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]

Centessa Pharmaceuticals (CNTA) Conference February 06, 2025 01:00 PM ET Company Participants Debjit Chattopadhyay - Managing DirectorMario Accardi - President of the Orexin Program Debjit Chattopadhyay Good afternoon, and thank you for joining Guggenheim's second, Smithcap conference. I am Devchit, and joining me from Syntesa is Mario Carty, the president of the Orexin program. Did I get that right? Mario Accardi You did. Yes, Doug. Hi. Great to be here with you. Debjit Chattopadhyay Well, it's been a very ...

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].

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]