APG-222

Positive interim results from APG777 Phase 1 healthy volunteer clinical trial exceeded objectives withapproximately 75-day half-life which supports the potential for higher exposures leading to potential for improved clinical responses in induction than currently available biologic therapies and the potential for maintenance dosing of every 3- or 6-months APG777 Phase 1 interim data support advancement of a randomized, placebo-controlled Phase 2 clinical trial in patients with moderate-to-severe atopic dermatitis in 1H 2024 ahead of schedule Phase 1 healthy volunteer clinical trial set to start ahead of schedule for APG808, a subcutaneous extended half-life antibody targeting IL-4Rα, following receipt of regulatory clearance in February Total cash of $395.5 million at year end 2023 with expected cash runway into 4Q 2026 SAN FRANCISCO and WALTHAM, Mass., March 05, 2024 (GLOBE NEWSWIRE) -- Apogee Therapeutics, Inc. (Nasdaq: APGE), a clinical-stage biotechnology company advancing differentiated biologics for the treatment of atopic dermatitis (AD), chronic obstructive pulmonary disease (COPD), asthma and other inflammatory and immunology (I&I) indications, today reported pipeline highlights and fourth quarter and full year 2023 financial results. “2023 was a momentous year for Apogee with the completion of a successful IPO, initiation of our first clinical program of APG777 in healthy volunteers and the nomination of our second pipeline candidate, APG808,” said Michael Henderson, M.D., Chief Executive Officer of Apogee. “Our momentum and track record of execution have continued in 2024, and we were thrilled to disclose positive interim results from our Phase 1 trial of APG777 today, which demonstrated a favorable safety pro exceeded our trial objectives on both pharmacokinetics and pharmacodynamics. This data readout is a key risk-reducing milestone for our APG777 program and pipeline and supports a path forward into a Phase 2 trial for APG777 in patients with AD in the first half of this year. Looking ahead to the rest of the year, we continue to make progress with APG808, for which we are set to start a Phase 1 healthy volunteer clinical trial ahead of schedule while advancing our earlier programs, APG990 and APG222. With each of our programs, we have the potential to reshape the standard of care with potential best-in-class or first-in-class therapeutic candidates for I&I diseases.” Pipeline Highlights and Upcoming Milestones Positive, interim Phase 1 results for APG777 exceeded trial objectives and delivered ahead of schedule: APG777 is a novel, subcutaneous (SQ) extended half-life monoclonal antibody targeting IL-13 – a critical cytokine in inflammation and a primary driver of AD. Today, the company reported positive interim results in the Phase 1 first-in-human study of APG777, designed to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single-ascending and multiple-ascending doses of APG777 in healthy volunteers. Key findings from the study include: Potentially best-in-class PK profile, including a half-life of approximately 75 days, supporting: Testing higher exposures of drug in induction to potentially achieve improved clinical responses Testing of maintenance dosing of every 3- or 6-months, representing 2-4 injections per year compared to the current treatment paradigm of 13-26 injections per year Single doses of APG777 showed deep and sustained effect on key AD biomarkers pSTAT6 and TARC for approximately 3 months (longest follow-up available with inhibition still ongoing at the time of the data cut APG777 was well tolerated across all dose groups with a favorable safety pro with the anti-IL-13 class Based on these data, Apogee plans to initiate a randomized, placebo-controlled Phase 2 clinical trial in patients with moderate-to-severe AD in the first half of 2024; modeled induction and maintenance dosing for the Phase 2 trial suggests APG777 could reach exposures approximately 30-40% greater than lebrikizumab in induction and potentially enable every 3- or 6- month maintenance dosing 16-week proof-of-concept data from this Phase 2 trial is expected in second half of 2025 Apogee also plans to evaluate APG777 in expansion indications including initiating a Phase 2 trial in asthma in 2025 Phase 1 APG808 healthy volunteer clinical trial set to start ahead of schedule: Apogee’s second program, APG808, is novel, SQ extended half-life mAb targeting IL-4Rα, a target with clinical validation across eight Type 2 allergic diseases. APG808 has similar binding and femtomolar affinity for IL-4Rα as compared to a first generation mAb, DUPIXENT, and has demonstrated similar inhibition to DUPIXENT across three in vitro assays which measure downstream functional inhibition of the IL-13/IL-4 pathway (pSTAT6 induction, inhibition of TF-1 proliferation, and inhibition of TARC secretion). An APG808 Phase 1 healthy volunteer clinical trial is expected to start ahead of schedule following receipt of regulatory clearance in February and will be followed by a potential Phase 1b trial in asthma and a Phase 2 trial in COPD (pending data from the Phase 1 trial). Key milestones in 2024 and 2025 include: Interim Phase 1 PK and safety in healthy volunteers expected in 2H 2024, ahead of prior guidance Initial proof-of-concept data in asthma expected 1H 2025 Proof-of-concept clinical trial in patients with COPD expected to initiate in 2025, pending positive data from Phase 1 trial and regulatory clearance Early-stage programs progressing to candidate selection: Apogee’s earlier-stage programs, APG990 and APG222, utilize advanced antibody engineering to target OX40L and both IL-13 and OX40L, respectively, and are initially being developed for the treatment of AD. OX40L is located further upstream in the inflammatory pathway than IL-13 or IL-4Rα and targeting it could potentially have broader impact on the inflammatory cascade. With current approved biologics only targeting two mechanisms of action (IL-13 and IL4Rα) in AD, OX40L could represent another therapeutic option for patients, especially the portion of patients who do not benefit from currently available treatments. Candidate nomination for APG990 anticipated in 2024 and Phase 1 initiation in healthy volunteers in 2025 Apogee plans to provide more detailed updates on its earlier pipeline programs and combination strategy in an R&D Day in Q4 2024 to support its vision of future I&I therapeutics Fourth Quarter and Full Year 2023 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $395.5 million as of December 31, 2023, compared to $151.9 million as of December 31, 2022. Based on current operating plans, Apogee expects its existing cash, cash equivalents and marketable securities will enable the company to fund its operating expenses into 4Q 2026. R&D Expenses: Research and development (R&D) expenses were $29.0 million for the quarter ended December 31, 2023, and $68.4 million for the year ended December 31, 2023, compared to $12.2 million for the quarter ended December 31, 2022, and $27.8 million for the period from February 4, 2022 (inception) to December 31, 2022. R&D expenses increased primarily due to further development of Apogee’s APG777 and APG808 programs and advancement of its pipeline, as well as increases in personnel costs, including equity-based compensation expense, associated with the growth of its R&D team. G&A Expenses: General and administrative (G&A) expenses were $8.2 million for the quarter ended December 31, 2023, and $24.6 million for the year ended December 31, 2023, compared to $1.9 million for the quarter ended December 31, 2022, and $2.9 million for the period from February 4, 2022 (inception) to December 31, 2022. G&A expenses increased primarily due to increases in personnel costs, including equity-based compensation, and legal and professional services, all of which were the result of the expansion of Apogee’s operations to support the growth in its business and the cost of operating as a public company. Net Loss: Net loss was $31.7 million for the quarter ended December 31, 2023, and $84.0 million for the year ended December 31, 2023, compared to a net loss of $14.0 million for the quarter ended December 31, 2022 and $39.8 million for the period from February 4, 2022 (inception) to December 31, 2022. Net loss increased primarily as a result of higher R&D and G&A operating expenses as described above, partially offset by higher interest income. About Apogee Apogee Therapeutics is a clinical-stage biotechnology company seeking to develop differentiated biologics for the treatment of atopic dermatitis (AD), chronic obstructive pulmonary disease (COPD), asthma and other inflammatory and immunology indications with high unmet need. Apogee’s antibody programs are designed to overcome limitations of existing therapies by targeting well-established mechanisms of action and incorporating advanced antibody engineering to optimize half-life and other properties. The company’s two most advanced programs are APG777 and APG808, which are being initially developed for the treatment of AD and COPD, respectively. Based on a broad pipeline and depth of expertise, the company believes it can deliver value and meaningful benefit to patients underserved by today’s standard of care. For more information, please visit . Forward Looking Statements Certain statements in this press release may constitute “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, statements regarding: the efficacy, safety, tolerability, PK and PD pro APG777, the potential dosing regimen of APG777, the potential superiority of APG777 compared to current therapies, Apogee’s expectations regarding plans for Apogee’s current and future product candidates and programs, Apogee’s plans for Apogee’s current and future clinical trials, including a Phase 2 trial for APG777, Apogee’s plans for clinical trial design, the anticipated timing of the initiation of and results from Apogee’s clinical trials, including data from Apogee’s Phase 2 trial of APG777, the potential clinical benefit and half-life of APG777, APG808, APG990, APG222 and any other potential programs, Apogee’s expected timing for future pipeline updates and expectations regarding the time period over which Apogee’s capital resources will be sufficient to fund Apogee’s anticipated operations. Words such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “develop,” “plan” or the negative of these terms, and similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. While Apogee believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to the company on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties (including, without limitation, those set forth in Apogee’s filings with the U.S. Securities and Exchange Commission (the SEC)), many of which are beyond the company’s control and subject to change. Actual results could be materially different. Risks and uncertainties include: global macroeconomic conditions and related volatility, expectations regarding the initiation, progress, and expected results of Apogee’s preclinical studies, clinical trials and research and development programs; expectations regarding the timing, completion and outcome of Apogee’s clinical trials; the unpredictable relationship between preclinical study results and clinical study results; the timing or likelihood of regulatory filings and approvals; liquidity and capital resources; and other risks and uncertainties identified in Apogee’s Quarterly Report on 10-Q for the quarterly period ended September 30, 2023, filed with the SEC on November 13, 2023, and subsequent disclosure documents we may the SEC. Apogee claims the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. Apogee expressly disclaims any obligation to update or alter any statements whether as a result of new information, future events or otherwise, except as required by law. APOGEE THERAPEUTICS, INC. CONSOLIDATED BALANCE SHEETS (In thousands, except unit/share data) DECEMBER 31, DECEMBER 31, 2023 2022 Assets Current assets: Cash and cash equivalents $ 118,316 $ 151,890 Marketable securities 277,143 — Prepaid expenses and other current assets 2,950 165 Total current assets 398,409 152,055 Property and equipment, net 377 — Right-of-use asset, net 2,217 — Other non-current assets 401 — Total assets $ 401,404 $ 152,055 Liabilities, preferred units and stockholders' equity/members’ deficit Current liabilities: Accounts payable $ 2,143 $ 418 Lease liability 1,101 — Accrued expenses 17,314 9,562 Total current liabilities 20,558 9,980 Long-term liabilities: Lease liability, net of current 933 — Total liabilities 21,491 9,980 Commitments and contingencies (Note 9) Series A Preferred Units; no units authorized, issued and outstanding at December 31, 2023; 20,000,000 units authorized, issued and outstanding as of December 31, 2022 — 28,971 Series B Preferred Units; no units authorized, issued and outstanding at December 31, 2023; 45,089,212 units authorized, issued and outstanding as of December 31, 2022 — 148,496 Stockholders’ equity/members’ deficit: Common Units; no units authorized, issued and outstanding at December 31, 2023; 5,000,000 units authorized, issued and outstanding as of December 31, 2022 — 2,251 Incentive Units; no units authorized, issued and outstanding at December 31, 2023; 12,412,473 units authorized, 9,648,374 issued and 1,625,086 outstanding as of December 31, 2022 — 2,142 Preferred Stock; 10,000,000 authorized, $0.00001 par value, no shares issued and outstanding at December 31, 2023; No shares authorized, issued and outstanding at December 31, 2022 — — Common Stock; 400,000,000 authorized, $0.00001 par value, 50,655,671 issued and 48,338,769 outstanding as of December 31, 2023; No shares authorized, issued and outstanding at December 31, 2022 — — Additional paid-in capital 503,354 — Accumulated other comprehensive income 329 — Accumulated deficit (123,770 ) (39,785 ) Total stockholders’ equity/members’ deficit 379,913 (35,392 ) Total liabilities, preferred units and stockholders’ equity/members’ deficit $ 401,404 $ 152,055 APOGEE THERAPEUTICS, INC. CONSOLIDATED STATEMENTS OF OPERATIONS (In thousands) PERIOD FROM YEAR ENDED FEBRUARY 4, 2022 DECEMBER 31, (INCEPTION) TO 2023 DECEMBER 31, 2022 Operating expenses: Research and development $ 68,424 $ 27,786 General and administrative 24,579 2,941 Total operating expenses 93,003 30,727 Loss from operations (93,003 ) (30,727 ) Other income (expense), net: Interest income, net 9,018 92 Other financing expense, net: — (9,150 ) Total other income (expense), net 9,018 (9,058 ) Net loss $ (83,985 ) $ (39,785 ) Investor Contact: Noel Kurdi VP, Investor Relations Apogee Therapeutics Noel.kurdi@apogeetherapeutics.com Media Contact: Dan Budwick 1AB dan@1abmedia.com

关注并星标CPHI制药在线    IL-13是一种免疫调节细胞因子，主要由活化的Th2细胞分泌。此外，D4+T细胞、CD8+T细胞、肥大细胞、嗜碱性粒细胞、嗜酸性粒细胞和NK细胞也可分泌IL-13。IL-13对单核巨噬细胞、B淋巴细胞、NK细胞和血管内皮细胞等具有多种生物学作用，是机体免疫反应的调节介质。       IL-13受体包括IL-13 Rα2非信号受体和II型受体两类。II型受体是由IL-4 Rα和IL-13 Rα1组成的受体复合体，其中IL-4 Rα结合IL-4，IL-13 Rα1结合IL-13，不过IL-4对IL-4 Rα的结合亲和力明显高于IL-13对IL-13 Rα1的亲和力。IL-4/IL-13与II型受体结合，会激活下游JAK1或JAK2/TYK2、STAT6、STAT3和STAT1，发生STAT二聚化和核易位，随后激活基因转录。而且，IL-13还与细胞表面的IL-13 Rα2非信号亚基结合。IL-13 Rα2被认为是II型受体的抑制性的亚单位，其作用是充当IL-13的“诱饵”受体。       研究发现，IL-13和IL-4是诱导和维持2型炎症反应的关键细胞因子，与多种特应性疾病如特异性皮炎（AD）、哮喘和慢性鼻窦炎伴鼻息肉病（CSwNP）等有关。正常情况下，IL-13和IL-4受体亚基在动态平衡条件下低水平表达。而且，IL-13、IL-4受体还在乳腺癌、淋巴瘤等肿瘤细胞表面表达上调。       全球仅批准一款IL-13靶向药       目前，全球针对IL-13靶点已开发出多款新药，其中仅LEO Pharma的Tralokinumab获批上市。Tralokinumab是一款靶向IL-13的全人IgG4单克隆抗体，通过高亲和力特异性结合IL-13，阻断IL-13与其受体的相互作用以及下游IL-13信号传导。Tralokinumab最初由阿斯利康开发。2016年，LEO Pharma与阿斯利康达成协议，获得该药全球开发权益。       2021年6月，Tralokinumab在欧盟被批准用于治疗适合接受全身治疗的中重度特应性皮炎(AD)患者，商品名为Adtralza。2021年12月，Tralokinumab在美国被批准用于治疗18岁及以上、无法通过局部处方疗法充分控制或治疗的中重度AD成人患者，商品名为Adbry。2022年10月，Adtralza被欧盟委员会(EC)批准扩大适应症人群，用于12至17岁中重度特AD青少年患者。       礼来Lebrikizumab惨遭FDA拒批       目前全球还有多款在研IL-13靶向药（详见下表），其中礼来的Lebrikizumab进展相对较快，已经申报上市。Lebrikizumab是一种新型单克隆抗体，通过高选择性结合IL-13，特异性阻止IL-13Rα1/IL-4Rα异二聚体复合物的形成和随后的信号传导，从而抑制 IL-13 在靶向治疗中的生物学效应。       值得一提的是，Lebrikizumab几经易主，其最初由Tanox开发，2007年罗氏通过收购Tanox获得该药，2017年罗氏将该药全球权益转让给Dermira，2020年礼来通过收购Dermira获得该药，不过该药的欧洲权益于2019年授权给了Almirall。       不过，Lebrikizumab在欧盟和美国有着完全不同的遭遇。今年9月，欧洲药品管理局（EMA）人用药品委员会（CHMP）建议批准Lebrikizumab用于治疗适合接受全身治疗的中重度AD成人和青少年患者。而在美国，FDA于今年10月拒绝批准该药用于治疗中重度AD患者。不过FDA拒绝批准并不是因为Lebrikizumab的疗效和安全性问题，而且因为在检查中发现了第三方合同生产组织的问题。       IL-13靶向药靶点多样       除了Tralokinumab和Lebrikizumab，IL-13靶向药Cendakimab进展也较快，目前处于3期临床。Cendakimab是一种人源化、高亲和力的IL-13单克隆抗体，通过结合IL-13配体，抑制配体与IL-13Ra1和IL-13Ra2亚基结合，从而起到抗炎和抗纤维化作用，被开发用于治疗嗜酸性粒细胞性食管炎（EoE）、嗜酸细胞性胃肠炎(EG)、特应性皮炎、湿疹等。       已完成的一项1期研究表明，Cendakimab在健康受试者以及轻度至中度持续性哮喘患者中具有良好的耐受性，并支持单剂量静脉注射和多次皮下注射。而Cendakimab治疗嗜酸性粒细胞性食管炎（EoE）的2期临床研究结果显示：相比于安慰剂组，Cendakimab组患者的嗜酸性粒细胞计数显著减少（P<0.0001）。       Cendakimab也多次易主，其最初由艾伯维开发，2013年Receptos（百时美施贵宝子公司）与艾伯维签订合作协议共同开发Cendakimab。2015年Celgene斥资72亿美元收购Receptos，2019年百时美施贵宝通过收购Celgene将Cendakimab纳入囊中。       在国内，Cendakimab于2022年10月在国内获批临床，单药或联合外用皮质类固醇，用于治疗对外用处方药控制不佳或不建议使用外用处方药的成人和12岁及以上青少年的中重AD患者。       Apogee Therapeutics公司有两款IL-13靶向药，其中APG777是一种靶向IL-13的SQ（皮下）延长半衰期单克隆抗体(mAb)。在对非人灵长类动物（NHP）（食蟹猴）中，APG777在抑制IL-13信号传导方面与礼来的lebrikizumab有相同或更好的效力。APG777的静脉注射（IV）和SQ制剂均显示出明显比lebrikizumab更长的半衰期。       而APG222是一种针对IL-13和OX40L的延长半衰期SQ抗体，可以双重降低OX40L信号传导，有助于重新平衡免疫系统，减少免疫细胞分化和细胞因子释放，并进一步降低IL-13，从而减少免疫信号传导。       此外，目前全球还有多款在研IL-13靶向药，这些药物中多款药物作用靶点比较多样，如辉瑞的三抗PF-07275315和PF-07264660、赛诺菲双抗Romilkimab。       总结       整体来看，IL-13靶向药主要被开发用于治疗炎性疾病，尤其是特应性皮炎（AD）。Tralokinumab作为目前唯一获批上市的IL-13靶向药，已被批准用于治疗12岁及以上中重度AD患者。礼来的Lebrikizumab作为处于第二梯队的IL-13靶向药，但却在美国惨遭拒批。此外，目前全球还有多款在研IL-13靶向药，期待未来有更多的IL-13靶向药获批，造福广大炎性疾病患者。扫码参与制药在线周年庆游园会来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~