Veligrotug

WALTHAM, Mass.--(BUSINESS WIRE)--Viridian Therapeutics, Inc. (Nasdaq: VRDN), a biotechnology company focused on discovering, developing and commercializing potential best-in-class medicines for autoimmune and rare diseases, today announced the pricing of its upsized underwritten public offering of $225.0 million aggregate principal amount of its 1.75% convertible senior notes due 2032 (the “Convertible Notes” and such offering, the “Convertible Notes Offering”) and its upsized underwritten public offering of 7,352,942 shares of its common stock at a public offering price of $17.00 per share (such offering, the “Equity Offering”). Viridian estimates that the aggregate net proceeds from the Convertible Notes Offering and the Equity Offering will be approximately $334.7 million, after deducting underwriting discounts and commissions and Viridian’s estimated offering expenses. In addition, Viridian has granted the underwriters of the Convertible Notes Offering a 30-day option to purchase up to an additional $25.0 million aggregate principal amount of Convertible Notes offered in the Convertible Notes Offering, solely to cover over-allotments and on the same terms and conditions. Viridian also granted the underwriters of the Equity Offering a 30-day option to purchase up to an additional 1,102,941 shares of its common stock, on the same terms and conditions. The Convertible Notes Offering and the Equity Offering are expected to close on May 11, 2026, subject in each case to the satisfaction of customary closing conditions. Neither the closing of the Convertible Notes Offering nor the closing of the Equity Offering is contingent upon the closing of the other offering. The Convertible Notes will be general, unsecured, senior obligations of Viridian and interest will be payable semi-annually in arrears on May 15 and November 15 of each year, beginning on November 15, 2026, at a rate equal to 1.75% per year. The Convertible Notes will mature on May 15, 2032, unless earlier converted, redeemed or repurchased by Viridian. Before February 15, 2032, noteholders may convert their Convertible Notes at their option only in certain circumstances. From, and including, February 15, 2032 until the close of business on the scheduled trading day immediately before the maturity date, noteholders may convert their Convertible Notes at any time at their option. Viridian will settle conversions by paying or delivering, as applicable, cash, shares of its common stock or a combination of cash and shares of its common stock, at Viridian’s election. The initial conversion rate is 40.5680 shares of Viridian’s common stock per $1,000 principal amount of the Convertible Notes, which is equivalent to an initial conversion price of approximately $24.65 per share of its common stock and represents a conversion premium of approximately 45.0% above the public offering price per share of its common stock in the Equity Offering. If a “make-whole fundamental change” (as defined in the indenture that will govern the Convertible Notes) occurs, then Viridian will in certain circumstances increase the conversion rate for a specified period of time. The Convertible Notes will be redeemable, in whole or in part (subject to certain limitations), at Viridian’s option at any time, and from time to time, on a redemption date on or after May 20, 2030 and on or before the 26th scheduled trading day immediately before the maturity date, at a cash redemption price equal to the principal amount of the Convertible Notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding, the redemption date, but only if the last reported sale price per share of its common stock exceeds 130% of the conversion price for the Convertible Notes on (1) each of at least 20 trading days, whether or not consecutive, during the 30 consecutive trading days ending on, and including, the trading day immediately before the date Viridian sends the related redemption notice; and (2) the trading day immediately before the date Viridian sends such notice. If a “fundamental change” (as defined in the indenture that will govern the Convertible Notes) occurs, then, subject to a limited exception, noteholders may require Viridian to repurchase their Convertible Notes at a cash repurchase price equal to the principal amount of the Convertible Notes to be repurchased, plus accrued and unpaid interest, if any, to, but excluding, the fundamental change repurchase date. Viridian intends to use the net proceeds from the Convertible Notes Offering and the Equity Offering to repay all outstanding indebtedness under the Loan and Security Agreement with Hercules Capital, Inc., to fund market expansion studies for its thyroid eye disease (“TED”) franchise, and to advance the research and development of its earlier pipeline, as well as for working capital and other general corporate purposes. Jefferies, Leerink Partners, and Goldman Sachs & Co. LLC are acting as joint book-running managers and LifeSci Capital is acting as lead manager for the Convertible Notes Offering. Jefferies, Leerink Partners, and Goldman Sachs & Co. LLC are acting as joint book-running managers and LifeSci Capital and Wedbush PacGrow are acting as lead managers for the Equity Offering. A registration statement relating to these securities has been filed with the Securities and Exchange Commission (SEC) and became effective on September 5, 2025. A final prospectus supplement and accompanying base prospectus relating to and describing the terms of each of the Convertible Notes Offering and Equity Offering will be filed with the SEC. The securities described above have not been qualified under any state blue sky laws. This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. The offering will only be made by means of a prospectus, copies of which may be obtained at the SEC’s website at , or by request to Jefferies LLC (Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, New York 10022; telephone: 877-821-7388; email: Prospectus_Department@Jefferies.com ); Leerink Partners LLC, Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, or by telephone at (800) 808-7525 ext. 6105, or by email at syndicate@leerink.com ; or Goldman Sachs & Co. LLC, Attn: Prospectus Department, 200 West Street, New York, NY 10282 (Tel: 866-471-2526) or by e-mail at prospectus-ny@ny.email.gs.com . About Viridian Therapeutics, Inc. Viridian is a biotechnology company focused on discovering, developing, and commercializing potential best-in-class medicines for patients with autoimmune and rare diseases. Viridian’s expertise in antibody discovery and protein engineering enables the development of differentiated therapeutic candidates for validated drug targets and disease-driving mechanisms in autoimmune and rare diseases. Viridian is advancing multiple late-stage, anti-insulin-like growth factor-1 receptor (“IGF-1R”) candidates in the clinic for the treatment of patients with TED. The company conducted a pivotal program for veligrotug, including two global phase 3 clinical trials, THRIVE and THRIVE-2, to evaluate its efficacy and safety in patients with active and chronic TED. THRIVE and THRIVE-2 reported positive topline data, meeting their primary endpoints and all secondary endpoints. Viridian is also advancing elegrobart as the potential first subcutaneous autoinjector for the treatment of TED. Viridian is conducting an ongoing pivotal program for elegrobart, including two ongoing global phase 3 pivotal clinical trials, REVEAL-1 and REVEAL-2, to evaluate the efficacy and safety of elegrobart in patients with active and chronic TED. REVEAL-1 and REVEAL-2 reported positive topline data, meeting their primary endpoints and multiple secondary endpoints. In addition to its IGF-1R inhibitor portfolio, Viridian is developing an anti–thyroid-stimulating hormone receptor (“TSHR”) program designed as a potential therapy for TED and Graves’ disease. Viridian is also advancing a novel portfolio of neonatal Fc receptor (“FcRn”) inhibitors, including VRDN-006 and VRDN-008, which have the potential to be developed in multiple autoimmune diseases. Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of words such as, but not limited to, “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” or “would” or other similar terms or expressions that concern the company’s expectations, plans and intentions. Forward-looking statements include, without limitation, statements regarding the timing and completion of the offerings on the anticipated terms, or at all; statements regarding the expected net proceeds of the offerings and the anticipated use of proceeds from the offerings; the company’s plans regarding commercial launch activities related to veligrotug and elegrobart and research and development activities; the company’s belief that its product candidates may be best-in-class; and the potential for the company’s novel portfolio of FcRn inhibitors to be developed in multiple autoimmune diseases. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on the company’s current beliefs, expectations and assumptions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to: market conditions that may affect the timing, terms or conditions of the underwritten public offerings; the company’s successful completion of the underwritten public offerings; the satisfaction of customary closing conditions related to the underwritten public offerings; and other risks and uncertainties identified in the company’s filings with the SEC, including those risks set forth under the caption “Risk Factors” in the company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, filed with the SEC on May 5, 2026, and other subsequent disclosure documents filed with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither the company, nor its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing the company’s views as of any date subsequent to the date hereof. Contacts Investors Greg Rossino grossino@viridiantherapeutics.com Media Lisa Lopez llopez@viridiantherapeutics.com

医道社：传承和发展民间中医 来源：海外网站 作者：医道社整理  版权归原作者所有，如有违规、侵权请联系我们删除！ 👆关注不迷路，更多创新药前沿资讯 大家好，我是你们的创新药观察者老汤。作为一个专注生物制药领域的微信公众号博主，我每天泡在临床试验数据、公司财报和行业海报里，试图从海量信息中挖出那些真正能改变患者命运的“黑马”。今天，我想和大家聊聊甲状腺眼病（TED）这个“隐形杀手”战场。TED不是简单的眼疾，而是从眼球突出到生活崩盘的慢性折磨，全球患者超100万，但现有治疗渗透率不足10%。Amgen/Horizon的Tepezza（teprotumumab）曾是革命者，证明IGF-1R靶点能逆转症状，但它的静脉输液模式让许多慢性患者望而却步。Viridian Therapeutics呢？他们不是在做“另一个Tepezza”，而是用elegrobart（VRDN-003）这种皮下注射（SC）长半衰期抗IGF-1R抗体，试图把TED治疗从“医院输液中心”带回“患者家里”。基于2024年ENDO、Innovate TED、ATA海报，以及2026年REVEAL-2顶线结果，我觉得这可能是TED赛道自Tepezza获批以来，最值得临床医生和研发人员重视的一次产业跃迁。准备好被这些数据震撼了吗？我们一步步来拆解。第一，TED的“隐形杀手”本质：不止眼突，更是生活质量崩盘 TED是与Graves病高度相关的自身免疫性眼眶疾病，核心痛点包括眼球突出（proptosis）、复视（diplopia）、眼睑退缩、炎症、疼痛，甚至视功能受损。全球发病率约25/10万，80%患者伴Graves病。根据美国甲状腺协会（ATA）2024年报告，重症患者眼球突出3-5mm，看起来像“瞪眼怪”，复视发生率高达50%，导致开车、阅读、工作全线瘫痪；角膜暴露风险升至30%，甚至永久失明。更残酷的是心理冲击：一项《Frontiers in Endocrinology》（2023）meta分析显示，TED患者抑郁率是普通人的3倍，生活质量评分（GO-QOL）平均下降40%。 我采访过一位TED患者（基于Patient Advocacy论坛真实案例）：她诊断后眼球突出5mm，戴墨镜出门成常态，工作丢了，社交崩了，镜子成了敌人。“我宁愿死，也不愿这样活。”慢性TED（症状>15个月）患者占比70%，他们往往被忽略，因为“稳定了就不疼”。但稳定？不过是慢性折磨！过去治疗依赖糖皮质激素、眶放疗、手术或支持性措施，疗效有限（缓解20%-30%），复发率高企50%。直到Tepezza出现（2020年FDA批准），IGF-1R机制才把TED拉进“靶向逆转时代”。Tepezza的Phase 3 OPTIC试验显示，proptosis响应率74%，平均改善2.5mm，但它是IV给药，8次输液，每3周一次，总成本超20万美元（Amgen 2023财报）。2023年Tepezza全球销售额19亿美元，但患者依从性仅60%，因为“去医院太累”——时间成本高、占用输液中心资源、听力相关不良事件（AE）始终是痛点。 这就是Viridian的机会：TED市场从“有没有药”切换到“谁更方便、谁更早用、谁覆盖更多患者”的第二战场。真正限制渗透率的，从来不只是药效，而是给药方式。Tepezza验证了“药有效”，Viridian要证明“怎么让更多患者愿意用”。第二，Viridian的双管齐下布局：从IV到SC，重塑TED药物形态 Viridian在TED上押注两条核心管线，共享IGF-1R靶向逻辑（阻断眼眶细胞增生），但面向不同竞争维度： ·Veligrotug（VRDN-001）：IV抗IGF-1R抗体，证明疗效、输注时间、治疗体验能挑战Tepezza。Phase 3 THRIVE试验（ATA 2024海报#0583）显示，5次输液后proptosis改善2.5mm，响应率67%。BLA推进中，PDUFA目标日期2026年6月30日。适合医院主导、快速导入场景。 ·Elegrobart（VRDN-003）：SC长半衰期抗IGF-1R抗体，更激进——从“医院输液”变“低频居家注射”。半衰期40-50天（VRDN-001仅10-12天），生物利用度≥60%。它不是简单“SC版”，而是经过工程化改造，为Q4W或Q8W方案而生。未来可能用autoinjector自注，覆盖慢性TED和可及性差人群。 这种组合打法聪明：IV卡住医生信心，SC推市场扩张。Viridian的目标不是单点挑战，而是形成分层治疗矩阵——急性用IV，慢性用SC。第三，2024年海报的“序章”信号：PK桥接+安全可行，方向对了 2024年的ENDO、Innovate TED、ATA海报不是普通Phase 1数据，而是提前埋下三个结论：VRDN-003是专为低频SC设计的分子；开发围绕有效暴露桥接；目标直指Q4W/Q8W+双适应症（活动期+慢性期）。 1.半衰期拉长，奠定低频基础：VRDN-003 40-50天（4-5倍于VRDN-001的10-12天）。这不是装饰，而是商业化起点：减少频率、血药平稳、易居家化。Phase 1健康志愿者（24名，300-600mg单/双剂）显示，暴露平稳。 2.SC暴露模拟覆盖IV有效区间：用2室PK模型桥接VRDN-001 IV参考（基于临床/建模）： ·IV 20mg/kg：Cmin 105 μg/mL，AUC 23,000 μg·day/mL ·IV 10mg/kg：Cmin 52 μg/mL，AUC 11,300 ·IV 3mg/kg：Cmin 13 μg/mL，AUC 3,200 VRDN-003 SC（600mg负荷+300mg维持）： ·Q2W：Cmin 132 μg/mL，AUC 18,900（对标高暴露IV） ·Q4W：Cmin 53 μg/mL，AUC 10,200（对标中暴露） ·Q8W：Cmin 14 μg/mL，AUC 5,800（对标低暴露，但仍有效） 这组数据关键：不是空谈SC有效，而是用暴露桥接证明临床成功概率高。三档方案对应不同患者场景，便于分层。 3.生物利用度不差，吸收可靠：SC ≥60%（与VRDN-001相似）。大分子SC最怕吸收不足/波动，Viridian避开这坑，直接推进III期。 4.早期安全性无红旗：小样本健康志愿者，未见严重AE、3/4级AE、听力损害、停药。注射反应有但轻微，全恢复。虽不能替代患者长期数据，但对SC/autoinjector是绿灯。AE仅3例（头痛、注射反应），无血小板减少或肝酶升高（Tepezza常见）。 这些数据说明：Viridian从一开始就不是“试剂量”，而是完整产品定义。很多时候，行业变革从形态设计开始——Viridian在这里领先。第四，2026 REVEAL-2的震撼顶线：慢性TED中，SC低频疗效不打折 如果2024年是“理论走得通”，2026年5月5日REVEAL-2结果就是现实证明。这项多中心、随机、安慰剂对照Phase 3，纳入204名慢性TED患者（症状>15个月，CAS 0-7，proptosis≥3mm），1:1:1随机至elegrobart Q4W（n=70，6针）、Q8W（n=68，3针）或安慰剂（n=66）。慢性TED传统响应率<30%（《JAMA Ophthalmology》2024回顾），但elegrobart大获全胜。 核心疗效（Week 24）： 1.FDA主要终点：proptosis响应率（≥2mm改善）：Q4W 50%，Q8W 54%，安慰剂15%（p<0.0001）。平均变化：Q4W -1.9mm，Q8W -2.1mm，安慰剂 -0.5mm。每1mm改善都是患者镜中新生——社交、职业、自我认同重塑。 2.EMA主要终点：整体响应率（proptosis + CAS无恶化）：Q4W 47%，Q8W 54%，安慰剂15%（p<0.0001）。综合维度成立。 3.复视响应率：Q4W 61%（p=0.0118），Q8W 55%（p=0.0419），安慰剂38%。Q4W统计显著，Q8W名义优势（需完整数据确认多重校正）。elegrobart不只改善“看起来”，还控功能症状。 4.其他：完全缓解率 Q4W 44%，Q8W 36%，安慰剂25%。91%完成治疗。 为什么震撼？ Q8W不输Q4W（点估计更高），证明低频不打折。PK模型匹配：Q8W暴露对标IV低剂量，但临床上更亮眼。《The Lancet Endocrinology》（2025预印）meta显示，IV IGF-1R在慢性TED响应率平均42%，需8-10次给药；elegrobart只需3针，自注在家！ 安全性：无治疗相关SAE。AE轻度：注射反应1%，听力损害安慰剂调整后Q4W 4.1%、Q8W 8.8%（低发，未见严重）。对比Tepezza Phase 4（NCT04583735，2025数据）：响应率62%，但听力15%、肌肉痉挛20%、IV感染5%。elegrobart“类Tepezza但更优”，如CEO Steve Mahoney所说：“吸引慢性患者主动求医。” REVEAL-1（活跃TED）已启动，预计2027双适应症。Innovate TED 2024（#P-11）强调，SC可提升依从性50%，减资源浪费。第五，为什么Viridian敢推Q4W和Q8W？商业哲学的分层布局 Q4W和Q8W不是“多试一组”，而是市场哲学： ·Q4W：稳健型，匹配医生随访，便于重症积极控制。 ·Q8W：便利最大化，强化家庭依从，适合慢性TED。24周仅3针，无需频繁医院，吸纳原本不治患者。 REVEAL-2中Q8W亮眼，证明PK设计落地。TD Cowen 2026报告预测，这将推慢性TED渗透率从10%到40%，额外50亿美元机会。SC生产成本低30%（BioPharm International 2025），定价或降20%，提升公平性。第六，这对Tepezza意味着什么？Viridian的突围点与风险 Tepezza护城河强：先发、认知、支付体系、真实世界经验。但Viridian有机会在体验、可及性上重定义： 1.给药代差：Tepezza 8次IV（每针1-2h，缺席30%，Health Economics Review 2024）；elegrobart Q8W 3针<10min，自注。 2.广覆盖：填慢性空白，远程/轻中度患者易入。 3.组合：IV+SC矩阵，比单品硬刚危险。Amgen SC Tepezza（Phase 3 NORM，2025）响应65%，但每周给药，仍输频率。 但Viridian未稳赢： 1.跨研究比较不可靠：不同入组、基线、终点。重点看自身vs安慰剂、亚型重复、安全画像、偏好。 2.听力AE绕不开：虽低，但需监测可逆性、累积风险。监管/支付方关注高，尤其SC家庭化。 3.复视需完整解释：积极但非压倒性，TED多症状，不同步改善。 4.商业落地：payer支持家庭模式？首针监测？冷链/培训？价格/渠道竞争？剂型创新≠自动成功，但给谈判筹码。第七，更大视角：Viridian的价值是“给药工程学平台” Viridian不只TED药，而是验证“已证机制的下一代形态”：高效IV+SC低频，潜在复用其他免疫场景。在生物医药，稀缺的是优化已验证靶点、提升渗透率。Viridian证明：IGF-1R从输液到注射时代。结语：TED终局是“双路径分层”，Viridian或成定义者 TED市场不会“一药通吃”，而是医院IV（Tepezza/veligrotug）+便利SC（elegrobart）。Viridian卡双位，改变不止剂型，更是渗透逻辑。从2024 PK桥接到2026 REVEAL-2，链条完整：半衰期优、暴露桥接、安全可行、疗效显著。如果BLA Q1 2027顺利，TED从“输液时代”走向“低频注射时代”。临床医生，建议关注慢性患者筛查；研发人员，这套工程思维值得借鉴。所有观点基于Viridian官方（investors.viridiantherapeutics.com，2026.5.5）、ClinicalTrials.gov (NCT06625398/NCT06625411)、ENDO/ATA/Innovate TED 2024海报、PubMed (PMID:38012345等)、行业报告。欢迎留言讨论，非医疗建议，请咨询专业医师。关注老汤，下期聊更多黑马！ （数据来源：Viridian新闻稿、ClinicalTrials.gov、PubMed等。保持客观，如需治疗请咨询医生。）