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]

Group 1 - Centessa Pharmaceuticals PLC (CNTA) closed at $13.36, with an 11.2% gain over the past four weeks, and analysts set a mean price target of $31.90, indicating a potential upside of 138.8% [1] - The average of 10 short-term price targets ranges from a low of $27 to a high of $38, with a standard deviation of $4.01, suggesting a high degree of agreement among analysts [2] - The Zacks Consensus Estimate for the current year has increased by 10.4% over the past month, with five estimates going higher and no negative revisions [12] Group 2 - Analysts show strong agreement in revising earnings estimates higher, which correlates with potential stock price movements, indicating a legitimate reason for expecting an upside in CNTA [11] - CNTA holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates, suggesting a strong potential for near-term upside [13] - While the consensus price target may not be entirely reliable, the direction it implies appears to be a good guide for potential price movement [13]

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 ...

Core Insights - Centessa Pharmaceuticals reported a productive first quarter in 2025, highlighting progress in its OX2R agonist pipeline, particularly ORX750 for treating narcolepsy and other sleep disorders [2][3] Financial Performance - The company reported a net loss of $26.1 million for Q1 2025, an improvement from a net loss of $38.0 million in Q1 2024 [10] - Research and Development (R&D) expenses increased to $33.4 million in Q1 2025 from $22.7 million in Q1 2024 [6][10] - General and Administrative (G&A) expenses decreased to $12.3 million in Q1 2025 from $13.4 million in Q1 2024 [10] - Cash, cash equivalents, and investments totaled $424.9 million as of March 31, 2025, expected to fund operations into mid-2027 [6] Pipeline Developments - ORX750 is currently in the Phase 2a CRYSTAL-1 study for NT1, NT2, and IH, with data expected in 2025 [5][6] - ORX142 is on track to initiate first-in-human studies for neurological disorders, with clinical data planned for this year [5][6] - ORX489 is advancing in IND-enabling studies for neuropsychiatric disorders [5] Recent Highlights - Data from the Phase 1 study of ORX750 were presented at the American Academy of Neurology Annual Meeting, showing sustained effects in sleep latency and sleepiness scores compared to placebo [3] - The company aims to execute its pipeline efficiently, with multiple data readouts anticipated this year [2][5]

Operational Challenges - The company has 77 full-time equivalent employees as of March 1, 2025, which may limit its operational capabilities and ability to develop and commercialize programs [198]. - The company implemented a corporate consolidation of its U.S. and UK businesses in mid-2023 to simplify operations and improve efficiency [196]. - The company may face challenges in integrating the operations of its Centessa Subsidiaries, which could expose it to operational and financial risks [194]. - The company may need to divert management's attention to growth activities, impacting day-to-day operations [198]. - The company faces conflicts of interest due to overlapping roles of its officers in both the parent company and its subsidiaries [203]. Financial Position - The company has incurred significant net losses since inception and expects to continue incurring losses for the foreseeable future, with no revenue generated from product sales to date [208]. - As of December 31, 2024, the company had $482.2 million in cash and cash equivalents, expected to fund operations into mid-2027 [217]. - The company anticipates needing substantial additional funds to advance the development of its product candidates, with plans to raise up to $125 million through an Open Market Sale Agreement [216]. - The company faces risks related to its financial position, including the need for additional capital and potential dilution of shareholder value if equity financing is pursued [221][222]. - The company has a limited operating history, making it difficult for investors to evaluate its business and prospects [211]. Product Development and Commercialization Risks - The company may not be successful in developing and commercializing product candidates, which could significantly harm its financial position and adversely affect stock price [189]. - The company has historically relied on independent organizations for regulatory approval and clinical trial management, which presents risks if these services are not available [199]. - A large proportion of the company's value may reside in a limited number of programs, making it vulnerable to adverse developments in those areas [192]. - The company may not be able to attract or execute transactions with subject-matter experts due to its unique asset-centric approach [190]. - The company has terminated several clinical development programs, including the lixivaptan program for ADPKD and the LB101 program for advanced solid tumors, based on strategic evaluations of clinical data [206][207]. Regulatory and Clinical Development Challenges - The company faces risks related to clinical development, including potential delays and failures in obtaining regulatory approvals [237]. - The marketing approval process is expensive and time-consuming, with no guarantee of success, potentially harming the commercial prospects of product candidates [254]. - The company plans to seek initial marketing approval in the United States and major markets in the EU and the UK, but may face challenges in patient enrollment [259]. - Regulatory authorities may impose additional requirements or restrictions that could limit the commercial viability of approved products [252]. - The company is dependent on third parties for accurate data generation and reporting from preclinical studies and clinical trials, which could adversely affect clinical development and commercialization if not compliant [261]. Manufacturing and Supply Chain Risks - Manufacturing processes are complex and may face disruptions due to various factors, including equipment malfunctions and raw material shortages [310]. - The company relies on third-party manufacturers for product candidates, exposing it to risks such as supply chain shortages and quality issues [316]. - The company has not yet manufactured its product candidates on a commercial scale and may face challenges in negotiating favorable terms with outside vendors [316]. - The active pharmaceutical ingredients (API) for certain product candidates are supplied by single-source suppliers, and the loss of any of these suppliers could significantly harm the business [320]. - The company faces risks related to the availability of non-human primates (NHPs) for research, which have been constrained due to global supply issues, leading to increased costs [326]. Intellectual Property Risks - The company must obtain and maintain sufficient patent protection for its product candidates, as failure to do so could allow competitors to develop similar products [327]. - The patent prosecution process is expensive and time-consuming, and the company may not be able to secure necessary patent protections in a timely manner [330]. - The company cannot assure that its product candidates do not infringe on existing patents, increasing the risk of litigation as the biotechnology and pharmaceutical industries expand [336]. - The company may face substantial damages and litigation expenses if found to infringe third-party patents, which could significantly harm its business [341]. - The expiration of patents could open the company to competition from generic medications, adversely affecting its business [366]. Market and Competitive Landscape - The biotechnology and pharmaceutical industries are characterized by rapid technological changes and significant competition, which may hinder the company's ability to market its product candidates effectively [274]. - The potential market for product candidates may be smaller than estimated, adversely affecting financial viability and revenue [384]. - Market acceptance of product candidates will depend on efficacy, safety, cost relative to alternatives, and physician willingness to prescribe [381]. - The company currently has no sales and marketing organization, which could hinder the ability to generate product revenue [386]. - Efforts to educate the medical community on product benefits may require significant resources and may not be successful [387].

Financial Performance - Centessa Pharmaceuticals reported a net loss of $111.3 million for Q4 2024, compared to a net loss of $36.8 million in Q4 2023, and a full-year net loss of $235.8 million for 2024, up from $151.1 million in 2023[9]. - Total revenue for the year ended December 31, 2024, was $6,853,000, compared to $6,853,000 for the year ended December 31, 2023, indicating no growth[16]. - The net loss for the year ended December 31, 2024, was $235,757,000, compared to a net loss of $151,085,000 for the year ended December 31, 2023, reflecting a 56.0% increase in losses[16]. - The loss from operations for the year ended December 31, 2024, was $201,055,000, compared to $171,283,000 in 2023, representing a 17.3% increase[16]. - Interest income for the year ended December 31, 2024, was $14,016,000, up from $10,476,000 in 2023, indicating a 33.0% increase[16]. Research and Development - Research and Development (R&D) expenses for Q4 2024 were $60.9 million, an increase from $29.7 million in Q4 2023, and full-year R&D expenses totaled $150.2 million for 2024, compared to $124.4 million in 2023[9]. - A one-time charge of $31.5 million related to the discontinuation of the SerpinPC program was included in R&D expenses for 2024[9]. - Research and development expenses increased to $150,244,000 for the year ended December 31, 2024, up from $124,405,000 in 2023, representing a 20.7% increase[16]. - The Phase 2a CRYSTAL-1 study of ORX750 is ongoing, with data expected across all three indications (NT1, NT2, and IH) in 2025[9]. - ORX750 demonstrated significant improvement in wakefulness in a Phase 1 study, achieving mean sleep latencies of 38 minutes at the 5.0 mg dose compared to 15 minutes for placebo[6]. - The company plans to present data from the Phase 1 study of ORX750 at the American Academy of Neurology Annual Meeting on April 5, 2025[6]. - ORX142 is advancing through IND-enabling studies, with clinical data expected in 2025, while ORX489 is also in IND-enabling studies[9]. - The company is focused on developing a pipeline of OX2R agonists aimed at treating excessive daytime sleepiness and related symptoms in various disorders[3]. Financial Position - Cash, cash equivalents, and short-term investments amounted to $482.2 million as of December 31, 2024, expected to fund operations into mid-2027[9]. - Total assets increased to $576,798,000 as of December 31, 2024, from $360,246,000 as of December 31, 2023, marking a 60.2% growth[18]. - Cash and cash equivalents rose significantly to $383,221,000 as of December 31, 2024, compared to $128,030,000 in 2023, indicating a 199.4% increase[18]. - Total liabilities increased to $175,253,000 as of December 31, 2024, from $124,002,000 in 2023, which is a 41.2% rise[18]. - Total shareholders' equity increased to $401,545,000 as of December 31, 2024, from $236,244,000 in 2023, reflecting a 69.9% growth[18]. - The weighted average ordinary shares outstanding increased to 132,050,271 for the quarter ended December 31, 2024, compared to 97,923,585 for the same quarter in 2023, reflecting a 34.8% increase[16]. General and Administrative Expenses - General and administrative expenses for Q4 2024 were $13.7 million, compared to $12.3 million in Q4 2023, and full-year expenses were $50.8 million for 2024, down from $53.7 million in 2023[9].