Centessa Pharmaceuticals (NasdaqGS:CNTA) 2025 Conference November 18, 2025 09:00 AM ET Company ParticipantsMario Alberto Accardi - President of Orexin ClassConference Call ParticipantsClara Dong - Biotech AnalystClara DongThanks for joining Jefferies Global Healthcare Conference in London. My name is Clara Dong, one of the biotech analysts at Jefferies here. Sitting next to me, we have Dr. Mario Alberto Accardi, the President of Orexin Class from Centessa Pharmaceuticals. Welcome.Mario Alberto AccardiThank ...

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]

Group 1 - Centessa Pharmaceuticals (NASDAQ:CNTA) is recognized as a promising stock with significant upside potential, with a Buy rating and a price target of $39.00 set by LifeSci Capital analyst Francois Brisebois [1][3] - In Q2 2025, Centessa reported cash and investments totaling $404.1 million, which is expected to sustain operations until mid-2027. R&D expenses rose to $42.7 million from $32.8 million in Q2 2024, resulting in a net loss of $50.3 million compared to a net loss of $43.8 million in the previous year [2] - The company is advancing its orexin receptor 2 (OX2R) agonist pipeline, with its lead candidate ORX750 in a Phase 2a study for narcolepsy and idiopathic hypersomnia, and data from this study is expected within the year [3] Group 2 - Centessa Pharmaceuticals is a clinical-stage pharmaceutical company focused on discovering, developing, and delivering medicines [4]

Summary of Centessa Pharmaceuticals FY Conference Call Company Overview - **Company**: Centessa Pharmaceuticals (NasdaqGS:CNTA) - **Focus**: Development of orexin agonists for treating narcolepsy and other sleep disorders Key Industry Insights - **Orexin Agonist Program**: Centessa is making significant progress in the orexin agonist space, which is seen as transformative for patients suffering from excessive daytime sleepiness and narcolepsy [4][8][9] - **Patient Population**: Approximately 80,000 patients have narcolepsy type 1 (NT1), with a larger number suffering from narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH). However, only a small subset of these patients are currently diagnosed and treated [8][9] Core Product Insights - **Lead Drug**: ORX-750, an orexin receptor 2 (OX2R) agonist, is designed to treat the underlying cause of narcolepsy by stimulating orexin signaling [16][19] - **Phase 1 Data**: At a 5 mg dose, ORX-750 maintained wakefulness for an average of 38 minutes across four time points during the night, indicating its potential efficacy [18] - **Phase 2a CRYSTAL-1 Study**: Ongoing studies for NT1, NT2, and IH with a flexible, real-time drug development approach to optimize dosing based on patient responses [19][20] Competitive Landscape - **Market Potential**: The market for NT1 alone is estimated at $6 to $7 billion, with NT2 and IH representing even larger populations, suggesting a total market potential exceeding $15 billion for rare hypersomnias [60][61] - **Differentiation**: ORX-750 is positioned as a best-in-class drug due to its unique pharmacokinetic (PK) profile, allowing for once-daily dosing and flexibility in administration [16][27] Safety and Efficacy Considerations - **Safety Profile**: Initial phase 1 data indicated a favorable safety profile with tolerability similar to placebo, which is crucial for patient acceptance [29][30] - **Potential Side Effects**: Concerns about liver toxicity and insomnia were raised, but the company aims to minimize adverse effects through careful drug design [23][24] Future Developments - **Upcoming Data**: Centessa plans to release data for NT1, NT2, and IH in 2025, along with data for ORX-142, another orexin agonist currently in clinical trials [22][49] - **ORX-142**: This compound is reported to be more potent than ORX-750, potentially allowing for lower dosing and broader therapeutic applications [49][53] Financial Position - **Cash Reserves**: Centessa reported $400 million in cash as of June 30, 2025, providing a runway into mid-2027 [59] Conclusion - Centessa Pharmaceuticals is positioned to redefine treatment paradigms in the sleep disorder space with its innovative orexin agonist programs, particularly ORX-750 and ORX-142, targeting significant unmet medical needs in narcolepsy and related conditions. The company is optimistic about its market potential and the transformative impact of its therapies on patient quality of life [60][61]