OX40抑制性抗体 IMG-007的I 期研究的顶线结果。在这项研究中，IMG-007表现出良好的安全性，IMG-007组未见比安慰剂组更高比例的特别不良事件（除了无剂量相关性的一些孤立 COVID-19病例），没有受试者报告任何与治疗相关的不良事件。重要的是，未报告发热或寒战事件。IMG-007是一种人源化IgG1单克隆抗体，能特异性地结合OX40受体，并阻断OX40和OX40L之间的信号转导。因其Fc区经过了生物工程改造，具有更长半衰期并没有抗体依赖性细胞介导的细胞毒性(ADCC)效应，可以消除ADCC所导致的潜在安全风险。目前，使用OX40靶向药物的临床试验最大的挑战是它作为单药或与ICB联合使用时的安全性。OX40/OX40L新药研发纵然有很多艰难挑战，但也很难阻挡研发热情。近两年制药巨头纷纷布局OX40领域，期待未来能够有更多的优秀产品问世。吉满生物助力药物研发，自主设计并开发了一系列稳定表达OX40/OX40L细胞系以及一系列高特异性、高灵敏性OX40/OX40L单克隆抗体。除此之外，吉满生物还可提供高活性OX40/OX40L重组蛋白，涵盖多种不同的功能Domain以及多个种属的蛋白产品，可满足客户在动物免疫、抗体筛选以及表位鉴定等不同场景中的需求，所有产品均已通过严格的质量监测。数据展示（部分）01蛋白相关数据验证GM-83111RP：Human OX40L Protein; His Tag02功能细胞系生物活性验证GM-C30855 H_OX40 Reporter Cell Line03表达细胞系流式验证用心做好细胞，为更好的靶向药吉满生物科技（上海）有限公司，是位于上海浦东的一家以创新为驱动的工程化细胞系研发公司，基于自有的国内最大报告基因平台、慢病毒平台以及最迅速的药研网资讯平台。目前，已构建出700余株现货单克隆细胞系产品，覆盖ROR1/DLL3/SLC39A6/TROP2/BCMA/BDCA/TREM2……200余新药热门靶点，其中有100余靶点开发有对应luciferase reporter方法，更有国内独家/首家CCR8, BDCA, TREM2和GAPR等luciferase的assay平台。参考资料https://doi.org/10.2147/OTT.S214211https://doi.org/10.3389/fimmu.2021.670637doi：10.1615/critrevimmunol.v29.i3.10https://doi.org/10.1136/esmoopen-2019-000573doi:10.1016/j.molimm.2017.01.006

SHELTON, CT / ACCESSWIRE / November 15, 2023 / NanoViricides, Inc. (NYSE American:NNVC) (the "Company"), reports that it has filed its Quarterly Report on Form 10-Q for the fiscal first quarter ending September 30, 2023 with the Securities and Exchange Commission (SEC) on Tuesday, November 14, 2023. The report can be accessed at the SEC website at . Financial Status - Sufficient Funds to Conduct Clinical Trial We reported that, as of September 30, 2023, we had cash and cash equivalent current assets balance of approximately $6.97 Million. In addition, we reported approximately $8.3 Million in Intangible Assets and Property and Equipment (P&E) assets, net of depreciation and amortization from $14.7 Million in P&E assets before depreciation. The strong P&E assets are comprised of our cGMP-capable manufacturing and R&D facility in Shelton, CT. The total current liabilities were approximately $0.95 Million. In comparison, as of June 30, 2023, we had cash and cash equivalent current assets balance of approximately $8.15 Million, and additional approximately $8.1 Million in Property and Equipment (P&E) assets, net of depreciation and amortization, while the total current liabilities were approximately $0.41 Million. The net cash utilized in the three months from July 1, 2023 was approximately $1.17 Million. The cash expenditure is expected to increase as the clinical trials progress for NV-CoV-2, our lead drug candidate to treat SARS-CoV-2 infection that causes COVID. On October 27, 2023, TheraCour Pharma, Inc. ("TheraCour"), our largest shareholder and licensor of our technology, exercised its right to convert the principal of the July 19, 2023 $1,500,000 convertible promissory note into 331,859 shares of the Company's Series A preferred stock and forgave and cancelled all of the accrued interest on the note. On November 8, 2023, the Company's President and CEO, Dr. Anil R. Diwan, agreed to provide a standby Line of Credit to the Company in the maximum amount of $2,000,000. The Company does not anticipate any borrowings under the Line of Credit during the current fiscal year. These actions have significantly improved the near-term liquidity outlook. NanoViricides Platform Technology and Drug Pipeline We have several drugs in our pipeline. Our lead clinical stage drug is NV-CoV-2 for the treatment of COVID and potentially the residual virus cases of "long COVID". It is in Phase 1a/1b human clinical trials in India sponsored by our licensee and collaborator, Karveer Meditech Pvt. Ltd. NV-387, our broad-spectrum antiviral nanoviricide agent, is the active ingredient in NV-CoV-2. It has demonstrated significantly superior effectiveness compared to remdesivir, an approved COVID drug, in an animal model of lethal hCoV-NL63 infection that simulates severe COVID-19 with lung disease. We have found that NV-387 is also effective against RSV infection in an animal model, matching the effectiveness of the last-resort toxic drug ribavirin. Additionally, subsequent to the quarterly reporting period, yesterday we reported that NV-387 was found to be as effective as the approved drug tecovirimat (TPOXX®, SIGA) in an animal model that is used for drug development for Smallpox and Mpox infections. While COVID pandemic is waning with a decreased severity from SARS-CoV-2 infections, "long COVID" cases continue and the potential of a more pathogenic variant arising cannot be overstated. In addition, due to the significant limitations of available therapeutics (namely Paxlovid®, Pfizer, and Veklury®, Gilead) there is a continuing need for a safe and effective COVID therapeutic that can be used in all patient populations. A safe and effective antiviral drug with such an extensive broad-spectrum activity across virus families as presented by NV-387 is an unmet medical need. This development is akin to the development of antibiotics to treat bacterial infections and could be as revolutionary towards the treatment of viral infections. The market size for COVID drugs is expected to continue to be in the billions of dollars range. The market size of an RSV therapeutic is estimated to be several billions of dollars. Although smallpox therapeutics are limited to government stockpiling, the market size for an effective smallpox therapeutic is estimated to be in the order of several hundred million dollars a year. We believe that upon completion of the Phase 1a/1b human clinical trials of NV-CoV-2, the NV-387 oral formulations may be eligible for Phase II/III clinical trials for RSV. There is no therapeutic available for RSV other than the last resort option of Ribavirin. We anticipate that NV-387 formulations would be expected to be eligible for the development of Poxvirus therapeutics under the FDA "Animal Rule," if further studies are successful. The Animal Rule regulatory pathway requires GLP studies in specific animal poxvirus infection models as replacement of the Phase II/III human clinical trials, and expanded Phase I human clinical trials to elucidate safety of the drug in human use. We plan to seek non-dilutive government funding for this indication. NV-387 has such broad-spectrum activity because it is designed to mimic the attachment receptors to which over 90% of viruses bind before infecting a cell. We are currently engaged in expanding the spectrum of activity of NV-387. NV-387 is an example of NanoViricides Platform Modality #1 implementation. NanoViricides Platform Technology has an important advantage in that no matter how much a virus changes in the field, it is unlikely to escape the nanoviricide drug because it is designed to mimic the very features that the virus uses to bind to and enter cells. These specific molecular signature features on the cellular side do not change even as the virus mutates, and nanoviricides are designed to mimic these features. In contrast, viruses readily escape antibodies as drugs, as well as vaccine-induced immunity as they evolve in the field, as is well known from the COVID-19 pandemic as well as Influenza pandemics and the continuing HIV/AIDS pandemic. A safe and effective antiviral drug that the virus would not escape by simple mutations or field evolution is the holy grail of antiviral drug development. We believe that the NanoViricides Platform technology meets this challenge. We have previously developed NV-HHV-1 as a skin cream formulation for the treatment of Shingles rash caused by the Varicella Zoster Virus (VZV) that also causes Chickenpox in children and immune-compromised adults. We plan on advancing NV-HHV-1 into clinical trials after advancing the NV-387 based drug programs into clinical trials. This drug mimics HVEM, a receptor used by herpesviruses. We plan on further development of our other drugs in the HerpeCide Program as we begin to advance NV-HHV-1 further into regulatory pathway. Further details of the NanoViricides Platform Technology, the various Modalities of its implementation, and the extensive drug candidate developments that we have undertaken, have been discussed in our Annual Report filed with the SEC on October 13, 2023. About NanoViricides NanoViricides, Inc. (the "Company") ( ) is a development stage company that is creating special purpose nanomaterials for antiviral therapy. The Company's novel nanoviricide® class of drug candidates are designed to specifically attack enveloped virus particles and to dismantle them. Our lead drug candidate is NV-CoV-2 for the treatment of COVID-19 disease caused by SARS-CoV-2 coronavirus. Our other advanced candidate is NV-HHV-1 for the treatment of Shingles (previously referred to as NV-HHV-101). The Company cannot project an exact date for filing an IND for any of its drugs because of dependence on a number of external collaborators and consultants. The Company is currently focused on advancing NV-CoV-2 into Phase I/II human clinical trials. NV-CoV-2 is our nanoviricide drug candidate for COVID-19 that does not encapsulate remdesivir. NV-CoV-2-R is our other drug candidate for COVID-19 that is made up of NV-CoV-2 with remdesivir encapsulated within its polymeric micelles. The Company believes that since remdesivir is already US FDA approved, our drug candidate encapsulating remdesivir is likely to be an approvable drug, if safety is comparable. Remdesivir is developed by Gilead. The Company has developed both of its own drug candidates NV-CoV-2 and NV-CoV-2-R independently. The Company is also developing drugs against a number of viral diseases including oral and genital Herpes, viral diseases of the eye including EKC and herpes keratitis, H1N1 swine flu, H5N1 bird flu, seasonal Influenza, HIV, Hepatitis C, Rabies, Dengue fever, and Ebola virus, among others. NanoViricides' platform technology and programs are based on the TheraCour® nanomedicine technology of TheraCour, which TheraCour licenses from AllExcel. NanoViricides holds a worldwide exclusive perpetual license to this technology for several drugs with specific targeting mechanisms in perpetuity for the treatment of the following human viral diseases: Human Immunodeficiency Virus (HIV/AIDS), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Rabies, Herpes Simplex Virus (HSV-1 and HSV-2), Varicella-Zoster Virus (VZV), Influenza and Asian Bird Flu Virus, Dengue viruses, Japanese Encephalitis virus, West Nile Virus, Ebola/Marburg viruses, and certain Coronaviruses. The Company intends to obtain a license for poxviruses and/or enteroviruses if the initial research is successful. The Company's technology is based on broad, exclusive, sub-licensable, field licenses to drugs developed in these areas from TheraCour Pharma, Inc. The Company's business model is based on licensing technology from TheraCour Pharma Inc. for specific application verticals of specific viruses, as established at its foundation in 2005. As is customary, the Company must state the risk factor that the path to typical drug development of any pharmaceutical product is extremely lengthy and requires substantial capital. As with any drug development efforts by any company, there can be no assurance at this time that any of the Company's pharmaceutical candidates would show sufficient effectiveness and safety for human clinical development. Further, there can be no assurance at this time that successful results against coronavirus in our lab will lead to successful clinical trials or a successful pharmaceutical product. This press release contains forward-looking statements that reflect the Company's current expectation regarding future events. Actual events could differ materially and substantially from those projected herein and depend on a number of factors. Certain statements in this release, and other written or oral statements made by NanoViricides, Inc. are "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. You should not place undue reliance on forward-looking statements since they involve known and unknown risks, uncertainties and other factors which are, in some cases, beyond the Company's control and which could, and likely will, materially affect actual results, levels of activity, performance or achievements. The Company assumes no obligation to publicly update or revise these forward-looking statements for any reason, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future. Important factors that could cause actual results to differ materially from the company's expectations include, but are not limited to, those factors that are disclosed under the heading "Risk Factors" and elsewhere in documents filed by the company from time to time with the United States Securities and Exchange Commission and other regulatory authorities. Although it is not possible to predict or identify all such factors, they may include the following: demonstration and proof of principle in preclinical trials that a nanoviricide is safe and effective; successful development of our product candidates; our ability to seek and obtain regulatory approvals, including with respect to the indications we are seeking; the successful commercialization of our product candidates; and market acceptance of our products. FDA refers to US Food and Drug Administration. IND application refers to "Investigational New Drug" application. cGMP refers to current Good Manufacturing Practices. CMC refers to "Chemistry, Manufacture, and Controls". CHMP refers to the Committee for Medicinal Products for Human Use, which is the European Medicines Agency's (EMA) committee responsible for human medicines. API stands for "Active Pharmaceutical Ingredient". (1. Cagno V, Tseligka ED, Jones ST, Tapparel C. Heparan Sulfate Proteoglycans and Viral Attachment: True Receptors or Adaptation Bias? Viruses. 2019 Jul 1;11(7):596. doi: 10.3390/v11070596. PMID: 31266258; PMCID: PMC6669472.) Contact: NanoViricides, Inc. info@nanoviricides.com Public Relations Contact: MJ Clyburn TraDigital IR clyburn@tradigitalir.com SOURCE: NanoViricides, Inc. View source version on accesswire.com: