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]

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].

Exhibit 99.1 Centessa Pharmaceuticals Reports Financial Results for the Third Quarter of 2024 and Provides Business Update • Announced additional interim data from ongoing Phase 1 clinical study of ORX750, a novel orexin receptor 2 (OX2R) agonist, in acutely sleep-deprived healthy volunteers that further support best-in-class potential of ORX750 in narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH); Presentation of Phase 1 data planned for medical congress in Q2 2025 • Initiat ...

Announced additional interim data from ongoing Phase 1 clinical study of ORX750, a novel orexin receptor 2 (OX2R) agonist, in acutely sleep-deprived healthy volunteers that further support best-in-class potential of ORX750 in narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH); Presentation of Phase 1 data planned for medical congress in Q2 2025Initiated Phase 2a clinical study of ORX750 in patients with NT1, NT2 and IH; Phase 2a data across all three indications expected in 20 ...

Centessa Pharmaceuticals Today | --- | --- | |--------------------------|-------| | | | | | | | CNTA | | | Centessa Pharmaceuticals | | | $15.79 | | | +0.12 (+0.77%) | | | 52-Week Range $5.15 | | | ▼ | | | $17.59 | | | Price Target $25.17 | | | Add to Watchlist | | Centessa Pharmaceuticals NASDAQ: CNTA is a biotechnology stock that has nearly doubled its value so far this year, and its run may not be over. Analysts at Morgan Stanley have just massively raised their price target for the company. The re-ratin ...

Core Insights - Centessa Pharmaceuticals has presented new preclinical data supporting ORX142 as a novel drug candidate for treating excessive daytime sleepiness (EDS) in specific neurological, neurodegenerative, and psychiatric disorders [1][3] - ORX142 is a potent orexin receptor 2 (OX2R) agonist, showing significant activity in promoting wakefulness at low doses in non-human primate models [2][4] Company Overview - Centessa Pharmaceuticals is a clinical-stage pharmaceutical company focused on discovering and developing transformational medicines for patients [7] - The company is advancing a pipeline of orexin receptor 2 (OX2R) agonists, including ORX750 and ORX142, targeting sleep-wake disorders [6][7] Preclinical Data Highlights - ORX142 demonstrated significant increases in wake times at a dose of 0.03 mg/kg, the lowest oral dose tested in non-human primate models [3][4] - The drug showed an EC50 of 0.069 nM for activating the human OX2R and was over 13,000-fold selective compared to the human orexin receptor 1 (hOX1R) [4] Presentation Details - The preclinical data were presented at the 27th Congress of the European Sleep Research Society in Seville, Spain, by Dr. Sarah Wurts Black [2] - The presentation highlighted ORX142's potential as a treatment for individuals with EDS in select neurodegenerative, neurological, and psychiatric disorders [3][4]