Summary of Centessa Pharmaceuticals FY Conference Call Company Overview - Centessa Pharmaceuticals is a clinical-stage biotech company focused on orexin biology and orexin agonism, particularly in the treatment of sleep disorders such as narcolepsy and idiopathic hypersomnia [2][3] Key Developments - The company recently updated its Phase 2 study results involving approximately 50-55 patients across Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2), and Idiopathic Hypersomnia (IH) [2][3] - Centessa is the first company to present a robust dataset demonstrating statistically significant efficacy across all three indications [2][3] Pipeline and Future Studies - The lead asset, ORX750, is currently in Phase 2, with additional molecules ORX142 and ORX489 entering Phase 1 studies in Q1 2026 [3][4] - The company aims to expand beyond rare hypersomnias into neurodegenerative and psychiatric conditions [4] Efficacy Data - In NT1, a second dose of 1.5 mg showed a greater than 20-minute change from baseline in the Maintenance of Wakefulness Test (MWT), with half of the patients showing over 30 minutes improvement [6][7] - For NT2, a 4 mg dose resulted in a greater than 10-minute change from baseline, with the Epworth Sleepiness Scale (ESS) improving from 15-16 to 8 [7][8] - In IH, the initial 2 mg dose demonstrated clinically significant improvements in MWT and other efficacy measures [8] Safety and Tolerability - The drug has shown a favorable safety profile, with no significant adverse events reported, and only one dropout due to a pre-existing condition [31][32] Registration Program - The registration program is set to commence in Q1 2026, with flexibility to initiate across all three indications or staggered based on data from the next 50 patients [27][28] Competitive Landscape - The company believes it has a best-in-class profile based on the totality of evidence, including MWT, ESS, and tolerability metrics [34] - The orexin agonist class is viewed as having significant potential, akin to GLP-1 in the field of neurosciences [37] Intellectual Property - Centessa has developed a strong IP portfolio, with protections extending past 2040, based on unique structural biology technology [40] Conclusion - Centessa Pharmaceuticals is positioned to make significant advancements in the treatment of sleep disorders and potentially other neuropsychiatric conditions, with promising data from its lead asset and a robust pipeline [42]

Core Insights - 5AM Venture Management reduced its stake in Centessa Pharmaceuticals by 150,000 shares, now holding 680,945 shares, but the overall position value increased due to an 80% rise in stock price last quarter [2][6] - Centessa's stock price reached $29.03, reflecting a 65% increase over the past year, significantly outperforming the S&P 500's 14% gain in the same period [3][4] - The company has a market capitalization of $4.2 billion and reported a revenue of $15 million with a net loss of $242.7 million for the trailing twelve months [4] Company Overview - Centessa Pharmaceuticals is a UK-based biotechnology company focused on developing clinical-stage biopharmaceutical products for rare and serious diseases, including Lixivaptan for autosomal dominant polycystic kidney disease and SerpinPC for hemophilia [5] - The company is advancing a pipeline that targets conditions such as hemophilia, pulmonary arterial hypertension, and autoimmune diseases, serving a global patient base [5] Financial Performance - In the third quarter, Centessa reported a net loss of $54.9 million and ended the quarter with $349 million in cash and equivalents, sufficient to fund operations into mid-2027 [8] - The company announced a $250 million public offering at $21.50 per American Depositary Share (ADS) to strengthen its balance sheet [8] Market Position and Future Outlook - The decision by 5AM Venture Management to trim its position rather than exit indicates ongoing confidence in Centessa's potential, particularly in light of its promising clinical data and pipeline [6][9] - Centessa's orexin agonist platform is a key driver, with Phase 2a data showing significant improvements in wakefulness measures, and plans for a registrational program set to begin in Q1 2026 [8]

Summary of Centessa Pharmaceuticals Conference Call Company Overview - Centessa Pharmaceuticals is a clinical-stage biotech company focused on developing orexin agonists for treating excessive daytime sleepiness disorders, particularly narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) [3][4][5] Core Insights and Arguments - **Orexin Agonists**: The company is developing a novel class of drugs targeting the orexin system, which is crucial for regulating sleep and wakefulness. The loss of orexin leads to debilitating symptoms in narcolepsy patients [3][4] - **Clinical Data**: Recent phase two study results showed significant efficacy of their lead drug, ORX750, across all three indications. The data indicated a potential best-in-class profile, particularly in NT1 and NT2 [4][6][10] - **Efficacy Metrics**: In NT1, 50% of patients achieved a mean wakefulness time (MWT) of over 30 minutes at a low dose of 1.5 mg. The Epworth Sleepiness Scale (ESS) showed a reduction of 13 points, indicating substantial improvement in patient-reported outcomes [12][13] - **Safety Profile**: The drug demonstrated a clean safety profile with no serious adverse events reported. Visual disturbances were mild and transient, not affecting the therapeutic index [20][30] - **Pharmacokinetics**: ORX750 has a flat pharmacokinetic (PK) curve, allowing for once-daily (QD) dosing, which is advantageous for patient compliance and efficacy [21][22] Market Opportunity - The combined market for NT1, NT2, and IH is estimated at $18 billion, with a prevalence of approximately 620,000 patients. There is significant unmet clinical need, as current treatments do not adequately address the symptoms for many patients [34][38] Future Plans - Centessa plans to continue its phase two studies and initiate a registration program in Q1 2026. The company has raised $270 million to support these efforts [5][33] - The company is also developing additional candidates, ORX142 and ORX489, which are expected to enter patient studies in Q1 2026 [34][37] Additional Considerations - **Dosing Flexibility**: The potential for split dosing is being evaluated to enhance symptom control for patients with varying schedules [23][24] - **Competitive Landscape**: Centessa aims to differentiate itself from competitors by focusing on the unique efficacy and tolerability of its orexin agonists [27][28] - **Long-term Vision**: The company sees orexin agonists as having broader applications beyond narcolepsy, potentially impacting various neurodegenerative disorders and cognitive functions [35] Financial Position - Centessa's balance sheet shows a proforma cash position of $620 million, providing a solid runway for ongoing and future clinical programs [39]

Core Viewpoint - Centessa Pharmaceuticals plc (NASDAQ:CNTA) has achieved a new all-time high due to a planned fundraising program that could generate up to $287.5 million in fresh funds [1][3]. Fundraising Details - Centessa plans to issue over 11.6 million new American depositary shares (ADS) at a price of $21.50 each, with each ADS representing one ordinary share [2]. - The company has granted underwriters a 30-day option to purchase an additional 1,744,186 ADS at the same price [3]. - The fundraising offer is expected to close on November 14, subject to closing conditions [3]. Financial Performance - In the third quarter, Centessa reported a widened net loss of $54.89 million, a 29% increase from $42.57 million in the same period last year [4]. - The operating loss increased by 15.9% to $53.79 million from $46.4 million year-on-year, primarily due to higher operating expenses related to research and development initiatives [4].

Summary of Centessa Pharmaceuticals FY Conference Call Company Overview - **Company**: Centessa Pharmaceuticals (NasdaqGS:CNTA) - **Event**: FY Conference on November 12, 2025 - **Presenters**: Saurabh Saha (CEO), Mario Accardi (President of the Orexin Program) Key Points Industry and Product Focus - Centessa Pharmaceuticals is not limited to narcolepsy but is exploring broader applications of its drug ORX-750, which targets orexin signaling in various neurological conditions [5][6] - The company has reported positive clinical data for ORX-750 across three indications: Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2), and Idiopathic Hypersomnia (IH) [5][6] Clinical Data and Efficacy - ORX-750 has shown clinically meaningful effectiveness in NT1 and NT2, with significant changes in the Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) [11][12] - In NT2, a greater than 10-point change from baseline in MWT and a drop in ESS from 16 to 8 were reported, indicating strong efficacy [11][12] - In NT1, a greater than 20-point change from baseline in MWT was observed, with half of the patients at the 1.5 mg dose showing over 30 on mean MWT [12] Drug Development Strategy - Centessa employs a real-time drug development approach, allowing for dose adjustments based on ongoing data analysis [7][8] - The company emphasizes the importance of dose-responsive data and has achieved linear exposure with dose [10] Tolerability and Safety - ORX-750 is reported to be well-tolerated, with mild adverse events (AEs) such as polyuria and insomnia, which are not dose-limiting [15][16] - The drug has shown a favorable pharmacokinetic (PK) profile, allowing for higher dose escalation without significant safety concerns [15][16] Regulatory and Market Position - Centessa plans to initiate its registration program in early 2026, with ongoing discussions with the FDA [49] - The company believes that orexin agonists will serve as monotherapy across NT1, NT2, and IH, addressing a significant unmet clinical need [43][44] Competitive Landscape - Centessa positions ORX-750 as potentially best-in-class based on its clinical data compared to competitors [11][12] - The company aims to differentiate itself by offering a drug with a robust duration of action, reducing the need for polypharmacy in patients [44][45] Future Directions - The company is exploring split dosing to provide flexibility for patients, allowing for better symptom control throughout the day [21][23] - Ongoing studies will refine the understanding of normative wakefulness thresholds and the drug's efficacy across different patient populations [27][28] Market Opportunity - The total addressable market for narcolepsy treatments is larger than current revenue figures suggest, as many patients are on generic medications that do not adequately control symptoms [48] Additional Insights - The company is focused on ensuring rigorous patient selection criteria to avoid confounding data in clinical trials [36][37] - Centessa is committed to addressing the challenges of disturbed nighttime sleep associated with narcolepsy, which is a significant concern for patients [43][44]

Group 1 - Centessa Pharmaceuticals plc has announced the pricing of an underwritten public offering of 11,627,907 American Depositary Shares (ADSs) at a price of $21.50 per ADS, with expected gross proceeds of approximately $250 million before deductions [1] - The offering is expected to close on or about November 14, 2025, subject to customary closing conditions, and includes a 30-day option for underwriters to purchase an additional 1,744,186 ADSs [1] - The ADSs are being offered under a registration statement filed with the SEC, which became effective upon filing [3] Group 2 - Jefferies, Leerink Partners, Evercore ISI, and Guggenheim Securities are acting as joint book-running managers for the offering, while Oppenheimer & Co., Truist Securities, and LifeSci Capital are co-lead managers [2] - The final prospectus supplement and accompanying prospectus related to the offering will be filed with the SEC and will be available on the SEC's website [3] Group 3 - Centessa Pharmaceuticals is a clinical-stage pharmaceutical company focused on discovering and developing transformative medicines, particularly in the area of orexin receptor 2 (OX2R) agonist program for treating excessive daytime sleepiness and other neurological disorders [5]

Core Viewpoint - Centessa Pharmaceuticals plc has initiated an underwritten public offering of American Depositary Shares (ADSs), with all shares being offered by the company, and plans to grant underwriters a 30-day option to purchase an additional 15% of the ADSs offered [1][2]. Company Overview - Centessa Pharmaceuticals is a clinical-stage pharmaceutical company focused on discovering, developing, and delivering transformative medicines for patients, particularly through its orexin receptor 2 (OX2R) agonist program aimed at treating excessive daytime sleepiness, cognitive deficits, and other neurological disorders [5]. Offering Details - The ADSs are being offered under a registration statement on Form S-3 filed with the SEC on September 11, 2024, which became effective upon filing [3]. - A preliminary prospectus supplement and accompanying prospectus will be filed with the SEC and will be accessible on the SEC's website [3]. Underwriters - Jefferies, Leerink Partners, Evercore ISI, and Guggenheim Securities are serving as joint book-running managers for the offering, while Oppenheimer & Co., Truist Securities, and LifeSci Capital are acting as co-lead managers [2]. Contact Information - For inquiries, the company has provided contact details for Kristen K. Sheppard, SVP of Investor Relations [7].

Financial Position - As of September 30, 2025, the company had cash, cash equivalents, and investments totaling $349.0 million, expected to fund operations into mid-2027[120] - As of September 30, 2025, the company had cash, cash equivalents, and investments totaling $349.0 million, with $50.8 million in cash and cash equivalents, $195.4 million in short-term investments, and $102.8 million in long-term investments[146] - The company raised $8.1 million from financing activities during the nine months ended September 30, 2025, mainly from the ATM program and employee stock option exercises[157] - The company has access to up to $200.0 million in term loans, with $110.0 million already received and additional tranches available upon achieving specific milestones[147][149] - The term loans are set to mature on December 1, 2029, with an option to extend to December 1, 2030, depending on certain conditions[150] Research and Development - The company is developing ORX750, an OX2R agonist, currently in Phase 2a clinical trials, with 55 participants completing dosing as of September 23, 2025[109] - ORX750 demonstrated statistically significant improvements in mean sleep latency on the Maintenance of Wakefulness Test (MWT) with a p-value of 0.0213 compared to placebo[111] - ORX142, another OX2R agonist, is in Phase 1 clinical trials, with 89 healthy adult participants dosed as of October 3, 2025, showing rapid onset of action and well-tolerated at all doses[117] - The Phase 2a study of ORX750 is expected to enable dose selection for a registrational program planned for the first quarter of 2026[112] - The company is advancing ORX489, its most potent OX2R agonist, into IND-enabling studies with clinical studies planned for the first quarter of 2026[118] - Research and development expenses are expected to increase significantly due to costs associated with clinical trials and regulatory filings for current and future product candidates[122] Financial Performance - The company recorded a net loss of $54.9 million for the three months ended September 30, 2025, compared to a net loss of $42.6 million for the same period in 2024, reflecting a 28.8% increase in losses[133] - For the nine months ended September 30, 2025, research and development expenses totaled $117.7 million, up 31.7% from $89.4 million for the same period in 2024[141] - Research and development expenses for the three months ended September 30, 2025, were $41.6 million, an increase of 22.5% from $33.9 million for the same period in 2024[134] - The OX2R agonist program accounted for $35.6 million in research and development expenses for the three months ended September 30, 2025, compared to $11.7 million in the same period of 2024[134] - The company recognized $15.0 million in license and other revenue during the nine months ended September 30, 2025, related to an upfront payment from Genmab A/S[140] - Interest and investment income for the nine months ended September 30, 2025, was $16.0 million, an increase of 75.2% from $9.2 million for the same period in 2024[143] - General and administrative expenses for the nine months ended September 30, 2025, were $36.5 million, a slight decrease from $37.1 million for the same period in 2024[142] - Interest expense for the nine months ended September 30, 2025, was $8.7 million, up 13.1% from $7.6 million for the same period in 2024[144] - Other non-operating income for the nine months ended September 30, 2025, was $2.8 million, compared to $2.3 million for the same period in 2024, primarily due to foreign currency transaction gains[145] Operational Challenges - The company has incurred recurring losses and negative cash flows since inception, primarily funded through equity securities and debt financing[120] - The company expects to continue incurring significant development costs as it progresses through clinical trials and regulatory approvals[127] - During the nine months ended September 30, 2025, the company used $138.0 million in operating activities, reflecting a net loss of $131.4 million, adjusted by non-cash charges of $22.3 million[154] - The company incurred net cash used in investing activities of $200.4 million during the nine months ended September 30, 2025, primarily due to investments in marketable securities[156] - The company anticipates significant increases in expenses as it continues the development of product candidates and seeks marketing approvals, necessitating substantial additional funding[158] Licensing and Partnerships - The company has out-licensed its LockBody technology platform to Genmab for up to three targets, indicating potential revenue generation opportunities[121] Company Classification - The company is classified as an emerging growth company and a smaller reporting company, allowing it to benefit from reduced reporting requirements[164][166]

Financial Performance - Cash, cash equivalents, and investments totaled $349.0 million as of September 30, 2025, expected to fund operations into mid-2027[15] - Net loss for Q3 2025 was $54.9 million, compared to a net loss of $42.6 million in Q3 2024, indicating a 29% increase in losses year-over-year[15] - For the three months ended September 30, 2025, Centessa Pharmaceuticals reported a net loss of $54,891,000, compared to a net loss of $42,566,000 for the same period in 2024, representing a 29% increase in losses year-over-year[24] - Total assets decreased to $448,300,000 as of September 30, 2025, down from $576,798,000 at the end of 2024, reflecting a 22% decline[26] - Cash and cash equivalents significantly dropped to $50,811,000 from $383,221,000, marking an 87% decrease[26] - The company reported total liabilities of $146,726,000 as of September 30, 2025, down from $175,253,000 at the end of 2024, a reduction of 16%[26] - Interest and investment income for the nine months ended September 30, 2025, was $16,035,000, compared to $9,171,000 in the same period of 2024, showing a 75% increase[24] - The weighted average ordinary shares outstanding increased to 134,163,492 for the three months ended September 30, 2025, compared to 116,253,902 for the same period in 2024, a rise of 15%[24] Research and Development - Research & Development (R&D) expenses were $41.6 million for Q3 2025, up from $33.9 million in Q3 2024, representing a 22% increase[15] - Research and development expenses for the nine months ended September 30, 2025, were $117,747,000, up from $89,370,000 in the same period of 2024, indicating a 32% increase[24] - ORX750 achieved a >20 minute change from baseline in mean sleep latency on the Maintenance of Wakefulness Test (MWT) at Week 2 in the 1.5 mg cohort (p-value = 0.0026)[6] - In the 1.5 mg cohort for NT2, ORX750 showed a mean Epworth Sleepiness Scale (ESS) total score of 5.1 compared to 18.7 with placebo at Week 2 (p-value = 0.0001)[6] - ORX750 demonstrated an 87% relative reduction in Weekly Cataplexy Rate (WCR) in the 1.5 mg cohort compared to placebo (p-value = 0.0025)[6] - ORX142 Phase 1 study included 89 healthy volunteers, showing statistically significant and dose-dependent improvements in mean sleep latency on the MWT[9] - The registrational program for ORX750 is expected to be initiated in Q1 2026[10] - ORX489 is advancing through IND-enabling studies, with clinical studies expected to begin in Q1 2026, subject to IND clearance[15] - The company has ongoing clinical trials for product candidates ORX750, ORX142, and ORX489, with expectations for future results being subject to various risks and uncertainties[20] Funding and Risks - Centessa Pharmaceuticals has a financing facility with Oxford Finance to support its planned clinical trials and other expenses, indicating a focus on securing adequate funding[20] - The company is facing various risks including regulatory, economic, and competitive challenges that could impact its clinical development and commercialization efforts[20] Administrative Expenses - General & Administrative (G&A) expenses were $12.2 million for Q3 2025, slightly down from $12.5 million in Q3 2024[15]

Core Insights - Centessa Pharmaceuticals reported significant progress in its OX2R agonist program, particularly with ORX750, which shows potential as a best-in-class treatment for narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) [2][5][9] - The company plans to initiate a registrational program for ORX750 in Q1 2026, supported by promising Phase 2a data demonstrating statistically significant improvements in key efficacy measures [2][5][14] OX2R Agonist Program Updates - ORX750 achieved statistically significant, clinically meaningful, and dose-dependent results in the Maintenance of Wakefulness Test (MWT), Epworth Sleepiness Scale (ESS), and Weekly Cataplexy Rate (WCR) across initial cohorts [2][6][9] - The Phase 2a study included 55 participants, with ORX750 showing a favorable safety profile and transient mild to moderate treatment-emergent adverse events [4][9] - ORX142, another candidate in the program, demonstrated a highly differentiated profile in Phase 1 studies, with plans for patient studies to begin in Q1 2026 [2][10][14] Financial Performance - As of September 30, 2025, the company reported cash, cash equivalents, and investments totaling $349.0 million, expected to fund operations into mid-2027 [19] - Research and development expenses for Q3 2025 were $41.6 million, an increase from $33.9 million in Q3 2024, while general and administrative expenses were relatively stable at $12.2 million [19][23] - The net loss for Q3 2025 was $54.9 million, compared to a net loss of $42.6 million in the same period of the previous year [19][23]