Mometasone Furoate

ENLIGHTEN 2 trial met primary endpoint with LYR-210 demonstrating statistically significant improvement in the composite of the three cardinal symptoms (3CS) of CRS at 24 weeks (p=0.0078) ENLIGHTEN 2 trial also showed statistically significant improvement in key secondary endpoints in the full population of 3CS at 24 weeks (p=0.0209) and SNOT-22 score at 24 weeks (p=0.0101) Additionally, in pooled data from ENLIGHTEN 2 and ENLIGHTEN 1 trials in 64 CRS patients with nasal polyps, LYR-210 demonstrated a consistent positive trend over 24 weeks in multiple key efficacy endpoints Lyra plans to review the totality of the dataset from the ENLIGHTEN trials to evaluate next steps for pursuing an indication in non-polyp patients, as well as to continue development of LYR-210 in patients with nasal polyps Conference call to discuss trial results today at 8:30 a.m. ET WATERTOWN, Mass., June 02, 2025 (GLOBE NEWSWIRE) -- Lyra Therapeutics, Inc. (Nasdaq: LYRA) (“Lyra” or the “Company”), a clinical-stage biotechnology company developing long-acting, anti-inflammatory sinonasal implants for the treatment of chronic rhinosinusitis (CRS), today announced positive results from the ENLIGHTEN 2 Phase 3 clinical trial of LYR-210 in adult patients with CRS. The ENLIGHTEN 2 trial met its primary endpoint, with LYR-210 demonstrating statistically significant improvement compared to sham control in a composite of the three cardinal symptoms (3CS) of CRS (nasal obstruction, nasal discharge, facial pain/pressure) at week 24 (-1.13; p=0.0078) in patients without nasal polyps. The ENLIGHTEN 2 trial also met the key secondary endpoints of 3CS at 24 weeks in the full population (i.e., patients with and without nasal polyps) (-0.90; p=0.0209) and in the clinically-validated SNOT-22 score at 24 weeks (-8.7; p=0.0101), with symptom improvement observed as early as week 4. Consistent with previous studies, LYR-210 was well-tolerated, with a safety profile similar to sham control. The ENLIGHTEN program consists of two Phase 3 clinical trials, ENLIGHTEN 1 and ENLIGHTEN 2, to evaluate the efficacy and safety of LYR-210 for the treatment of CRS. While the ENLIGHTEN 2 trial met its primary endpoint and key secondary endpoints, the ENLIGHTEN 1 trial did not meet the primary endpoint or secondary endpoints, as previously reported in May 2024. Each ENLIGHTEN trial has enrolled approximately 180 CRS patients who have failed medical management and have not had prior ethmoid sinus surgery, randomized 2:1 to either LYR-210 (7500µg mometasone furoate) or sham control. The 24-week endpoints in the ENLIGHTEN trials assess LYR-210’s long-acting therapeutic effect as a bioresorbable nasal implant designed to deliver six months of continuous anti-inflammatory medication to the sinonasal passages. Results for Primary and Key Secondary Endpoints from ENLIGHTEN 2 Phase 3 Trial Patients reported LYR-210 significantly improved important outcome measures on primary and key secondary endpoints: Statistically significant improvement compared to sham control in a composite of the 3CS of CRS at week 24 (-1.13; p=0.0078) in patients without nasal polyps. Statistically significant improvement in 3CS with LYR-210 compared to sham control at week 24 (-0.90; p=0.0209) in the full population (i.e., patients with and without nasal polyps) Statistically significant improvements in Sino-Nasal Outcome Test (SNOT-22) score with LYR-210 compared to sham control at week 24 (-8.7; p=0.0101) Improvements in SNOT-22 were observed as early as week 4 with LYR-210 compared to sham control (-6.4; p=0.0456) Improvements in SNOT-22 were sustained throughout the trial and were clinically meaningful, with more than twice the minimal clinically important difference observed at week 24 compared to baseline in the LYR-210 group (-22.4 points) Data evaluating computed tomography (CT) scans demonstrated numerical improvement in ethmoid sinus opacification in patients who received LYR-210, compared to sham control at week 20 (-2.15; p=0.1809). These data provide objective radiological evidence of improvement with LYR-210 treatment. LYR-210 patients showed no difference from sham patients in use of corticosteroid rescue medication; however, the LYR-210 patients had fewer endoscopic sinus surgeries compared to sham control. Improvements in SNOT-22 were observed as early as week 4 with LYR-210 compared to sham control (-6.4; p=0.0456) Improvements in SNOT-22 were sustained throughout the trial and were clinically meaningful, with more than twice the minimal clinically important difference observed at week 24 compared to baseline in the LYR-210 group (-22.4 points) LYR-210 was well tolerated, with no product-related serious adverse events in the ENLIGHTEN 2 trial. The most commonly reported adverse events included epistaxis, upper respiratory tract infection, chronic sinusitis, acute sinusitis, nasopharyngitis, COVID-19, and headache. Results for CRS Patents with Nasal Polyps in Pooled Analysis from ENLIGHTEN 1 and ENLIGHTEN 2 Additionally, Lyra conducted a pooled data analysis of a total of 64 CRS patients with small nasal polyps (grade 1) from the ENLIGHTEN 1 and ENLIGHTEN 2 trials. The data demonstrated a consistent positive trend compared to sham control over 24 weeks in multiple endpoints: Improvement in 3CS with LYR-210 compared to sham control at week 24 (-1.13; p=0.0837), starting as early as week 4. Improvement in SNOT-22 score with LYR-210 compared to sham control at week 24 (-8.7; p=0.1331), starting as early as week 4. Improvements in percent ethmoid opacification with LYR-210 compared to sham control at week 20 (-6.07; p=0.1127). Improvements in nasal congestion score (NCS) with LYR-210 compared to sham control at week 24 for patients with moderate to severe NCS at baseline (-0.33; p=0.2159), starting as early as week 4. Improvements in nasal polyp score with LYR-210 compared to sham control at week 24 (-0.16; p=0.3494). "We are thrilled to announce these positive results from our ENLIGHTEN 2 trial. We believe this has the potential to provide a path to advance LYR-210 to treat CRS, offering six months of therapy in a single administration for millions of patients who do not respond to standard CRS medical management. We will continue to review the totality of the dataset from the ENLIGHTEN trials to optimize our regulatory strategy,” said Maria Palasis, Ph.D., President and CEO, Lyra Therapeutics. “Given these data we reported today, we plan to align with the FDA on a path forward for an NDA submission in patients without nasal polyps. As planned, we also analyzed the pooled data from ENLIGHTEN 2 and ENLIGHTEN 1 trials to treat CRS patients with nasal polyps, and we believe this positive data positions us to proceed with a development plan in patients with nasal polyps, based on our alignment in December 2024 with FDA on endpoints, inclusion criteria, patient population, background therapy, and assessments. Looking further ahead, we envision LYR-210 achieving its potential to benefit both non-polyp and polyp patients, positioning us to become a leader in CRS and validating our platform for future ENT indications.” “The positive results seen in the ENLIGHTEN 2 study are impressive and represent what could be a promising new treatment approach for the many CRS patients that I see every day in my practice who are underserved by limited therapies,” said Zachary Soler, M.D., MSc, Professor in the Department of Otolaryngology-Head and Neck Surgery at the Medical University of South Carolina and coordinating Lead Investigator for the ENLIGHTEN 2 trial. “The more than 20-point improvement from baseline in SNOT-22 score after LYR-210 treatment represents a clinically meaningful improvement in patient symptoms.” “These positive results represent a significant milestone in advancing an innovative treatment to CRS patients who suffer from this chronic condition. It's a proud moment for us and a testament to the dedication of this team and our investigators in the development of this novel therapy,” said Harlan Waksal, M.D., Executive Chairman, Lyra Therapeutics. Results from the ENLIGHTEN 2 trial of LYR-210 are planned to be presented at the 71st Annual Meeting of the American Rhinologic Society, October 2025. Conference Call and Webcast Lyra Therapeutics will host a conference call and webcast to discuss results from the ENLIGHTEN 2 trial today, June 2, 2025, beginning at 8:30 a.m. ET. To join the audio call please register via this audio link, or to view the livestreamed webcast visit this webcast link. A replay of the webcast and presentation will be available following the conference call in “Events and Presentations” in the Investors section of Lyra’s website for a limited time. About LYR-210 LYR-210 is an investigational product candidate for the treatment of chronic rhinosinusitis (CRS) in patients who have failed current therapies and require further intervention. LYR-210 is a bioabsorbable nasal implant designed to be inserted in a simple, in-office procedure. LYR-210 is intended to deliver six months of continuous anti-inflammatory therapy, mometasone furoate, to the sinonasal passages to treat CRS. About Lyra Therapeutics Lyra Therapeutics, Inc. is a clinical-stage biotechnology company developing long-acting, anti-inflammatory sinonasal implants for the treatment of chronic rhinosinusitis (CRS). Lyra Therapeutics is developing therapies for CRS, a highly prevalent inflammatory disease of the paranasal sinuses which leads to debilitating symptoms and significant morbidities. LYR-210, the company’s lead product, is a bioabsorbable nasal implant designed to be administered in a simple, in-office procedure and is intended to deliver six months of continuous anti-inflammatory drug therapy (7500µg mometasone furoate) to the sinonasal passages for the treatment of CRS with a single administration. LYR-210, which was evaluated in the ENLIGHTEN Phase 3 clinical program, is intended for patients with and without nasal polyps. The company’s therapies are intended to treat the estimated four million CRS patients in the United States who fail medical management each year. For more information, please visit www.lyratx.com and follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The words “believe,” “may,” “will,” “estimate,” “envision,” “continue,” “anticipate,” “intend,” “expect,” and similar expressions are intended to identify forward-looking statements. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements regarding our evaluation and investigation of the ENLIGHTEN 2 results and how they inform our path forward, our planned regulatory interaction and path for LYR-210, including alignment with the FDA and any planned regulatory submissions, our ability to design, implement and complete a new Phase 3 trial, the expected label for LYR-210, whether the pooled results from ENLIGHTEN 1 and 2 would support a path forward to a pivotal study in CRSwNP, our ability to correctly interpret FDA guidance received in December 2024 including on endpoints, inclusion criteria, patient population, background therapy, and assessments, whether LYR-210, if advanced, would be positioned to align with current ENT practices, and statements regarding the potential market opportunity for LYR-210, our participation in future events and presentations, and the timing of any of the foregoing. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause the Company's actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the Company’s failure to meet its primary endpoint in its ENLIGHTEN 1 Phase 3 clinical trial; the fact the Company terminated the employment of approximately 87 employees following the announcement that it failed to attain the primary endpoint of its ENLIGHTEN 1 Phase 3 clinical trial; the fact that the Company has incurred significant losses since inception and expects to incur additional losses for the foreseeable future; the Company's need for additional funding, which may not be available; the fact that the Company needs to conduct at least one additional phase 3 clinical trial; the Company’s ability to continue as a going concern; the Company’s limited operating history; the fact that the Company has no approved products; the fact that clinical trial data is subject to change until the completion of the applicable clinical study report; the fact that clinical trials required for the Company’s product candidates are expensive and time-consuming, and their outcome is uncertain; effects of recently enacted and future legislation; the possibility of system failures or security breaches; effects of significant competition; the Company's reliance on third parties to conduct its preclinical studies and clinical trials; failure to obtain and maintain or adequately protect the Company's intellectual property rights; failure to retain key personnel; the fact that the price of the Company's common stock may be volatile and fluctuate substantially; significant costs and required management time as a result of operating as a public company and any securities class action litigation. These and other important factors discussed under the caption "Risk Factors" in the Company's Quarterly Report on Form 10-Q filed with the SEC on May 6, 2025 and its other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While the Company may elect to update such forward-looking statements at some point in the future, it disclaims any obligation to do so, even if subsequent events cause its views to change. Contact Information: Jason Cavalier Chief Financial Officer 917.584.7668 jcavalier@lyratx.com Media Contact: Kathryn Morris The Yates Network LLC 914.204.6412 kathryn@theyatesnetwork.com

同写意年度巨献！！T20+大会特设“细胞药物创新前沿”分会，目前已确认体内CAR-T方向报告：A novel lentiviral based platform for in vivo CAR-T generatio孙敏敏：易慕峰医药创始人、董事长兼CEOIn vivo CAR-T therapy powered by novel CLAMP technology for T cell-Targeted mRNA delivery刘雅容：沙砾生物创始人/CEO阿斯利康在体内CAR-T领域发力了。5月20日，这家全球制药巨头宣布完成对EsoBiotec的收购，交易总价值高达10亿美元（包括4.25亿美元前期付款和5.75亿美元里程碑付款）。EsoBiotec作为体内细胞疗法的先驱，其核心技术有望彻底改变CAR-T疗法的开发模式，使其从复杂的体外制造转向更高效、更经济的体内递送。这一收购不仅标志着阿斯利康在肿瘤免疫治疗领域的进一步布局，更预示着体内CAR-T疗法即将迎来爆发式发展。本质上是赌注“细胞疗法的小型化与即时化”将成为未来标准。站在浪潮之巅的EsoBiotec，或许正是打开未来之门的钥匙之一。TONACEA01为何是EsoBiotec？2017年，全球首款CAR-T细胞疗法Kymriah获批，标志着肿瘤治疗进入“活体药物”时代。这种通过基因改造患者自身T细胞来精准杀伤癌细胞的技术，在血液肿瘤中展现出前所未有的疗效——某些难治性白血病的完全缓解率超过80%。然而，8年过去，CAR-T疗法仍面临生产成本高、制造周期长、针对实体瘤疗效有限三大瓶颈。为突破限制，产业界聚焦三种创新路径。通用型CAR-T（UCAR-T）：利用健康供体细胞，降低生产成本（如Allogene Therapeutics）；双靶点/逻辑门CAR-T：提升实体瘤识别能力（如临床阶段的CD19/CD22双靶点疗法）；体内CAR-T：跳过体外制造环节，直接体内改造T细胞——这正是EsoBiotec的核心战场。体内CAR-T通过静脉注射基因递送系统，直接在患者体内完成T细胞重编程，这种模式可缩短治疗周期至72小时内，成本有望降至10万美元以下。除了上述底层逻辑外，阿斯利康愿意支付10亿美元溢价，源于EsoBiotec的技术突破。EsoBiotec的工程纳米抗体慢病毒（ENaBL）平台，借助高度靶向的慢病毒作为载体，这类具备免疫屏蔽特性的慢病毒载体，能有效抵御免疫系统攻击，确保将遗传指令精准无误地传递至T细胞，从而在体内高效地将T淋巴细胞重编程为特定功能细胞。以针对多发性骨髓瘤的ESO-T01疗法为例，平台可将T细胞编程为 BCMA CAR-T细胞，使其精准识别并紧密结合表达BCMA的肿瘤细胞，激活免疫反应以杀伤肿瘤，展现出极高的精度与效力 。ENaBL平台采用模块化技术，具有卓越的兼容性，可适配多种细胞类型，广泛应用于不同的治疗领域。这一特性为开发多样化的细胞疗法奠定了坚实基础。基于此平台开发的疗法，极大地革新了传统治疗模式。它属于“现成”单剂量方案，患者无需进行淋巴细胞清除，仅需一次静脉注射，10分钟内即可完成给药，显著简化了治疗流程，减轻了患者身体负担，降低了时间成本。同时，得益于可扩展的生产工艺，能为全球供应提供可靠且经济高效的处理方法，相较于传统体外CAR-T疗法，成本有望降低一个数量级，大幅提升了癌症治疗的可及性 。目前，依托ENaBL平台，EsoBiotec已布局四条临床候选管线，其中针对多发性骨髓瘤的候选管线ESO-T01（BCMA CAR-T）已进入临床研究阶段。对于此番并购，阿斯利康肿瘤研发执行副总裁Susan Galbraith也颇为期待，表示EsoBiotec的技术“有可能改变细胞疗法”，“以便全球更多患者能够获得这些疗法”。TONACEA02阿斯利康的“如意算盘”2014年，当肿瘤免疫治疗初现曙光时，阿斯利康在肿瘤领域的管线显得黯淡无光。十年后的今天，它构建起一个肿瘤免疫帝国，其产品组合覆盖PD-L1抑制剂、ADC药物、细胞疗法等前沿领。这些交易构成阿斯利康肿瘤免疫版图的骨架，每笔都精准填补技术空白。拿下EsoBiotec公司，透露出阿斯利康对于CAR-T风口的渴望。自2012年基因泰克前CEO帕斯卡尔·索里奥特加盟以来，阿斯利康就将肿瘤设定为未来的战略重心。奥希替尼、阿卡替尼、度伐利尤单抗、德曲妥珠单抗等爆款频出，涵盖了三代EGFR抑制剂、BTK抑制剂、PD-1单抗、ADC药物等热门赛道，但唯独CAR-T赛道并没有看到阿斯利康的身影。纵观全球CAR-T竞争格局，吉利德、诺华、BMS为传统豪强，强生通过引进传奇生物的Carvykti，也割据了属于自己的市场。由于传统CAR-T药物靶点同质化较高，再加上高企的生产成本，这使得后来者很难再跻身进入这个赛道，这或许就是阿斯利康一直以来的遗憾。2023年，阿斯利康收购亘喜生物，获得FasTCAR平台，将CAR-T生产周期从2-6周缩短至24小时，显著提升血液肿瘤治疗效率。2024年对EsoBiotec的10亿美元收购，标志着阿斯利康完成了从"跟随者"到"规则制定者"的华丽转身。其布局始终紧扣"技术突破"与"临床可及性"两大核心。一方面，阿斯利康现有管线强于ADC和PD-1抑制剂（如Imfinzi），但缺乏细胞治疗抓手。EsoBiotec的ESO-101可与Imfinzi联用，构建“CAR-T+免疫检查点”组合拳。阿斯利康的布局揭示了一个深层逻辑：未来的癌症治疗不再是单一药物的竞争，而是技术生态系统的对抗。当PD-1抑制剂、ADC药物和细胞疗法在一个患者的治疗路径中无缝衔接时，真正的突破才会到来。确定的是，在肿瘤免疫时代，胜利属于那些能够整合多元技术、构建完整生态的企业。从Imfinzi到Enhertu再到EsoBiotec，每笔交易都不仅是产品的补充，更是技术能力的跃迁。随着肿瘤治疗从"粗放型"向"精准型"转变，这个价值240亿美元的肿瘤免疫帝国，正在书写癌症治疗的新范式——在这里，治愈癌症不再是遥不可及的梦想，而是可预期的医疗现实。