Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q CENTESSA PHARMACEUTICALS PLC (Exact name of registrant as specified in its charter) England and Wales 98-1612294 (State or other jurisdiction of incorporation or organization) (Mark One) x QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 OR o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1 ...

Exhibit 99.1 • ORX750 Phase 2a CRYSTAL-1 study for the treatment of narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) on track with data expected in all three indications this year with first-in-class potential in NT2 and IH • ORX142 Phase 1 clinical trial for the treatment of select neurological and neurodegenerative disorders underway with data in acutely sleep-deprived healthy volunteers expected this year • ORX489 in IND-enabling studies for the treatment of neuropsychiatr ...

Pipeline and Milestones - Centessa Pharmaceuticals 专注于发现和开发针对患者的变革性药物[7, 50]。 - 公司预计在 2025 年实现 OX2R 激动剂管线的多个临床里程碑[7, 50]。 - ORX750 的 2a 期临床数据预计在 2025 年公布，针对嗜睡症 I 型 (NT1)、嗜睡症 II 型 (NT2) 和特发性嗜睡症 (IH) 患者[10]。 - ORX142 在急性睡眠剥夺的健康志愿者中的临床数据预计在 2025 年公布[10]。 - ORX489 正在推进 IND (新药研究申请) 支持性研究[10, 49]。 ORX750 and Market Opportunity - ORX750 是一种高效、选择性的 OX2R 激动剂，有潜力重新定义睡眠-觉醒障碍患者的标准治疗方法[21]。 - NT1、NT2 和 IH 代表着庞大的潜在患者群体，美国约有 62 万名患者[23, 25]。 - 在美国，大约有 27 万名 NT1、NT2 和 IH 患者被诊断和治疗[23, 25]。 ORX750 Clinical Data - 在一项研究中，2.5 毫克、3.5 毫克和 5.0 毫克剂量的 ORX750 在急性睡眠剥夺的健康志愿者中均产生了超过 30 分钟的 MWT LS 平均睡眠潜伏期[29]。 - ORX750 在 KSS 评分中显示出剂量依赖性的显著改善，与安慰剂相比，剂量 ≥ 2.5 毫克时具有显著性[32]。 - ORX750 显示出良好的安全性和耐受性[38]。

Core Viewpoint - Centessa Pharmaceuticals PLC (CNTA) has received a Zacks Rank 2 (Buy) upgrade, indicating a positive trend in earnings estimates that could enhance its stock price [1][4]. Earnings Estimates and Ratings - The Zacks rating system is based on changes in earnings estimates, which are tracked through the Zacks Consensus Estimate from sell-side analysts [2]. - A positive change in earnings estimates is a significant factor influencing stock price movements, making the Zacks rating system valuable for investors [3][5]. Impact of Institutional Investors - Institutional investors utilize earnings estimates to determine the fair value of stocks, leading to buying or selling actions that affect stock prices [5]. Business Improvement Indicators - Rising earnings estimates and the Zacks rating upgrade suggest an improvement in Centessa Pharmaceuticals' underlying business, which could lead to higher stock prices [6]. Importance of Earnings Estimate Revisions - Research indicates a strong correlation between earnings estimate revisions and near-term stock movements, highlighting the importance of tracking these revisions for investment decisions [7]. Zacks Rank System Performance - The Zacks Rank system categorizes stocks into five groups based on earnings estimates, with Zacks Rank 1 stocks historically generating an average annual return of +25% since 1988 [8]. Specific Earnings Estimates for Centessa Pharmaceuticals - Centessa Pharmaceuticals is projected to earn -$1.32 per share for the fiscal year ending December 2025, with no year-over-year change, but the Zacks Consensus Estimate has increased by 11.8% over the past three months [9]. Overall Rating System Characteristics - The Zacks rating system maintains a balanced distribution of "buy" and "sell" ratings across its universe of over 4,000 stocks, with only the top 20% receiving favorable ratings [10][11].

Core Viewpoint - Centessa Pharmaceuticals has received FDA clearance to initiate a Phase 1 clinical study of ORX142, a novel OX2R agonist aimed at treating neurological and neurodegenerative disorders, marking a significant milestone in the company's drug development pipeline [1][2]. Group 1: Clinical Development - The Phase 1 study will assess the safety, tolerability, and pharmacokinetics of ORX142 in healthy volunteers, including single-ascending doses (SAD) and multiple-ascending doses (MAD) [2]. - A placebo-controlled crossover pharmacodynamic assessment will be conducted using the Maintenance of Wakefulness Test (MWT) and Karolinska Sleepiness Scale (KSS) in acutely sleep-deprived subjects [2]. - Clinical data from the Phase 1 study is expected to be available within the year, which will aid in dose selection for future studies involving patients [2]. Group 2: OX2R Agonist Program - Centessa's OX2R agonist program includes multiple candidates: ORX750, ORX142, and ORX489, targeting various sleep-wake disorders and neuropsychiatric conditions [3]. - ORX750 is currently in a Phase 2a study for narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) [3]. - The orexin pathway is being targeted to address excessive daytime sleepiness (EDS), cognitive deficits, and fatigue associated with a range of neurological and neurodegenerative disorders [3]. Group 3: Company Overview - Centessa Pharmaceuticals is a clinical-stage pharmaceutical company focused on developing transformational medicines, particularly in the area of OX2R agonists [4]. - The company is also exploring an early-stage immuno-oncology program utilizing its novel LockBody technology platform [4].

Summary of Centessa Pharmaceuticals (CNTA) FY Conference Call - June 10, 2025 Company Overview - Centessa Pharmaceuticals has transitioned to focus on orexin receptor-targeted therapies, particularly the orexin 2 receptor, which is seen as a potentially transformational class of drugs for patients with sleep disorders and neuropsychiatric conditions [3][4][5] Core Industry Insights - The market opportunity for orexin agonists in the rare hypersomnia space is estimated to exceed $15 billion, with potential applications extending to excessive daytime sleepiness and other neuropsychiatric conditions [4][41] - The company has a robust portfolio of orexin agonists and plans to present data for narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) in 2025 [5][64] Key Points on Drug Development - Centessa aims to differentiate itself through a best-in-class approach, focusing on tolerability and efficacy, with a proprietary crystal structure aiding in the development of their drug candidates [7][8] - The company has conducted extensive healthy volunteer studies, which have informed dosing strategies for patient populations [9][10] - The mean wakefulness time (MWT) is emphasized as a critical predictor of drug efficacy, with a target of achieving significant MWT improvements throughout the day [13][15][16] Phase II Clinical Trial Design - The Phase II trial is designed to establish a therapeutic index and allow for flexible dosing based on patient needs, with a focus on real-time drug development [18][19][20] - The trial will include a minimum number of patients to ensure statistical significance, with the potential to increase patient numbers as needed [19][20] - Inclusion and exclusion criteria are carefully defined to ensure a homogeneous patient population, particularly for NT2 and IH [27][28] Competitive Landscape - The company aims to be best in class among competitors, with a focus on the unique dosing flexibility and tolerability of its drugs compared to existing treatments [36][37][46] - The market for orexin agonists is expected to be large, with multiple players potentially sharing the opportunity, but Centessa is positioning itself to capture significant market share [46][47] Market Potential and Commercial Strategy - The potential market for NT1 alone is estimated at $5-6 billion, with the overall opportunity in the orexin agonist space being significantly larger [42][43] - Centessa is conducting extensive market research to validate its estimates and understand physician and patient needs [51][52] Future Developments - The company has a cash runway extending into mid-2027, supporting multiple clinical milestones and data releases for its drug candidates [64][65] - Upcoming data releases for NT1, NT2, and IH are anticipated, with the possibility of presenting data for all three indications simultaneously or in subsets [66][67] Conclusion - Centessa Pharmaceuticals is strategically positioned in the orexin agonist market, with a strong focus on innovative drug development, robust clinical trial design, and a clear understanding of market dynamics and patient needs. The company is poised for significant growth as it advances its drug candidates through clinical trials and prepares for commercialization.

Summary of Centessa Pharmaceuticals (CNTA) Conference Call Company Overview - **Company**: Centessa Pharmaceuticals (CNTA) - **Focus**: Orexin program, specifically ORX750, an orexin agonist for treating narcolepsy and idiopathic hypersomnia Key Insights on Orexin Space - **Exciting Year Ahead**: Centessa anticipates a data-rich year with multiple catalyst events, including Phase II data disclosures for narcolepsy type one, type two, and idiopathic hypersomnia with ORX750, which is considered the most potent and selective orexin agonist in clinical development [2][4] - **First in Class Opportunity**: The company aims for a first-in-class opportunity in narcolepsy type two and idiopathic hypersomnia, with a best-in-class profile characterized by rapid onset of action, potential for QT dosing, linear pharmacokinetics (PK), and flexible dosing [2][4] Phase II Study Design - **Innovative Design**: The Phase II study allows for dose selection during the study based on real-time data, enabling optimal dosing and flexibility for patients [2][3] - **Efficacy Data**: Preliminary data from sleep-deprived healthy volunteers showed significant efficacy, with patients on ORX750 maintaining wakefulness significantly longer than those on placebo [7][8] Safety and Tolerability - **High Tolerability**: The drug class is reported to be extremely well tolerated, with minimal on-target adverse events (AEs) such as insomnia and polyuria [15][16] - **Liver Toxicity Concerns**: Centessa emphasizes that liver toxicity is molecule-specific and not an on-target effect, focusing on developing molecules with a favorable metabolic profile to mitigate risks [20] Market Opportunity - **Large Patient Population**: The company has revised epidemiological numbers, identifying approximately 50,000 diagnosed and treated narcolepsy type one patients, 100,000 in type two, and 120,000 in idiopathic hypersomnia, indicating a substantial market opportunity [24][25] - **Potential for Multiple Agonists**: There is potential for more than one orexin agonist in the market, given the large patient population and unmet clinical needs [25] Future Directions - **Expansion into Other Indications**: Centessa plans to explore orexin agonists in neurodegenerative and psychiatric disorders, such as Parkinson's disease and major depressive disorder, where excessive daytime sleepiness is prevalent [36][37] - **Partnership Opportunities**: While currently fully financed to execute clinical development plans, the company remains open to partnerships for indication expansion in the future [38] Conclusion - **Transformational Potential**: The orexin agonist class, particularly ORX750, is positioned to significantly impact the treatment landscape for narcolepsy and other disorders characterized by excessive daytime sleepiness, with a strong focus on patient needs and flexible dosing strategies [36][37]

Centessa Pharmaceuticals PLC Sponsored ADR (CNTA) closed the last trading session at $13.36, gaining 11.2% over the past four weeks, but there could be plenty of upside left in the stock if short-term price targets set by Wall Street analysts are any guide. The mean price target of $31.90 indicates a 138.8% upside potential.The average comprises 10 short-term price targets ranging from a low of $27 to a high of $38, with a standard deviation of $4.01. While the lowest estimate indicates an increase of 102.1 ...

Financial Performance - Centessa Pharmaceuticals reported a license revenue of $15.0 million for the three months ended March 31, 2025, from a license agreement with Genmab[119]. - The net loss for the three months ended March 31, 2025, was $26.1 million, compared to a net loss of $38.0 million for the same period in 2024[118]. - Interest income rose to $7.9 million in Q1 2025, compared to $2.6 million in Q1 2024, indicating improved cash management[118]. - General and administrative expenses decreased to $12.3 million in Q1 2025 from $13.4 million in Q1 2024, primarily due to lower share-based compensation and consulting fees[121]. - Net cash used in operating activities was $57.2 million in Q1 2025, compared to $37.3 million in Q1 2024, reflecting a net loss of $26.1 million[134][135]. - Net cash used in investing activities was $222.4 million in Q1 2025, primarily due to investments in fixed income, compared to a net cash inflow of $16.8 million in Q1 2024[136]. Research and Development - Research and development expenses increased to $33.4 million in Q1 2025, up from $22.7 million in Q1 2024, reflecting a significant investment in clinical programs[118]. - Research and development expenses for Q1 2025 were $33.4 million, up from $22.7 million in Q1 2024, reflecting a $15.4 million increase in costs for the OX2R agonist program[120]. - Centessa Pharmaceuticals is advancing its OX2R agonist program, with ORX750 currently in a Phase 2a study for narcolepsy and other sleep disorders[96][98]. - The company plans to initiate first-in-human studies for ORX142 in 2025, targeting neurological and neurodegenerative disorders[99]. - Centessa discontinued the clinical development of LB101, a LockBody candidate, based on clinical data, while continuing to evaluate the LockBody platform[101]. Funding and Cash Management - The company had cash, cash equivalents, and investments totaling $424.9 million as of March 31, 2025, expected to fund operations into mid-2027[104]. - The company entered into a loan agreement for up to $200 million, receiving $110 million initially, with additional funds available upon achieving certain milestones[126][127]. - The company sold 372,538 ordinary shares under the ATM program in Q1 2025, generating net proceeds of $6.1 million, totaling approximately $36.6 million since the program's inception[131]. - Future funding requirements are expected to increase significantly due to ongoing product development and commercialization efforts[138][139]. Company Classification and Reporting - The company is classified as an emerging growth company, allowing it to delay the adoption of new accounting standards[143]. - The company will remain an emerging growth company until it achieves total annual gross revenues of $1.235 billion or more[144]. - The company is classified as a "smaller reporting company" under the Securities Exchange Act of 1934, allowing it to present only the two most recent fiscal years of audited financial statements in its Annual Report[145]. - As a smaller reporting company, the company has reduced disclosure obligations regarding executive compensation[145]. - The company is not required to provide qualitative and quantitative disclosures about market risk under SEC rules and regulations[146]. License Agreements - A license agreement with Genmab allows access to the LockBody technology platform for research against up to three targets, with Genmab conducting all related R&D activities[102]. - The company expects to incur significant expenses and operating losses as it continues to develop its product candidates and expand its research activities[104].

Exhibit 99.1 Centessa Pharmaceuticals Reports Financial Results and Business Highlights for the First Quarter of 2025 Advancing a broad, potential best-in-class orexin receptor 2 (OX2R) agonist franchise, with key data readouts expected this year BOSTON and LONDON, May 14, 2025 -- Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage pharmaceutical company, today reported financial results and business highlights for the first quarter ended March 31, 2025. "This was a productive quarter for Centessa ...