Financial Performance - Centessa Pharmaceuticals reported a net loss attributable to ordinary shareholders of $42.6 million for Q3 2024, compared to $38.6 million in Q3 2023, reflecting a year-over-year increase of approximately 5.2%[21] - Net loss for the nine months ended September 30, 2024, was $124.4 million, compared to $114.2 million for the same period in 2023, reflecting a year-over-year increase of approximately 8.5%[25] - The company reported a comprehensive loss of $42.1 million for Q3 2024, compared to a loss of $38.8 million in Q3 2023, reflecting an increase of about 5.9%[25] - Research and development expenses for Q3 2024 were $33.9 million, up from $28.2 million in Q3 2023, indicating a year-over-year increase of about 20.2%[20] - Research and development expenses for Q3 2024 were $33.9 million, up from $28.2 million in Q3 2023, while total operating loss increased to $46.4 million from $40.2 million year-over-year[25] - Interest income for Q3 2024 was $3.3 million, compared to $3.0 million in Q3 2023, indicating a year-over-year increase of approximately 13.1%[25] Cash and Liquidity - The company has $518.4 million in cash, cash equivalents, and short-term investments as of September 30, 2024, which is expected to fund operations into mid-2027[20] - Cash and cash equivalents as of September 30, 2024, were $395.0 million, significantly higher than $128.0 million at the end of 2023, indicating improved liquidity[26] - Total assets increased to $609.7 million as of September 30, 2024, compared to $360.2 million at the end of 2023, representing a growth of approximately 69.3%[26] - Total liabilities decreased to $110.6 million from $124.0 million at the end of 2023, showing a reduction of about 10.8%[26] Clinical Development - Interim data from the Phase 1 clinical study of ORX750 showed a mean sleep latency of 34 minutes at the 3.5 mg dose, with a placebo-adjusted mean sleep latency of 20 minutes, demonstrating significant efficacy[4] - Centessa initiated a Phase 2a clinical study of ORX750 in patients with narcolepsy type 1, type 2, and idiopathic hypersomnia, with data expected in 2025[2] - The Phase 2a study of ORX750 is designed to generate data across all three indications in 2025, potentially enabling it to be first-in-class in narcolepsy type 2 and idiopathic hypersomnia[11] - ORX142 is currently in IND-enabling studies, with clinical data expected in 2025, while ORX489 is entering IND-enabling studies as the next candidate in the OX2R agonist pipeline[3][18] - The company anticipates continued investment in its clinical pipeline, including ORX750, ORX142, and ORX489, with expectations for upcoming clinical trials[24] Strategic Decisions - The company announced a strategic decision to discontinue the clinical development of SerpinPC, reallocating approximately $200 million in net savings towards the expansion of the OX2R agonist franchise[12][14] - The company has identified potential net savings associated with the discontinuation of the SerpinPC program, which may impact future financials positively[24] Shareholder Impact - The weighted average ordinary shares outstanding increased to 116.3 million in Q3 2024 from 96.6 million in Q3 2023, indicating a dilution effect on per-share metrics[25]

Core Insights - Centessa Pharmaceuticals announced additional interim data from the ongoing Phase 1 clinical study of ORX750, indicating its best-in-class potential for treating narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) [1][2] - The company has initiated a Phase 2a clinical study of ORX750, with data expected in 2025, aiming for first-in-class potential in NT2 and IH [1][2] - Centessa has decided to discontinue the clinical development of SerpinPC, reallocating approximately $200 million in savings towards expanding its OX2R agonist franchise [1][11][12] OX2R Agonist Program - The Phase 1 clinical trial of ORX750 has shown significant increases in wakefulness in acutely sleep-deprived healthy volunteers, with a clear dose-dependent response [3][4] - The interim data revealed that treatment with ORX750 resulted in statistically significant increases in sleep latency compared to placebo, with the 3.5 mg dose achieving a mean sleep latency of 34 minutes [3][5] - A favorable safety profile was observed, with all treatment-emergent adverse events being mild and transient, and no significant changes in hepatic or renal parameters [5][6] Phase 2a Clinical Study - The Phase 2a study is designed as a randomized, double-blind, placebo-controlled, cross-over study to evaluate the safety, tolerability, and pharmacokinetics of ORX750 in patients with NT1, NT2, and IH [9][10] - Initial dosing for NT1 will be 1.0 mg, while NT2 and IH will start at 2.0 mg, with a total treatment duration of 6 weeks [9][10] - The study aims to generate data across all three indications in 2025, potentially enabling ORX750 to be first-in-class in NT2 and IH [10] Financial Overview - As of September 30, 2024, Centessa reported cash, cash equivalents, and short-term investments totaling $518.4 million, expected to fund operations into mid-2027 [15] - Research and development expenses for Q3 2024 were $33.9 million, an increase from $28.2 million in Q3 2023 [15] - The net loss attributable to ordinary shareholders for Q3 2024 was $42.6 million, compared to $38.6 million for the same period in 2023 [15]

Core Viewpoint - Centessa Pharmaceuticals has seen a significant increase in its stock value, with analysts raising price targets substantially, indicating strong potential for future growth [1][2]. Group 1: Stock Performance and Analyst Ratings - Centessa Pharmaceuticals (NASDAQ: CNTA) has nearly doubled its value this year, with a current price of $15.79, reflecting a 0.77% increase [1]. - Morgan Stanley raised its price target from $11 to $26, a 136% increase, suggesting a 66% upside from the current level [2]. - B. Riley has an even more optimistic price target of $33, indicating the stock could more than double from its current price [2]. Group 2: Drug Pipeline - Centessa has three main drugs in its pipeline: SerpinPC, ORX750, and LB101 [2][7]. - SerpinPC is in Phase 2 FDA trials for treating hemophilia A and B, showing solid safety and efficacy in previous trials [2]. - ORX750 targets excessive daytime sleepiness and narcolepsy, with positive interim Phase 1 results indicating it can restore wakefulness in sleep-deprived individuals [4][6]. - LB101 is aimed at treating solid tumors and is currently in Phase 1 FDA trials [7]. Group 3: Financial Position - Centessa currently has $295 million in cash and short-term investments, which can sustain operations for nearly two years based on a quarterly cash burn of around $40 million [8]. - The company recently priced a $225 million public offering, potentially extending its operational runway by another year [9]. Group 4: Market Sentiment and Analyst Commentary - Analysts have expressed strong optimism regarding Centessa's potential, with Morgan Stanley's analyst using strong language to describe the results of ORX750 as "de-risking" the mechanism of action for narcolepsy [10][12]. - Despite the positive sentiment, it is noted that only about 12% of drugs typically receive FDA approval after entering trials, indicating inherent risks in the biotech sector [13].

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]

Group 1 - Centessa Pharmaceuticals plc announced an upsized underwritten public offering of 15,254,237 American Depositary Shares (ADSs) at a price of $14.75 per ADS, expecting gross proceeds of approximately $225 million before expenses [1] - The offering is expected to close on or about September 16, 2024, subject to customary closing conditions, and underwriters have a 30-day option to purchase an additional 2,288,135 ADSs [1] - The ADSs are being offered under a registration statement filed with the SEC on September 11, 2024, which became effective upon filing [3] Group 2 - Goldman Sachs & Co. LLC, Leerink Partners, Evercore ISI, Guggenheim Securities, and BMO Capital Markets are acting as joint book-running managers for the offering [2] - Centessa Pharmaceuticals focuses on discovering and developing transformational medicines, with advanced programs in hemophilia, narcolepsy, and immuno-oncology [5]

Company Overview - Centessa Pharmaceuticals plc is a clinical-stage pharmaceutical company focused on discovering and developing transformational medicines for patients [5] - The company's advanced programs include treatments for hemophilia, narcolepsy, and immuno-oncology utilizing the LockBody® technology platform [5] Public Offering Details - Centessa Pharmaceuticals has announced a public offering of $150 million of American Depositary Shares (ADSs), each representing one ordinary share [1] - The company plans to grant underwriters a 30-day option to purchase up to an additional $22.5 million of ADSs [1] - The offering is subject to market conditions and there is no assurance regarding its completion or the actual size and terms [1] Underwriters - Goldman Sachs & Co. LLC, Leerink Partners, Evercore ISI, Guggenheim Securities, and BMO Capital Markets are acting as joint book-running managers for the offering [2]

2.5 mg dose restored normative wakefulness with mean sleep latency of 32 minutes as measured by the Maintenance of Wakefulness Test (MWT) Favorable safety and tolerability profile with no observations of frequently reported on-target adverse events (AEs) associated with other OX2R agonists, visual disturbances or hepatotoxicity as of the data cutoff date 1 PK profile supports once-daily dosing Company plans to rapidly initiate Phase 2 studies of ORX750 in patients with narcolepsy type 1 (NT1), narcolepsy ty ...

BOSTON and LONDON, Aug. 27, 2024 (GLOBE NEWSWIRE) -- Centessa Pharmaceuticals plc (Nasdaq: CNTA), today announced that preclinical data from a non-human primate (NHP) study of ORX142, a highly potent and selective orexin receptor 2 (OX2R) agonist being developed to address excessive daytime sleepiness (EDS) in select neurological, neurodegenerative, and psychiatric disorders, has been accepted for a latebreaking poster presentation at the 27th Congress of the European Sleep Research Society (Sleep Europe 20 ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (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, 2024 OR o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number 001-40445 CENTESSA PHARMACEUTICALS PLC (Exact name of registrant as specified in its charter) England and Wales 98- ...

Exhibit 99.1 Centessa Pharmaceuticals Reports Financial Results and Business Highlights for the Second Quarter of 2024 • Company advancing pipeline of potential best-in-class orexin receptor 2 (OX2R) agonists – Initiated Phase 1 clinical study with ORX750 being developed for sleep-wake disorders; Safety and ef icacy data in acutely sleep-deprived healthy volunteers assessed using Maintenance of Wakefulness Test (MWT) on track for 2H of 2024 – Nominated ORX142 as development candidate; Currently in IND enabl ...