Ibrexafungerp Citrate

Intravenous SCY-247 was generally well tolerated in healthy participants, with no drug-related serious adverse events Once-daily intravenous doses of 50 mg or higher achieved exposures at or above the target identified in murine models of invasive candidiasis Company expects to initiate Phase 2 development of SCY-247 in oral and IV formulations in 2027, subject to regulatory agreement SCY-247 development is advancing with the support of a BARDA contract providing up to approximately $214 million in non-dilutive funding if milestones are achieved JERSEY CITY, N.J., Oct. 22, 2026 (GLOBE NEWSWIRE) -- SCYNEXIS, Inc. (NASDAQ: SCYX) (“SCYNEXIS”, or the “Company”), a clinical-stage biotechnology company dedicated to advancing innovative solutions for severe rare diseases, today announced topline results from its Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) trial of the intravenous (IV) formulation of SCY-247, its second-generation triterpenoid (fungerp) antifungal candidate. SCY-247 is under development in both oral and intravenous (IV) formulations for the treatment and prevention of invasive fungal infections with the potential to provide therapeutic advantages by having activity against drug-resistant fungi. “With Phase 1 studies of both the intravenous and oral formulations of SCY-247 now complete, we can refine our plans for the next stage of development of this second-generation fungerp, designed to address the growing threat of antimicrobial resistance,” said Todd Minga, M.D., SVP of Research and Development at Scynexis. “Having both intravenous and oral formulations could provide flexibility in managing patients with invasive candidiasis and those at risk of invasive fungal diseases. We look forward to initiating a Phase 2 study next year, subject to agreement with the FDA." Recently, Scynexis was awarded a BARDA contract (75A50126C00007) providing up to approximately $214 million in non-dilutive funding, if milestones are achieved, to advance the development of SCY-247. The award is structured as a cost-share arrangement, with BARDA providing support for eligible SCY-247 costs. The Company expects to fund its share of near-term program costs for SCY-247 within its existing operating plan. The Company’s previously communicated development plans for SCY-770 to initiate a Phase 2 study in the fourth quarter of 2026 and the Company’s projected cash runway into 2029 remain unchanged. Phase 1 Study Results The study evaluated the safety and characterized the pharmacokinetics of intravenous SCY-247 to inform progression to, and dose selection for, a Phase 2 study in patients with invasive candidiasis. The Phase 1 study enrolled 56 healthy participants across seven cohorts: 42 received SCY-247 by peripheral intravenous infusion and 14 received placebo. The study evaluated single ascending doses up to 300 mg and multiple ascending doses administered once daily for seven days up to 200 mg. SCY-247 administered by peripheral intravenous infusion was generally well tolerated. The most commonly reported adverse reactions were mild to moderate erythema and pain at the infusion site. There were no drug-related serious adverse events or discontinuations due to a related adverse event. Intravenous doses of 50 mg once daily or higher achieved exposures at or above the efficacy target identified in murine models of invasive candidiasis (AUC 0–24 of 20 µg·h/mL). A previously completed Phase 1 study indicated that oral doses of 100 mg or higher are also anticipated to achieve the target exposure for efficacy. Overall, the safety, tolerability, and pharmacokinetic pro in this study support the continued clinical development of SCY-247. Further details of the results from this study will be presented at an upcoming scientific meeting. Invasive candidiasis is associated with high mortality, and resistance to the limited available antifungal options is making treatment increasingly challenging. Designed to address these limitations, SCY-247 has demonstrated in vitro and in vivo activity against several challenging Candida strains, including Candida auris , as well as most azole- and echinocandin-resistant strains. SCY-247 has been granted Orphan Drug, Qualified Infectious Disease Product (QIDP) and Fast Track designations by the U.S. Food and Drug Administration. Future activities for this project may be funded in whole or in part with federal funds from the U.S. Department of Health and Human Services (HHS); Administration for Strategic Preparedness and Response (ASPR); Center for the Biomedical Advanced Research and Development Authority (BARDA), under contract number 75A50126C00007. About SCY-247 SCY-247 is a second-generation triterpenoid (fungerp) antifungal candidate being developed for the treatment of invasive candidiasis and the prevention of invasive fungal diseases. As a member of a novel structural class, SCY-247 has a differentiated mechanism of action from existing antifungal classes and has demonstrated in vitro activity against a broad range of fungal pathogens, including strains resistant to currently available therapies. SCY-247 has been granted Orphan Drug, Qualified Infectious Disease Product (QIDP) and Fast Track designations by the U.S. Food and Drug Administration. Recently, Scynexis was awarded a BARDA contract (75A50126C00007) providing up to approximately $214 million in non-dilutive funding to advance the development of SCY-247. About SCYNEXIS SCYNEXIS, Inc. (NASDAQ: SCYX) is a clinical-stage biotechnology company dedicated to advancing innovative solutions for severe rare diseases. SCY-770 is being developed for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) and has been granted Orphan Drug designation. SCYNEXIS’s proprietary antifungal platform “fungerps” includes BREXAFEMME® (ibrexafungerp tablets), the first approved representative of this novel class, which has been licensed to GSK, and SCY-247, currently in clinical stages of development for the treatment and prevention of invasive fungal diseases. For more information, visit Forward-Looking Statements Statements contained in this press release regarding expected future events or results are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including but not limited to statements regarding: the Company’s expectation to initiate Phase 2 development of SCY-247 in oral and IV formulations in 2027, subject to regulatory agreement; the potential for SCY-247 to provide therapeutic advantages of both an oral and IV formulation; the amount and timing of any BARDA funding (under contract 75A50126C00007); the Company’s expectation to fund its share of near-term program costs for SCY-247 within its existing operating plan; the anticipated initiation of the SCY-770 Phase 2 study in Q4 of 2026; the statements concerning the Company’s cash runway into 2029, and other statements identified by words such as “will,” “potential,” “could,” “can,” “believe,” “intends,” “continue,” “plans,” “expects,” “anticipates,” “estimates,” “may,” other words of similar meaning or the use of future dates. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks inherent in regulatory and other costs in developing products, including the risk that SCYNEXIS may not reach alignment with the FDA on the planned Phase 2 study designs on the anticipated timelines or at all, and the risk that BARDA does not exercise one or more options under the BARDA contract (75A50126C00007). For the Company, this includes the future prospects of the Company’s SCY-247 and SCY-770 programs, the timing and results of the Company’s anticipated Phase 2 clinical studies, stock price volatility and uncertainties relating to the financial markets, the medical community and the global economy, and the impact of instability in general business and economic conditions, including changes in inflation and interest rates. These and other risks are described more fully in the Company’s filings with the Securities and Exchange Commission (the “SEC”), including without limitation, its most recent Annual Report on Form 10-K filed on March 4, 2026, including under the caption “Risk Factors,” and in other filings the Company makes with the SEC from time to time. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. CONTACT : Investor Relations John Fraunces LifeSci Advisors Tel: 917-355-2395 jfraunces@lifesciadvisors.com

综述目的：真菌感染的治疗仍是重大临床挑战。抗真菌研究领域的努力已促成若干创新疗法获批，并推动多种处于早期和晚期研发阶段的有前景药物取得进展。本综述对已获批或正在研发中的新型抗真菌药物进行最新概述，重点阐述其新特征及潜在临床影响。近期发现：三种新获批抗真菌药物已进入临床应用，引入了新的结构类别和给药优势，包括用于外阴阴道念珠菌病（vulvovaginal candidiasis, VVC）治疗的ibrexafungerp和oteseconazole，以及用于侵袭性念珠菌病（invasive candidiasis, IC）治疗的rezafungin。此外，五种新兴候选药物，包括fosmanogepix、olorofim、opelconazole、turletricin和encochleated amphotericin B，在口服生物利用度（oral bioavailability）、安全性（safety）和耐药谱（resistance profiles）方面代表重要进展。总结：这些进展共同标志着抗真菌治疗领域的关键性转变，为临床医生提供新机会，以优化治疗并改善严重且难以治疗的真菌感染患者的结局。引言（Introduction）真菌感染包括侵袭性和黏膜皮肤疾病，全球负担持续上升。侵袭性真菌感染（invasive fungal infections, IFIs）为系统性深部感染，可致命且病死率高。2019―2021年估计每年约650万例IFIs，导致380万例死亡，其中68%直接归因于IFIs；超过90%的IFIs死亡由Cryptococcus、Candida、Aspergillus、Histoplasma和Pneumocystis引起。同时，Candida auris及耐唑类Aspergillus等高耐药物种增加，部分对所有现有治疗耐药。IFIs研究不足，且气候变化可能扩大环境获得性真菌的地理范围。黏膜皮肤念珠菌病，尤其外阴阴道念珠菌病（vulvovaginal candidiasis, VVC）和复发性VVC（recurrent VVC, RVVC），也是重要公共卫生问题：VVC影响高达75%女性一生中至少一次，约5%―10%发生RVVC。当前治疗受限于抗菌谱、毒性、给药途径、药物相互作用（drug-drug interactions, DDI）、靶组织生物利用度和耐药性；多烯类、唑类和棘白菌素类三大类各有不足，因此亟需新型抗真菌药。已获批的新型抗真菌药（Novel Antifungals With Market Authorization）自2015年isavuconazole获批后，又有ibrexafungerp、rezafungin和oteseconazole获美国食品药品监督管理局（FDA）批准。1. Ibrexafungerp（Brexafemme，原SCY-078）Ibrexafungerp为首个三萜类抗真菌药，抑制葡聚糖合成酶，破坏真菌细胞壁完整性。其机制与棘白菌素抑制1,3 beta-D-葡聚糖（BDG）合成相似，但靶点重叠有限，故与棘白菌素交叉耐药有限。它是首个口服葡聚糖合成酶抑制剂。其对Candida和Aspergillus具有广谱活性，包括C. auris及携带FKS突变菌株、野生型和耐唑类Aspergillus，以及Cladosporium、Paecilomyces和Alternaria等；对Cryptococcus、Mucorales和Fusarium活性有限，并保留抗生物膜Candida活性。该药有静脉和口服剂型，目前口服剂型获批治疗VVC。口服后4―6 h达峰，中枢神经系统（central nervous system, CNS）穿透有限但组织分布广泛，溶解度呈pH依赖性，可在阴道组织和脓肿等酸性环境达高浓度；主要经CYP3A4肝代谢和胆汁排泄，半衰期20 h，肾功能不全无需调整剂量。常见不良反应为恶心、呕吐、腹泻和腹痛，动物研究提示胎儿毒性，妊娠期应避免。2021年基于VANISH 303和VANISH 306 III期试验获批治疗VVC；2022年基于CANDLE III期试验获批降低RVVC发生率。FURI、CARES和MARIO等III期试验分别评估其用于难治性真菌病、C. auris感染和侵袭性念珠菌病口服降阶梯治疗。第二代理三萜SCY-247处于早期开发阶段。2. Rezafungin（Rezzayo，原CD101）Rezafungin为第二代棘白菌素，是anidulafungin结构类似物，经胆碱基团修饰后半衰期显著延长，支持每周一次给药。其血药峰浓度和AUC呈线性、剂量比例增加，初剂后半衰期约80 h，第二剂后约150 h。口服生物利用度有限，仅静脉给药，方案为400 mg负荷剂量后200 mg每周一次。其代谢少，主要经粪便原型排泄，CYP450相互作用少，肾功能不全无需调整。常见不良反应包括肝功能异常、超敏反应和输注相关反应。其对大多数野生型和耐唑类Candida（包括C. auris）及Aspergillus（包括隐存种）有强活性；FKS突变株MIC升高，但活性与其他棘白菌素相当或略优。2023年获批治疗念珠菌血症和侵袭性念珠菌病，ReSTORE III期试验显示其第14天全局治愈率和30天全因死亡率非劣于caspofungin；ReSPECT III期试验在异基因造血干细胞移植（hematopoietic stem cell transplantation, HSCT）患者中预防IFIs达主要终点。其他研究涉及慢性肺曲霉病、肺孢子菌肺炎（Pneumocystis jirovecii pneumonia, PJP）、肝移植预防和儿科安全性。3. Oteseconazole（Vivjoa，原VT-1161）Oteseconazole为新型四唑类抗真菌药，通过替换三唑环提高对真菌羊毛甾醇14α-脱甲基酶（sterol 14α-demethylase CYP450）的选择性，减少对哺乳动物CYP450抑制，故药物相互作用风险较低。其对Candida（包括耐氟康唑的C. glabrata和C. krusei）活性更强，对Cryptococcus、Trichophyton、Coccidioides和Rhizopus arrhizus也有体外活性。需随餐服用，组织分布广并可穿透CNS，经人CYP酶代谢少，中位半衰期138天。方案包括单药方案和氟康唑诱导后oteseconazole维持方案。妊娠、哺乳及有生育潜力者禁用。2022年获批用于无生育潜力患者的RVVC；VIOLET III期试验显示其可显著减少培养确诊VVC至48周，UltraVIOLET显示维持治疗较氟康唑显著降低复发，严重VVC III期试验中治疗治愈率更高。在研新型抗真菌药（New Antifungals in the Pipeline）目前III期阶段最领先者为fosmanogepix、olorofim和opelconazole；turletricin已进入II期，encochleated amphotericin B曾进入II期但自2024年起开发暂停。1. Fosmanogepix（原APX001）Fosmanogepix为manogepix前药，选择性靶向真菌Gwt1，抑制糖基磷脂酰肌醇（glycosylphosphatidylinositol, GPI）锚定蛋白的翻译后修饰，影响细胞壁完整性。其对Aspergillus、Candida、Cryptococcus、Fusarium、Lomentospora prolificans、Scedosporium和双相真菌有活性，但对C. krusei无活性，对Mucorales活性可变。组织分布广泛，包括CNS和眼组织，口服和静脉生物利用度均>90%，药物相互作用少，无需实验室监测。II期研究在念珠菌血症和侵袭性霉菌感染中显示生存和临床成功概念验证。III期FAST-IC评估念珠菌血症和侵袭性念珠菌病，FORWARD-IM评估侵袭性霉菌感染。2. Olorofim（原F901318）Olorofim为首个orotomide类，选择性抑制真菌二氢乳清酸脱氢酶（dihydroorotate dehydrogenase, DHODH），干扰嘧啶合成。口服生物利用度>45%，组织分布良好并穿透CNS，经多种CYP450代谢但不诱导CYP450，药物相互作用风险低。其对Aspergillus、Fusarium、双相真菌及高度耐药的Lomentospora prolificans和Scedosporium有活性，但因DHODH远缘相关，对Candida、Cryptococcus和Mucorales无活性。IIb期FORMULA-OLS在治疗选择有限的侵袭性霉菌感染中临床成功率为75.2%，第42天全因死亡率11.9%。III期OASIS评估侵袭性曲霉病，已完成招募。3. Opelconazole（原PC945）Opelconazole为首个吸入给药的抗真菌药，属三唑类，抑制羊毛甾醇14a-demethylase。其主要在肺部起效，全身浓度低，毒性风险低，对酵母和霉菌（包括除A. niger外的Aspergillus、Candida和Mucorales）有活性。II期OPERA-S评估肺移植受者肺曲霉病预防，初步显示安全、耐受和有效；III期OPERA-T评估难治性侵袭性肺曲霉病，因中期分析显示opelconazole组有利应答率更低、死亡率更高而被申办方终止。4. Turletricin（EL219，原SF001）Turletricin为新型下一代多烯类，设计为长效、广谱、杀真菌并因增强麦角固醇选择性而降低肾毒性。其通过反转甲醇中心提高对真菌细胞选择性，保留麦角固醇提取而降低毒性。非临床研究显示对Candida、Cryptococcus、Aspergillus等广谱真菌有强效，但A. lentulus、A. calidoustus、A. terreus、双相霉菌、Fusarium和Mucorales敏感性降低。I期研究显示每周一次给药耐受良好且无肾毒性。FDA授予其QIDP和Fast Track。II期TREAT-1正在招募，比较EL219与标准治疗用于疑似侵袭性霉菌感染早期治疗。5. Encochleated amphotericin B（CAmB，原MAT2203）Encochleated amphotericin B通过结合固醇靶向真菌细胞膜，但采用固体磷脂双层包裹两性霉素B，避免胃肠道破坏，实现口服给药。其机制尚未完全明确，推测经吞噬和溶酶体融合后直接与真菌细胞膜作用，并保护机体免受两性霉素毒性。其为首个无肾或肝毒性限制的口服两性霉素制剂，初步资料显示组织分布广泛且无溶血毒性。EnACT I/II期在HIV相关隐球菌脑膜炎中显示高达95%生存率、毒性显著更低和脑脊液真菌清除良好；II期在耐唑类慢性黏膜皮肤念珠菌病中2周内显示临床疗效。III期ORALTO原计划评估侵袭性曲霉病，但2024年10月申办方终止合作谈判，试验时间不确定；目前仍可用于选择有限患者的同情用药。讨论（Discussion）Ibrexafungerp、rezafungin和oteseconazole获批是自isavuconazole以来抗真菌药物库的首次有意义扩展。三药中仅rezafungin获批治疗IFIs，即念珠菌血症和侵袭性念珠菌病；ibrexafungerp和oteseconazole仅获批VVC，但具更广潜力。Ibrexafungerp作为首个口服葡聚糖合成酶抑制剂，对耐药Candida有活性；oteseconazole增强真菌CYP51选择性、减少药物相互作用并延长复发抑制。二者均有致畸担忧，妊娠期禁用，而该人群VVC/RVVC常见，形成治疗缺口。Rezafungin因半衰期长、每周给药，是IFIs管理的重要进展。Fosmanogepix和olorofim为最有前景的候选药物，具新机制、良好安全性、口服和广泛组织穿透，并对高度耐药霉菌有活性。Turletricin保留广谱杀真菌活性并降低肾毒性，长效每周给药有利于门诊管理。Opelconazole和encochleated amphotericin B前景不确定，开发暂停凸显资金和后勤障碍。结论（Conclusion）抗真菌领域在长期创新有限后正迎来扩展。新型靶点、创新设计和改善的药代动力学可应对长期挑战，并扩大耐药和新兴病原体治疗选择、改善耐受性和可及性。但科学创新本身不足，持续投资、完成临床试验和合作对改善患者结局至关重要；随着真菌感染和耐药上升，保持抗真菌研发势头仍是关键优先事项。