第99.1展示文本
bicycle therapeutics报告最近的业务
进展
以及2024年第三季度财务结果
展示了肿瘤学领域更新的临床结果，包括Zelenectide Pevedotin单药物治疗的45%总体反应率（ORR），以及BT5528 6.5毫克/平方米单药物治疗的45% ORR。2 每两周单药物治疗，在转移性膀胱癌中都呈现出良好的疗效。
通过首次人体成像数据验证MT1-MMP作为新型癌症靶点的潜力，并概述了公司在该领域的策略
截至2024年9月30日，现金及现金等价物为89090万美元，不包括2024年10月收到的3170万英镑的英国研发税收抵免；预计财务支持将持续至2024年下半年7
2024年10月31日，英国剑桥和美国波士顿 - bicycle therapeutics公司（纳斯达克股票代码：BCYC）是一家药品公司，致力于开拓一种基于其专有的双环肽（Bicycle®技术的新型和不同类别的疗法。今天，该公司报告了截至2024年9月30日的第三季度的最新业务进展和财务结果。
在第三季度，我们在业务和管线方面继续取得了重大进展。在ESMO大会上，我们报告了我们临床阶段分子的更新数据，进一步支持它们具有令人期待的单药治疗反应率和不同的安全性概况。此外，上周我们分享了我们首个放射药物分子的激动人心的首次人体成像数据，验证了MT1-MMP作为一种新型癌症靶点的潜力，并提供了关于我们的Bicycle分子将放射性同位素输送至肿瘤的能力的重要信息。”Bicycle Therapeutics的首席执行官凯文·李博士说：“总的来说，我们相信这些数据展示了我们Bicycle技术平台的强大和广泛能力，我们期待在今年晚些时候提供更多更新。”
2024年第三季度及最近事件
| · | 宣布首份自行车放射性核素结合物（BRC）的人体成像数据®瞄准MT1-MMP并概述在下一代放射性药物中的领导策略。 |
| o | 2024年欧洲核医学协会大会上呈报的数据验证了MT1-MMP作为肿瘤治疗新靶点的潜力，展示了BRC临床前数据的可翻译性，并突显了Bicycle的潜力。®分子用于靶向放射性核素治疗。 |
| § | 德国癌症联盟在口头报告中分享了一位65岁男性的资料，他被诊断患有高级肺腺癌，这是非小细胞肺癌中最常见的一种类型，在肺部和淋巴结中经支气管超声内镜活检证实。两项扫描显示出多发淋巴结转移和胸骨处的骨转移。MT1-MMP成像显示示踪剂在肺部的原发肿瘤、淋巴结和骨转移处有摄取，与FDG成像一致。另外，MT1-MMP BRC示踪剂显示肾脏排泄，所有其他器官只显示微量示踪剂摄取。在早期时间点还观察到明显的成像对比。 |
| § | 在由bicycle therapeutics展示的电子海报中，临床前数据显示bicycle分子适用于将铟输送至肿瘤 ，为抑郁症、焦虑症和其他沉思性障碍提供了有前景的新疗法。 由于其具有的有利特性，包括特异性肿瘤摄取、迅速穿透肿瘤和快速肾脏排泄。此外，影像显示，BRCs的生物分布特性可以被优化，以保持高肿瘤摄取和保留，并显著减少肾脏水平。这些数据进一步积累了该公司在该领域发表的临床前数据，展示了bicycle分子有效输送各种放射性同位素，如镥和铅，至肿瘤。 |
| o | bicycle therapeutics在放射性药物领域的策略侧重于追求新颖的靶点，并选择最符合靶生物学和指示的同位素。根据这一策略，该公司选择了EphA2，一种在许多癌症中广泛表达的新型肿瘤抗原，作为其第二个BRC靶点，并与领先的同位素技术公司Eckert & Ziegler签署了一份意向书，达成协议供应一系列放射性同位素，并开发和生产BRC分子。 |
| · | 在2024年的欧洲医疗肿瘤学会议上，展示了整个肿瘤药物管线的最新临床结果。 |
| o | Zelenectide pevedotin（原名 BT8009） 是自行车毒素偶联物 (BTC)®) 靶向 Nectin-4 的分子，a 经过充分验证的肿瘤抗原。正在进行的评估 5 mg/m 的 1/2 期 Duravelo-1 试验的最新结果2 每周一次 对以前未接受过治疗的转移性尿路上皮癌 (muC) 患者使用泽来奈西特 pevedotin 单一疗法 enfortumab vedotin 在疗效可评估患者（n=38）中显示总缓解率（ORR）为45％，中位持续时间为 在确诊反应的患者中，反应时间为11.1个月（n=14）。Zelenectide pevedotin 继续表现出一种新兴的 差异化的安全性，尤其是在周围神经病变、皮肤反应和眼睛等相关不良事件方面 障碍。 |
全球Phase 2/3 Duravelo-2注册试验正在招募UC患者。计划到年底发布zelenectide pevedotin单药在其他肿瘤类型中的额外数据更新，以及与pembrolizumab联合用于一线UC治疗。
| o | BT5528 是一种针对肿瘤抗原EphA2的BTC分子，在历史上一直很难利用其他药物结合物法进行靶向治疗。正在进行的1/2期试验的更新结果评估了每周6.5 mg/m的BT5528单药治疗方案2 每两周6.5毫克2 在爱文思控股固体肿瘤晚期患者中，每周进行BT5528单药治疗，显示出新出现的差异化安全性和抗肿瘤活性，其中包括在剂量扩展队列（n=11）中接受6.5 mg/m的膀胱癌患者中有45%的ORR2 每两周接受6.5 mg/m的剂量。 |
bicycle therapeutics目前正在评估BT5528剂量为6.5毫克/平方米2每两周与尼伏单抗结合使用，预计结果将在2025年公布。
| o | BTC临床数据分析显示，接受zelenectide pevedotin或BT5528治疗的患者出现与治疗相关的外周神经病(TRPN)的发生率很低，主要为低级别。 在持续进行的1/2期研究中，223名患者中，zelenectide pevedotin治疗组中有28%的患者出现TRPN，BT5528治疗组中有19%的患者出现，几乎全部为低级别（1-2级）。其中一例3级事件(神经痛)报告了一例接受zelenectide pevedotin治疗的患者，在此之前接受了enfortumab vedotin治疗，而对于BT5528未观察到3-4级事件。 |
These data showing low rates of TRPN at primarily low severity with BTC molecules support the hypothesis that the antibody-drug construct may be a primary driver of peripheral neuropathy rather than monomethyl auristatin E (MMAE) toxicity as was previously believed.
| o | BT7480 is a Nectin-4 targeted CD137 agonist designed to overcome immune agonist toxicities and activate the immune system in Nectin-4 expressing tumors. Initial data from the Phase 1/2 dose escalation trial evaluating BT7480 in patients with advanced solid tumors showed an emerging differentiated safety and tolerability profile, with low rates of severe adverse events among 39 patients assigned to receive one of 10 different doses (0.002-3.5 mg/kg weekly). Preliminary biomarker analyses support BT7480 dual targeting of CD137 and Nectin-4 as demonstrated by enhanced immune cell activation, aligned with the proposed mechanism of action of BT7480. |
As the maximum tolerated dose for BT7480 has not yet been reached, Bicycle Therapeutics is continuing dose exploration in combination studies, starting with nivolumab.
| · | Promoted Zafar Qadir to Chief Legal Officer and General Counsel. Since joining Bicycle Therapeutics in April 2020, Mr. Qadir has managed critical responsibilities to support the company’s growth by leading the legal, compliance and intellectual property functions. Over the course of his career, Mr. Qadir has more than a decade of corporate, legal, intellectual property, regulatory and compliance experience and has played a pivotal role in Bicycle Therapeutics’ key partnerships and transactions. |
Third Quarter 2024 Financial Results
| · | Cash and cash equivalents were $890.9 million as of September 30, 2024, compared to $526.4 million as of December 31, 2023. The increase in cash and cash equivalents is primarily due to net proceeds from our PIPE financing in May 2024 and share option exercises, offset by the repayment of our debt facility with Hercules Capital, Inc. in July 2024 and cash used in operating activities. |
| · | Research and Development (R&D) expenses were $48.3 million for the three months ended September 30, 2024, compared to $39.9 million for the three months ended September 30, 2023. The increase in expense of $8.4 million was primarily due to increased clinical program expenses for zelenectide pevedotin development and increased personnel-related expenses, including incremental share-based compensation of $1.1 million, offset by decreased clinical program expenses for Bicycle Tumor-Targeted Immune Cell Agonist® molecule development, lower discovery, platform and other expenses, and higher U.K. R&D tax credits period over period. |
| · | General and administrative expenses were $18.3 million for the three months ended September 30, 2024, compared to $16.3 million for the three months ended September 30, 2023. The increase of $2.0 million was primarily due to increased personnel-related expenses, including incremental share-based compensation expense of $0.7 million. |
| · | Net loss was $50.8 million, or $(0.74) basic and diluted net loss per share, for the three months ended September 30, 2024, compared to net loss of $49.9 million, or $(1.26) basic and diluted net loss per share, for three months ended September 30, 2023. |
About Bicycle Therapeutics
Bicycle Therapeutics is a clinical-stage pharmaceutical company developing a novel class of medicines, referred to as Bicycle® molecules, for diseases that are underserved by existing therapeutics. Bicycle molecules are fully synthetic short peptides constrained with small molecule scaffolds to form two loops that stabilize their structural geometry. This constraint facilitates target binding with high affinity and selectivity, making Bicycle molecules attractive candidates for drug development. The company is evaluating zelenectide pevedotin (formerly BT8009), a Bicycle® Toxin Conjugate (BTC®) targeting Nectin-4, a well-validated tumor antigen; BT5528, a BTC molecule targeting EphA2, a historically undruggable target; and BT7480, a Bicycle Tumor-Targeted Immune Cell Agonist® (Bicycle TICA®) targeting Nectin-4 and agonizing CD137, in company-sponsored clinical trials. Additionally, the company is developing Bicycle Radionuclide Conjugates (BRC®) for radiopharmaceutical use and, through various partnerships, is exploring the use of Bicycle® technology to develop therapies for diseases beyond oncology.
Bicycle Therapeutics is headquartered in Cambridge, UK, with many key functions and members of its leadership team located in Cambridge, Mass. For more information, visit bicycletherapeutics.com.
Forward Looking Statements
This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Bicycle’s anticipated progress across its R&D pipeline and the advancement of its business and its product candidates, including zelenectide pevedotin, BT5528 and BT7480; the anticipated progression of Bicycle’s clinical trials and the timing of announcement of data from clinical trials and program updates for clinical candidates; the development of potential radiopharmaceutical product candidates; the use of Bicycle’s technology through various partnerships to develop potential therapies in diseases beyond oncology; and Bicycle’s expected financial runway. Bicycle may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in research and development and in the initiation, progress and completion of clinical trials and clinical development of Bicycle’s product candidates; the risk that Bicycle may not realize the intended benefits of its technology or partnerships; timing of results from clinical trials; whether the outcomes of preclinical studies will be predictive of clinical trial results; the risk that trials may have unsatisfactory outcomes; potential adverse effects arising from the testing or use of Bicycle’s product candidates; the risk that Bicycle’s projections regarding its expected cash runway are inaccurate or that its conduct of its business requires more cash than anticipated; and other important factors, any of which could cause Bicycle’s actual results to differ from those contained in the forward-looking statements, are described in greater detail in the section entitled “Risk Factors” in Bicycle’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on August 6, 2024, as well as in other filings Bicycle may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Bicycle expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as otherwise required by law.
Bicycle Therapeutics plc
Condensed Consolidated Statements of Operations and Comprehensive Loss
(In thousands, except share and per share data)
(Unaudited)
| Three Months Ended | Nine Months Ended | |||||||||||||||
| September 30, | September 30, | |||||||||||||||
| 2024 | 2023 | 2024 | 2023 | |||||||||||||
| Collaboration revenues | $ | 2,676 | $ | 5,352 | $ | 31,567 | $ | 21,645 | ||||||||
| Operating expenses: | ||||||||||||||||
| Research and development | 48,265 | 39,868 | 123,188 | 111,799 | ||||||||||||
| General and administrative | 18,257 | 16,281 | 50,588 | 45,557 | ||||||||||||
| Total operating expenses | 66,522 | 56,149 | 173,776 | 157,356 | ||||||||||||
| Loss from operations | (63,846 | ) | (50,797 | ) | (142,209 | ) | (135,711 | ) | ||||||||
| Other income (expense): | ||||||||||||||||
| Interest and other income | 10,583 | 3,985 | 23,981 | 7,726 | ||||||||||||
| Interest expense | (33 | ) | (814 | ) | (1,678 | ) | (2,443 | ) | ||||||||
| Loss on extinguishment of debt | (954 | ) | — | (954 | ) | — | ||||||||||
| Total other income, net | 9,596 | 3,171 | 21,349 | 5,283 | ||||||||||||
| Net loss before income tax provision | (54,250 | ) | (47,626 | ) | (120,860 | ) | (130,428 | ) | ||||||||
| (Benefit from) provision for income taxes | (3,448 | ) | 2,272 | (3,683 | ) | 1,137 | ||||||||||
| Net loss | $ | (50,802 | ) | $ | (49,898 | ) | $ | (117,177 | ) | $ | (131,565 | ) | ||||
| Net loss per share, basic and diluted | $ | (0.74 | ) | $ | (1.26 | ) | $ | (2.15 | ) | $ | (3.95 | ) | ||||
| Weighted average ordinary shares outstanding, basic and diluted | 68,988,858 | 39,576,467 | 54,566,490 | 33,291,701 | ||||||||||||
Condensed Consolidated Balance Sheets Data
(In thousands)
(Unaudited)
| September 30, | December 31, | |||||||
| 2024 | 2023 | |||||||
| Cash and cash equivalents | $ | 890,862 | $ | 526,423 | ||||
| Working capital | 909,789 | 492,331 | ||||||
| Total assets | 996,746 | 595,344 | ||||||
| Total shareholders’ equity | 831,032 | 370,932 | ||||||
Investors:
Stephanie Yao
SVP, Investor Relations and Corporate Communications
stephanie.yao@bicycletx.com
857-523-8544
Matthew DeYoung
Argot Partners
ir@bicycletx.com
212-600-1902
Media:
Jim O’Connell
Weber Shandwick
media@bicycletx.com
312-988-2343