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].

Core Insights - Centessa Pharmaceuticals is advancing its pipeline of OX2R agonists, particularly ORX750, which shows promise in treating excessive daytime sleepiness (EDS) and related disorders [2][4][11] - The company reported significant financial results for Q4 and full-year 2024, including a net loss of $111.3 million for Q4 and $235.8 million for the full year, reflecting increased R&D expenses [11][12] Recent Highlights - The Phase 2a CRYSTAL-1 study for ORX750 is on track, with data expected in 2025 for narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) [4][11] - ORX142 and ORX489 are also in IND-enabling studies, with clinical data planned for 2025 [4][11] Financial Results - Cash, cash equivalents, and short-term investments totaled $482.2 million as of December 31, 2024, expected to fund operations into mid-2027 [11] - R&D expenses increased to $60.9 million in Q4 2024 from $29.7 million in Q4 2023, and full-year R&D expenses rose to $150.2 million from $124.4 million [11][12] - General and administrative expenses were $13.7 million for Q4 2024, compared to $12.3 million in Q4 2023 [11][12] - The net loss for Q4 2024 was $111.3 million, up from $36.8 million in Q4 2023, and the full-year net loss increased from $151.1 million in 2023 to $235.8 million in 2024 [11][12] Pipeline and Anticipated Upcoming Milestones - ORX750 is expected to provide data across all three indications in 2025, with a poster presentation scheduled for the AAN Annual Meeting on April 5, 2025 [5][11] - ORX142 and ORX489 are advancing through IND-enabling studies, with clinical data anticipated in 2025 [4][11]

Group 1 - Centessa Pharmaceuticals announced the presentation of Phase 1 clinical trial data for ORX750, a novel OX2R agonist aimed at treating narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) at the AAN 2025 Annual Meeting [1] - The ongoing Phase 2a clinical trial (CRYSTAL-1) is evaluating ORX750 in participants with NT1, NT2, and IH [1] - The poster presentation will take place on April 5, 2025, with details including the title, abstract number, and presenter provided [2] Group 2 - Centessa Pharmaceuticals is focused on developing best-in-class OX2R agonists for sleep-wake disorders and anticipates potential applications in treating cognitive deficits and excessive daytime sleepiness [3] - The company is also advancing an earlier stage pipeline in immuno-oncology utilizing its proprietary LockBody® technology platform [3]

Summary of Centessa Pharmaceuticals (CNTA) Conference Call - February 06, 2025 Company Overview - **Company**: Centessa Pharmaceuticals (CNTA) - **Key Participants**: Debjit Chattopadhyay (Managing Director), Mario Accardi (President of the Orexin Program) Core Industry and Company Insights - **Industry**: Pharmaceuticals, specifically focusing on treatments for narcolepsy and excessive daytime sleepiness - **Key Product**: ORX750, an orexin agonist, which has shown promising results in clinical trials Key Points and Arguments 1. **Transformative Year**: 2024 was described as a transformative year for Centessa, with a significant focus on the Orexin program and the development of ORX750 [2][3] 2. **Clinical Trials**: ORX750 has successfully completed a Phase 1 study, demonstrating a best-in-class profile with a mean wakefulness period (MWP) of 38 minutes, significantly outperforming the placebo [3][4] 3. **Phase 2 Studies**: Initiated Phase 2 studies for narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) in 2024, with data expected in 2025 [4][41] 4. **Safety Profile**: The safety and tolerability profile of ORX750 is reported to be significantly differentiated from other similar drugs, with no relevant pharmacology across other GPCRs [6][7][9] 5. **Dosing Strategy**: The design of ORX750 allows for once-daily dosing, which is expected to maintain wakefulness throughout the day while allowing patients to return to sleep at night [12][13] 6. **Study Design**: The Phase 2 study design is unique, allowing for dose selection based on real-time data from unblinded cohorts, which is different from conventional studies [14][15] 7. **Market Potential**: The potential market for NT2 and IH is estimated to be over $7.5 billion, with additional opportunities in other conditions associated with excessive daytime sleepiness, such as Parkinson's disease and major depressive disorder [32][33] 8. **Future Plans**: The company aims to be first in class for NT2 and IH, with plans to progress each indication independently based on enrollment rates [41][42] Additional Important Insights 1. **Leadership Changes**: The hiring of Steve Caines as Chief Medical Officer is expected to enhance the company's capabilities in the CNS space [5] 2. **Regulatory Strategy**: The company plans to have data ready for an end-of-Phase 2 meeting, which will facilitate the transition to registration studies [41] 3. **Flexibility in Development**: Centessa retains flexibility in its clinical development strategy, allowing for adjustments based on cohort performance and enrollment rates [26][27] 4. **Potential for Partnerships**: While the company has not ruled out partnerships for larger indications, it is confident in its ability to build a successful business model independently [39] This summary encapsulates the key discussions and insights from the conference call, highlighting Centessa Pharmaceuticals' strategic direction, clinical advancements, and market opportunities in the pharmaceutical industry.

Company Overview - Centessa Pharmaceuticals plc is a clinical-stage pharmaceutical company focused on discovering and developing transformational medicines for patients [2] - The company is developing potential best-in-class orexin receptor 2 (OX2R) agonists for the treatment of sleep-wake disorders, including narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH), and excessive daytime sleepiness (EDS) [2] - The lead OX2R agonist, ORX750, is currently in Phase 2 clinical trials for NT1, NT2, and IH [2] Recent Developments - The appointment of Stephen Kanes MD PhD as Chief Medical Officer (CMO) has been announced, bringing over 30 years of experience in neuroscience, clinical psychiatry, and drug development [1] - Dr. Kanes previously served as CMO at Sage Therapeutics, where he led the development of ZULRESSO® (brexanolone), the first treatment approved for Postpartum Depression [1] - The company anticipates a robust series of clinical milestones for its OX2R agonists throughout the year [1] Therapeutic Focus - Centessa's OX2R agonists aim to address unmet patient needs across multiple therapeutic areas, including sleep-wake, neurological, neurodegenerative, and psychiatric disorders [1] - The company also aims to explore the utility of OX2R agonists in treating impaired attention, cognitive deficits, and fatigue [2] - The proprietary LockBody technology platform is designed to redefine immuno-oncology treatment for cancer patients by selectively targeting the tumor micro-environment while minimizing systemic toxicity [2]

Pipeline Development - Centessa Pharmaceuticals is developing a pipeline of high conviction programs targeting unmet medical needs in multi-billion-dollar markets[114]. - The most advanced program is ORX750, an OX2R agonist for treating sleep-wake disorders, with a favorable safety and tolerability profile observed in Phase 1 studies[115][116]. - A Phase 2a clinical study of ORX750 has been initiated to evaluate its safety, tolerability, and pharmacokinetics in patients with narcolepsy and idiopathic hypersomnia, with initial dosing set at 1.0 mg for NT1 and 2.0 mg for NT2 and IH[127]. - ORX142, a second OX2R agonist candidate, is being advanced for neurological and psychiatric disorders, with preclinical data showing efficacy in promoting wakefulness[128]. - ORX489, the third OX2R agonist candidate, is entering IND-enabling activities for additional neurological and psychiatric disorders[129]. - The LockBody technology platform is being utilized to develop LB101, a bi-specific monoclonal antibody for treating solid tumors, with a Phase 1/2a study initiated in March 2023[130]. Clinical Study Updates - Interim data from the Phase 1 study showed significant increases in wakefulness at doses of 1.0 mg and 2.5 mg compared to placebo, with mean sleep latencies of 18 minutes and 32 minutes respectively[117][120]. - The Phase 1 study has completed three single-ascending dose cohorts and demonstrated a clear dose-dependent response in wakefulness[119][120]. - The Phase 1 study of ORX750 is ongoing, with dose escalation continuing in various cohorts, and a presentation of data is planned for a medical conference in the second quarter of 2025[126]. Financial Performance - Research and development expenses for Q3 2024 were $33.9 million, an increase from $28.2 million in Q3 2023, primarily due to higher costs associated with the OX2R agonist program[150]. - General and administrative expenses for Q3 2024 were $12.5 million, compared to $12.0 million in Q3 2023, with personnel expenses increasing by $0.8 million[151]. - The net loss for Q3 2024 was $42.6 million, compared to a net loss of $38.6 million in Q3 2023[148]. - Interest income for Q3 2024 was $3.3 million, up from $2.9 million in Q3 2023, while interest expense was $2.6 million, slightly higher than $2.5 million in the same period[152]. - Other income for Q3 2024 was a net gain of $3.7 million, compared to a net expense of $1.7 million in Q3 2023[153]. - The company recorded an income tax expense of $0.6 million in Q3 2024, contrasting with an income tax benefit of $2.8 million in Q3 2023[154]. - Research and development expenses for the nine months ended September 30, 2024, were $89.4 million, down from $94.7 million for the same period in 2023[155]. - General and administrative expenses for the nine months ended September 30, 2024, were $37.1 million, down from $41.4 million in the prior year, primarily due to the absence of ERP system implementation costs[157]. - Interest income increased to $9.2 million for the nine months ended September 30, 2024, up $1.6 million from the same period in 2023, due to interest earned from cash and cash equivalents[158]. - Interest expense rose to $7.6 million in the first nine months of 2024, an increase of $0.3 million compared to the same period in 2023, attributed to a higher average interest rate on the Note Purchase Agreement[159]. - Other income for the nine months ended September 30, 2024, was a net gain of $2.3 million, compared to a net expense of $4.6 million in the same period of 2023, mainly due to foreign currency transaction gains[160]. Cash and Financing - As of September 30, 2024, the company had cash, cash equivalents, and short-term investments totaling $518.4 million, expected to fund operations into mid-2027[134]. - The company completed a public offering of 17,542,372 ADSs at an offering price of $14.75 per ADS, resulting in net proceeds of approximately $242.7 million[166]. - Net cash used in operating activities for the nine months ended September 30, 2024, was $99.3 million, an improvement from $129.3 million in the same period of 2023[168]. - Net cash provided by financing activities for the nine months ended September 30, 2024, was $361.8 million, significantly higher than $14.8 million in the prior year, primarily due to proceeds from share offerings[173]. - The company sold 1,250,000 ordinary shares under the ATM Program in the nine months ended September 30, 2024, generating net proceeds of $9.7 million[165]. Strategic Decisions - The company announced the discontinuation of the global clinical development of SerpinPC, reallocating approximately $200 million in net savings towards the OX2R agonist program[131]. - The company plans to explore potential strategic alternatives for SerpinPC following its discontinuation[131]. - The company expects aggregate expenses in 2024 to be similar to 2023, reflecting higher costs related to the SerpinPC registration program and increased spending on the OX2R agonist portfolio[174]. - Future expenses are anticipated to increase significantly as the company seeks to discover and develop current and future clinical and preclinical product candidates[174]. - The company will need to rely on additional financing to achieve business objectives, as commercial revenues from product candidates are not expected for the next couple of years[176]. Tax and Obligations - The company has provided a valuation allowance for the full amount of the net deferred tax assets in the U.K. due to a history of cumulative net losses[190]. - The company entered into a Note Purchase Agreement in October 2021, obligating it to pay a milestone payment equal to 30% of the aggregate principal amount upon regulatory approval of any drug candidate[183]. - The fair value of the Note Purchase Agreement is based on the present value of estimated future payments, including interest and principal[185]. - The company measures share-based awards at their grant-date fair value and records compensation expense over the vesting period[186]. - The company is classified as an emerging growth company and a smaller reporting company, allowing it to delay the adoption of new accounting standards[192][193]. - As of September 30, 2024, the company had no material contractual obligations and other commitments associated with enforceable contracts[191].