Pirfenidone

On track to complete enrollment of MIST Phase 2b trial of AP01 in progressive pulmonary fibrosis (PPF) in mid-2026, with newly presented long term open-label extension clinical data that support favorable tolerability profile Enrollment underway in AURA Phase 2 trial of AP02 in patients with idiopathic pulmonary fibrosis (IPF) with topline data anticipated by the end of 2027 Upsized initial public offering (IPO) gross proceeds of $345.0 million, together with approximately $123.1 million in cash, cash equivalents, and marketable securities as of March 31, 2026, projected to be sufficient to fund operations into 2029 BOSTON, June 03, 2026 (GLOBE NEWSWIRE) -- Avalyn Pharma Inc. (Nasdaq: AVLN), a clinical-stage biopharmaceutical company pioneering inhaled therapies to transform the treatment paradigm of serious, rare respiratory diseases, today announced financial results for the first quarter ended March 31, 2026 and recent business highlights. “Our recent IPO marks a transformative moment for Avalyn, providing the capital to advance three potentially paradigm-shifting programs in pulmonary fibrosis, a disease where current oral antifibrotics are limited by tolerability challenges that prevent many patients from receiving the full benefit of treatment," said Lyn Baranowski, CEO of Avalyn Pharma. "By delivering inhaled therapies directly to the lungs through nebulization, our programs are designed to address the urgent gap in treatments for these deadly diseases. The combination of anti-fibrotic activity seen in our clinical trials to date, together with the open-label extension data to be presented at EULAR in patients with PPF, reinforce our conviction that improved tolerability can unlock the potential for extended duration of treatment and clinical benefit. With clinical readouts across each of our three programs expected in 2027, we are executing with focus and discipline as we work to redefine the standard of care for patients living with this devastating disease." Recent Pipeline Progress AP01 (inhaled pirfenidone) MIST Phase 2b Trial On-Track to Complete Enrollment Mid-2026, with Multiple Recent Presentations Supporting its Clinical Profile. MIST is an ongoing Phase 2b randomized, double blind, placebo-controlled trial evaluating two doses of AP01 in patients with PPF. This 375-patient, 52-week trial is designed to assess safety and efficacy of AP01 with a primary endpoint of change in lung function measured by FVC. Enrollment is on-track to be completed mid-2026 with topline data anticipated in the second half of 2027. On June 6, 2026, the Company will present data from the PPF compassionate use cohort of its ATLAS open-label extension study at the European Alliance for Associations for Rheumatology (EULAR) Conference. Patients in this compassionate use cohort had late stage disease with no other treatment options. Study results indicate that after four years, AP01 remains generally well tolerated in these patients with PPF, with an adverse event pro with that observed in the ATLAS Phase 1b trial. Though this study was not designed for efficacy, a favorable trend in lung function trajectory as measured by FVC was seen out to 48 months compared with published data. These AP01 data, combined with previously reported long-term extension data in patients with IPF, suggest the potential for AP01 to impact disease progression and survival in patients with pulmonary fibrosis. In May 2026, Avalyn presented two posters at the American Thoracic Society (ATS) Annual Meeting in Orlando, FL, demonstrating its commitment to patients, and both hearing and addressing their concerns. Posters summarized how patient, care partner, and physician input informed improvements in instruction materials for the eFlow ® Nebulizer System for AP01, and described the importance of healthcare communication from the patient perspective. AP02 (inhaled nintedanib) Enrollment Underway in AURA Phase 2 Trial. In March 2026, Avalyn announced first patient dosing in its AURA trial of AP02 . AURA is a Phase 2 randomized, double-blind trial evaluating two doses of AP02 administered twice daily in patients with IPF. The 12-week study is designed to enroll 160 patients to assess safety and efficacy, as measured by FVC, with topline data anticipated in late 2027. AP03 (inhaled combination of nintedanib and pirfenidone) Development Underway as Next-Generation Fixed-Dose Combination Therapy: A Phase 1 trial of AP03, a therapeutic approach combining nebulized pirfenidone and nintedanib, is on track to initiate by the end of 2026. Recent Corporate Highlights In May 2026, the Company completed an upsized IPO, with the sale of 19,166,667 shares of its common stock, which included the full exercise by the underwriters of their option to purchase an additional 2,500,000 shares of common stock, at $18.00 per share. The Company raised gross proceeds of approximately $345.0 million, before deducting underwriting discounts and commissions and other offering expenses. Avalyn further strengthened its team to support the next phase of growth with the appointments of Adam Golden as General Counsel and Head of Business Development, and Frank Salisbury as Senior Vice President, Commercial. Upcoming Conference Jefferies Global Healthcare Conference, New York City. Management will present a company overview on Thursday, June 4, 2026, at 9:55-10:25 a.m. ET. Access to the webcast can be found here . Financial Results for First Quarter 2026 Cash Position: Cash, cash equivalents, and marketable securities were $123.1 million as of March 31, 2026. This amount excludes the net proceeds of approximately $316.1 million raised with the company’s IPO in May 2026. The company’s current cash, cash equivalents, and marketable securities, including the net proceeds from its IPO, are projected to be sufficient to fund its current operating plans into 2029. Research & Development (R&D) Expenses: R&D expenses were $22.9 million for the first quarter of 2026, as compared to $15.3 million for the first quarter of 2025. The increase in R&D expenses was primarily driven by the progression of the AP01 Phase 2b trial and on-going open label extension study, as well the AP02 Phase 2 trial. General & Administrative (G&A) Expenses: G&A expenses were $5.0 million for the first quarter of 2026, as compared to $3.4 million for the first quarter of 2025. The increase in G&A expenses was primarily driven by personnel-related expenses, including stock-based compensation. Net loss: Net loss was $26.9 million for the first quarter of 2026, as compared to $17.5 million for the first quarter of 2025. About Avalyn Pharma Avalyn aims to transform the treatment paradigm for pulmonary fibrosis and other serious, rare respiratory diseases. The company is advancing optimized inhaled formulations of established antifibrotic medicines designed to deliver drug directly to the lungs, enhance local efficacy, and reduce systemic side effects. Avalyn’s AP01 program is an optimized inhaled formulation of pirfenidone currently being evaluated in MIST, a global Phase 2b clinical trial in patients with progressive pulmonary fibrosis (PPF). AP01 has indicated encouraging safety and clinical activity across Phase 1b and multi-year open-label extension trials, with long-term data supporting the potential to preserve lung function while improving tolerability relative to historical oral pirfenidone. Avalyn’s AP02 program is an optimized inhaled formulation of nintedanib currently being evaluated in AURA, a global Phase 2 clinical trial in patients with idiopathic pulmonary fibrosis (IPF). Avalyn is also advancing AP03, an inhaled fixed-dose combination of pirfenidone and nintedanib, designed to deliver multiple antifibrotic mechanisms through a single lung-targeted platform. By leveraging its proprietary drug-device approach and deep expertise in rare respiratory disease development, Avalyn aims to establish a new standard of care in pulmonary fibrosis through inhaled, lung-targeted therapies. For more information, please visit avalynpharma.com and follow the company on LinkedIn . Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, without limitation, implied and express statements about Avalyn’s beliefs and expectations regarding: the anticipated enrollment of the MIST Phase 2b trial of AP01 in PPF in mid-2026 and the interpretation and potential implications of clinical data; the ongoing enrollment in the AURA Phase 2 trial of AP02 in patients with IPF and the expected timing of results by the end of 2027; the potential of its product candidates to address significant unmet needs in the treatment of pulmonary fibrosis and related diseases; the possibility that improved tolerability may translate into clinically meaningful benefit; the advancement of its pulmonary fibrosis programs; the planned initiation of a Phase 1 trial of AP03 by the end of 2026; and the potential for any of the Company’s product candidates to establish or contribute to a new standard of care; and Avalyn’s expectations regarding the anticipated timeline of its cash runway and future financial performance. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the risk that earlier results may not be indicative of future results, risks related to clinical trial site activation, delays in enrollment generally or enrollment rates that are lower than expected; delays related to assessment of clinical trial results; risks related to unexpected safety or efficacy data observed during clinical studies; risks related to volatile market and economic conditions, risks related to our ability to protect and maintain our intellectual property position or relationships with third-parties, the initiation, timing, progress and results of our current and future research and development programs, preclinical studies and clinical trials; our ability to successfully complete our clinical trials; our ability to advance any product candidates that we may identify and successfully complete any clinical studies, including the manufacture of any such product candidates; the likelihood of our clinical trials demonstrating safety and efficacy of our product candidates; and risks related to needs for additional financing. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Avalyn’s current and future filings with the Securities and Exchange Commission, including those described from time to time under the caption “Risk Factors.” In addition, any forward-looking statements represent Avalyn’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Avalyn explicitly disclaims any obligation to update any forward-looking statements subject to any obligations under applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Investor Contact: Cassie Saitow, Avalyn Pharma Inc. Sr. Director, IR and Corporate Communications ir@avalynpharma.com Media Contact: Kat Lippincott, Deerfield Group kat.lippincott@deerfieldgroup.com media@avalynpharma.com Financial Tables AVALYN PHARMA INC. CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS (In thousands, except share and per share amounts) (Unaudited) Three Months Ended March 31, 2026 2025 OPERATING EXPENSES: Research and development $ 22,889 $ 15319 General and administrative 5,020 3397 Total operating expenses 27,909 18716 LOSS FROM OPERATIONS (27,909 ) (18,716 ) OTHER INCOME (EXPENSE): Interest income 1,125 1248 Interest expense (98 ) — Other expense 13 (35 ) Total other income 1,040 1213 NET LOSS $ (26,869 ) $ (17503 ) AVALYN PHARMA INC. CONSOLIDATED BALANCE SHEET DATA (In thousands) (Unaudited) March 31, December 31, 2026 2025 Cash, cash equivalents, and marketable securities $ 123,127 $ 138359 Total assets 135,663 148881 Total liabilities 27,687 15316 Total stockholders’ deficit and redeemable convertible preferred stock $ 107,976 $ 133565

*仅供医学专业人士阅读参考病理分型细化、免疫巩固前移、双抗联合崛起、后线靶向破局。整理 | 易艾蓝在刚刚落幕的2026年中国临床肿瘤学会（CSCO）指南发布会上，复旦大学附属中山医院胡洁教授、解放军总医院汪进良教授、中国医学科学院肿瘤医院毕楠教授对SCLC的病理诊断、内科治疗及放射治疗策略修订进行了解读。此次更新不仅纳入了多项中国学者的原创性研究，更标志着SCLC诊疗正式迈入“精准分型+全程管理”的2.0时代。本文将为您深度解读此次指南更新的四大核心维度。病理诊断升级：从“形态学”迈向“分子分型”SCLC的病理诊断正从单纯的形态学向“分子分型”迈进。胡洁教授指出，新增的神经内分泌标记物INSM1凭借其细胞核定位优势，能更精准地辅助诊断；而P53/RB1的双重异常模式则是确诊SCLC的分子金标准。更重要的是，指南强调了病理报告中需明确是否存在混合性非小细胞癌成分，这不仅解决了诊断难题，更为后续的精准治疗提供了决定性依据。1病理学诊断 注释：神经内分泌肿瘤标志物包括CDS6、Sm.GoA，在具有神经内分泌肿瘤形态学特征的基础上至少有一种神经内分泌免疫组化标志物明确阳性，且神经内分泌标记阳性的细胞数应大于10%肿瘤细胞数才可诊断神经内分泌肿瘤。明确的鳞状细胞癌或腺癌伴神经内分泌分化并不影响治疗决策或预后TTF-1在85%~90%的小细胞肺癌中呈阳性表达(但此时TTF-1阳性表达不能区分肺小细胞癌或肺外小细胞癌，因为20%~80%肺外部位，如胃肠道、膀胱、子宫颈、前列腺等处发生的小细胞癌亦可表达TTF-1)当少数小细胞肺癌病例中不表达神经内分泌标志物时，结合形态、TTF-1弥漫阳性、CX核旁点状阳性颗粒特点及高K-67指数(一般为50%~100%)也有助于小细胞癌的诊断2小细胞肺癌病理诊断报告原则新增：SCLC 病理诊断报告原则中需关注是否存在其他非小细胞癌组织学类型成分（必备信息），具有非典型形态时加备注（可选信息）。 3分子标志物新增：分子标志物检测中SCLC的二线治疗（6个月以上复发）新增肿瘤标志物DLL3（III级推荐，2B类） 注释：新增DLL3靶点新增SEZ6靶点新增B7H3靶点新增MHC-I相关特征与免疫治疗新增外周血蛋白组学新证据新增多组学联合分析新证据内科治疗：全程管理的重塑SCLC的内科治疗已突破“化疗耐药后无药可用”的瓶颈，进入了“双抗+双靶”的全程管理新时代。汪进良教授强调，一线治疗中索卡佐利单抗等双抗药物的引入，以及后线治疗中全球首个靶向DLL3的T细胞衔接器塔拉妥单抗的获批，标志着SCLC正式迈入靶向治疗元年。这些突破性药物不仅显著延长了患者的生存期，更将治疗选择从“无药可医”转变为“有药可用”。1局限性SCLC的初始治疗更新要点：T1-2，N0无更新超过T1-2，N0：上调“同步放化疗后无进展患者，度伐利尤单抗巩固治疗2年”作为Ⅰ类推荐 2广泛期SCLC初治及一线维持治疗更新要点：无局部症状且无脑转移患者一线及维持治疗 I 级推荐中，调整化疗 + 免疫治疗（I 级推荐）作为“优选”推荐；无局部症状且无脑转移患者一线及维持治疗I 级推荐中，新增“索卡佐利单抗 + 依托泊苷 + 卡铂 4 周期后索卡佐利单抗维持治疗”为“I 级推荐”方案；无局部症状且无脑转移患者一线及维持治疗II 级推荐中，新增“阿替利珠单抗 + 依托泊苷 + 卡铂 4 周期后芦比替定联合阿替利珠单抗维持治疗”为“II 级推荐”方案；新增“伴骨转移”分层，补充了骨保护药物的临床建议。 3广泛期SCLC后线治疗更新要点：删除小细胞肺癌二线治疗Ⅲ级推荐“苯达莫司汀”新增“塔拉妥单抗”作为小细胞肺癌二线治疗Ⅱ级推荐(1A类)新增“塔拉妥单抗”作为小细胞肺癌三线及以上治疗Ⅱ级推荐(1A类) 放射治疗：免疫时代的协同与挑战随着免疫巩固治疗成为标准，放疗的角色也在发生深刻变化。毕楠教授指出，ADRIATIC研究证实，无论采用何种放疗模式（常规或大分割），后续衔接度伐利尤单抗均能带来生存获益，这为临床灵活制定放疗方案提供了底气。然而，放疗与免疫的联合也带来了新的挑战——“放射-免疫复合伤”。指南特别细化了放射性肺损伤与免疫相关肺炎的鉴别标准，旨在平衡疗效与安全性。1局限期 SCLC 初始治疗局限期 SCLC 胸部放疗注释（4）新增了证据（新增加粗部分）：放疗总剂量和分割方案：目前尚未确定最佳的放疗剂量和分割方案。根据 INT0096 研究，45 Gy/1.5 Gy，每天 2 次 /3 周方案优于 45 Gy/1.8 Gy，每天 1 次 /5 周方案。而两项 III 期研究 CONVERT 研究和 RTOG0538 研究均未能证明 66 Gy 或 70 Gy（每天 1 次）方案优于 45 Gy（每天 2 次）方案，但前者的总生存率和毒性均与后者相似 [13, 30]，因此推荐局限期 SCLC 患者胸部放疗总剂量为 45 Gy/1.5 Gy，每天 2 次 /3 周或总剂量为 60～70 Gy，1.8～2.0 Gy，每天 1 次 /（6～8 周）。回顾性和随机 II 期研究表明，加速大分割方案总剂量为 40～42 Gy（每天 1 次，3 周完成）可产生与 45 Gy/1.5 Gy，每天 2 次相似的结果。一项中国 III 期研究显示 45 Gy/3 Gy/15 次的大分割放疗方案与高剂量常规分割放疗相比（60 Gy/2 Gy/30 次）生存相似；但大分割放疗组显示出更高的安全性，≥3 级急性治疗相关不良事件的发生率显著较低（48.7% vs. 67.7%，P近期随机对照 II 期研究和回顾性研究显示，如果可以安全地给予更高剂量（60 Gy/40 次，每天 2 次]；65 Gy/26 次，每天 1 次；或肿瘤同步加量至 54 Gy/30 次，每天 2 次），可能改善 OS 或 PFS。一项中国 III 期随机对照临床研究（NCT03214003）对比了高剂量 [计划靶区（planning target volume，PTV）给予 45 Gy/30 次，大体肿瘤靶区（gross tumor target volume, GTV）同步加量至 54 Gy/30 次，每天 2 次）] 和标准剂量（PTV 均一给量 45 Gy/30 次，每天两次）两种超分割方案，初步结果显示高剂量超分割方案可显著延长 OS 或 PFS。局限期 SCLC 内科治疗注释（5）新增了证据（新增加粗部分）：ADRIATIC 研究的成功也引发了关于 LS-SCLC 研究中免疫治疗介入时机、与免疫治疗联合的最佳胸部放疗分割方式，免疫治疗的不同药物和免疫治疗的时长，PCI 在 LS-SCLC 免疫治疗中的疗效和安全性，选择卡铂还是顺铂能够与 LS-SCLC 免疫治疗发挥最大协同作用等问题的深入思考。在免疫巩固治疗方面：ASTRUM-LC01 II 期研究（斯鲁利单抗巩固治疗 1 年）和 GASTO-1052 II 期研究（特瑞普利单抗巩固治疗 6 个月）均证实在 LS-SCLC 同步放化疗后使用免疫巩固治疗显著提高疗效（前者 PFS 中位数为 27.5 个月，后者尚未达到）。而 ACHILES II 期研究在同步放化疗后使用阿替利珠单抗巩固治疗未观察到生存获益。正在进行的 DeLLphi-306、HLX10-020-SCLC302、MK 7339-013/KEYLYNK-013 等研究结果值得期待。NRG LU005 研究同步放化疗中联合阿替利珠单抗治疗与同步放化疗相比并没有看到生存获益。目前免疫治疗从诱导治疗开始就介入的研究 SHR-1316-III-302 研究、HLX10-020-SCLC302 仍然在探索中。一项 II 期研究显示，卡瑞利珠单抗联合化疗诱导后序贯 cCRT 及免疫巩固治疗，在客观缓解率、无进展生存和总生存方面均优于单纯 cCRT。2广泛期SCLC的初始治疗广泛期SCLC放疗治疗更新（新增加粗部分）：一项胸部低剂量放疗（low-dose radiotherapy，LDRT）15 Gy/5 次同步一线阿替利珠单抗 + 依托泊苷 / 顺铂或卡铂，并阿替利珠单抗维持治疗的 I 期试验（MATCH试验）显示出肿瘤免疫微环境的重塑，良好的安全性和可行性，以及近期和中期疗效（ORR 为 73.3%，PFS 中位数为 6.9 个月），OS 中位数为 16.9 个月。1、3 年 PFS 率分别为 27.3% 和 20.7%，1 年和 3 年 OS 率分别为 69.9% 和 35.1%。进一步，相似设计的 LDRT（15 Gy/5 次）同步一线联合化疗与免疫治疗的 2 项前瞻性多中心I期临床试验进一步报道结果，安全性和耐受性均良好，联合度伐利尤单抗的 PFS 中位数和 OS 分别为 8.3 个月和 23.6 月（LEAD 试验）；联合斯鲁利单抗的 PFS 中位数为 7.3 个月，OS 中位数尚不成熟（SPUR 试验）。3放疗并发症的处理放射性肺损伤注释部分修改完善注释（3）对症支持治疗更新（新增加粗部分）：止咳、化痰、平喘治疗。另外，可考虑辅助抗纤维化治疗及中医药治疗，保持充足能量供给并补充多种维生素。Ⅱ 期研究发现吡非尼酮联合标准疗法能够改善放射性肺损伤（radiation induced lung injury，RILI）患者的肺功能、轻到中度放射性肺纤维化，但目前尚无 Ⅲ 期随机对照试验证据支持常规应用，仅推荐在临床试验背景下使用。注释（4）放射性和免疫性肺损伤共存更新（新增加粗部分）：对于（序贯或同期）合并使用免疫检查点抑制剂的患者，特别是免疫相关细胞因子明显变化的患者，在诊断放射性肺损伤的情况下，需注意同时合并免疫相关肺损伤（check point inhibitor pneumonitis, CIP）的可能性。这种复合性肺损伤的个案或回顾性报道自 2018 年以来逐步增多，部分患者糖皮质激素减量时症状反复，可能需使用其他免疫抑制剂。鉴别放射 - 免疫相关性肺炎对于其治疗至关重要。（1）在发病时机上，RILI 多在放疗后 6 个月内出现，尤其在放疗后 1～3 个月内较为常见，而 CIP 可能在治疗后 2～24 个月内的任何时间发生。（2）影像学上，RL 通常局限于放射区域内，表现为渗出实变和纤维化；CIP 的影像学表现则更为多样，可分为 5 种类型：隐源性组织性肺炎、磨砂玻璃样结节的磨玻璃样混浊、小叶间隔增厚的间质性肺炎、小叶中心结节的超敏反应性肺炎，以及未明确定义的肺炎。临床上，RILI 和 CIP 的鉴别常依据病变位置，RLI 多见于照射的高剂量区域，与放疗剂量参数紧密相关，而 CIP 则多见于高剂量区域之外。（3）在临床实践中，除了明确放射-免疫相关性肺炎的性质，还需与其他可能引起相似症状的疾病进行鉴别诊断。RIL 和 CIP 均为无菌性炎症，与感染性疾病相比，通常不伴有发热和白细胞升高等典型感染症状。感染性肺炎的影像学表现早期为毛玻璃样阴影，细菌性肺炎多局限于肺叶或肺段，而病不良反应肺炎则表现为多发毛玻璃样阴影。（4）此外，还需注意与肿瘤进展的鉴别后者常表现为咳嗽、咯血、胸痛、体重减轻、呼吸困难，肿瘤标志物可能升高，影像学上可见肺癌原发灶增大及新的结节状影、片状影、毛玻璃影等。放射性皮肤损伤注释部分修改完善更新（新增加粗部分）：因此，在进行局部治疗的同时，应积极进行全身治疗。目前在国内外相关指南和共识中，关于生长因子类或生物制剂类药物在放射性皮肤损伤预防与治疗中的应用推荐意见尚不统一。国内的相关指南、共识中，对于 EGF、GM-CSF 在放射性皮肤损伤 / 放射性皮炎中的预防或治疗性应用予以弱推荐。责任编辑：Sheep