Centessa Pharmaceuticals(CNTA) - 2023 Q4 - Annual Results

Business and Program Updates Centessa Pharmaceuticals advanced SerpinPC, ORX750, and LB101 programs, anticipating key milestones in 2024 - CEO emphasizes a laser focus on executing the PRESent registrational studies for SerpinPC and advancing the orexin receptor 2 (OX2R) agonist development program into the clinic for narcolepsy[2][3] - The company continues to evaluate its proprietary LockBody technology platform in a first-in-human clinical study of LB101 for solid tumors, designed to selectively drive CD47 into the tumor microenvironment[4] Recent Highlights Recent highlights include positive SerpinPC Phase 2a data, registrational study initiation, and promising ORX750 preclinical data - SerpinPC Phase 2a study showed a continued favorable safety and tolerability profile and sustained long-term efficacy, with a 96% reduction in median all-bleed annualized bleeding rate (ABR) over an additional 52 weeks of continuous treatment[4][17] - Dosing was initiated in July 2023 for the registrational PRESent-2 study (hemophilia B without inhibitors) and in October 2023 for the PRESent-3 study (hemophilia B with inhibitors) of SerpinPC[19] - Preclinical data for the investigational OX2R agonist, ORX750, announced in October 2023, supports its potential best-in-class profile for narcolepsy and other sleep-wake disorders[5][18] Anticipated Upcoming Program Milestones Key upcoming milestones include SerpinPC PRESent-2 interim analysis, ORX750 clinical proof-of-concept, and preclinical program updates - For the PRESent-2 study of SerpinPC, an interim analysis is planned in 2024 to confirm a dose and advance to Part 2, with Part 1 data expected to be shared in late 2024 or early 2025[2][6] - Upon Investigational New Drug (IND) clearance, ORX750 is planned to rapidly advance into clinical development with the goal of sharing clinical proof-of-concept data in sleep-deprived healthy volunteers in 2024[16][21] - Updates on preclinical programs, including follow-up orexin agonists and LB206 (PD-L1xCD3 LockBody), will be provided as they advance toward clinical studies[22] Fourth Quarter and Full-Year 2023 Financial Results Centessa reported reduced net loss and operating expenses for Q4 and FY2023, maintaining a strong cash position into 2026 - Cash, cash equivalents and short-term investments totaled $256.5 million as of December 31, 2023, which includes approximately $6.2 million in net proceeds from ATM sales in Q4 2023 and an additional $9.7 million in January 2024[23] - The company expects its current cash, cash equivalents and short-term investments will fund operations into 2026, without drawing on the remaining available tranches under the Oberland credit facility[23] Financial Highlights The company saw decreased net loss and operating expenses for Q4 and FY2023, while maintaining a robust cash runway Key Financial Highlights (Q4 and Full-Year 2023 vs. 2022) | Metric | Q4 2023 ($M) | Q4 2022 ($M) | FY 2023 ($M) | FY 2022 ($M) | | :----------------------------------- | :----------- | :----------- | :----------- | :----------- | | Research & Development Expenses | 29.7 | 27.8 | 124.4 | 155.1 | | General & Administrative Expenses | 12.3 | 13.8 | 53.7 | 55.2 | | Net Loss Attributable to Shareholders| 36.8 | 43.2 | 151.1 | 216.2 | Consolidated Statements of Operations and Comprehensive Loss Consolidated operations show a net loss of $36.8M for Q4 2023 and $151.1M for FY2023, improved by reduced operating expenses Consolidated Statements of Operations and Comprehensive Loss (Amounts in thousands) | Metric | Q4 2023 (Thousands) | Q4 2022 (Thousands) | FY 2023 (Thousands) | FY 2022 (Thousands) | | :------------------------------------------- | :------------------ | :------------------ | :------------------ | :------------------ | | License and other revenue | $6,853 | $— | $6,853 | $— | | Research and development | 29,716 | 27,835 | 124,405 | 155,083 | | General and administrative | 12,315 | 13,768 | 53,731 | 55,200 | | Loss from operations | (35,178) | (41,603) | (171,283) | (212,263) | | Net loss | (36,837) | (43,173) | (151,085) | (216,207) | | Net loss per ordinary share - basic and diluted | $(0.38) | $(0.45) | $(1.57) | $(2.31) | | Weighted average ordinary shares outstanding | 97,923,585 | 94,603,860 | 96,177,578 | 93,400,513 | Condensed Consolidated Balance Sheets Total assets decreased to $360.2M from $444.3M in 2022 due to reduced cash, while total liabilities increased to $124.0M Condensed Consolidated Balance Sheets (Amounts in thousands) | Metric | Dec 31, 2023 (Thousands) | Dec 31, 2022 (Thousands) | | :----------------------------------- | :----------------------- | :----------------------- | | Cash and cash equivalents | $128,030 | $393,644 | | Short-term investments | 128,519 | — | | Other assets | 103,697 | 50,663 | | Total assets | $360,246 | $444,307 | | Other liabilities | $48,302 | $38,338 | | Long term debt | 75,700 | 69,800 | | Total liabilities | $124,002 | $108,138 | | Total shareholders' equity | 236,244 | 336,169 | | Total liabilities and shareholders' equity | $360,246 | $444,307 | About Centessa Pharmaceuticals and Product Candidates Centessa is a clinical-stage company developing transformational medicines across hemophilia, narcolepsy, and immuno-oncology platforms - Centessa Pharmaceuticals plc is a clinical-stage pharmaceutical company that aims to discover and develop medicines transformational for patients[32] - The most advanced programs include a hemophilia program, an orexin agonist program for narcolepsy and other sleep-wake disorders, and an immuno-oncology program focused on the LockBody® technology platform[32] About Centessa Pharmaceuticals Centessa is a clinical-stage company dedicated to developing innovative medicines, focusing on hemophilia, narcolepsy, and immuno-oncology - The company operates with the conviction that each of its programs has the potential to change the current treatment paradigm and establish a new standard of care[32] About SerpinPC (Hemophilia Program) SerpinPC is an investigational, subcutaneously administered APC inhibitor for hemophilia, with Fast Track designation from the FDA - SerpinPC is an investigational subcutaneously administered novel inhibitor of APC being developed as a potential treatment for hemophilia, regardless of severity or inhibitor status[11][25] - The registrational program for SerpinPC in hemophilia B includes PRESent-2 (moderately severe to severe hemophilia B without inhibitors) and PRESent-3 (hemophilia B with inhibitors), along with an observational feeder study PRESent-5[11] - The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to SerpinPC for the treatment of hemophilia B, with or without inhibitors[11] About ORX750 (Orexin Agonist Program) ORX750 is an investigational, orally administered, highly potent and selective OX2R agonist for narcolepsy and sleep-wake disorders - ORX750 is an investigational, orally administered, highly potent and selective orexin receptor 2 (OX2R) agonist[3][26][33] - It is designed to directly target the underlying pathophysiology of orexin neuron loss in narcolepsy type 1 (NT1)[26] - Preclinical studies showed ORX750 potently activates the OX2R with an in vitro EC50 of 0.11 nM and 9,800-fold selectivity over the human orexin receptor (hOX1R)[26] About the LockBody Technology Platform and LB101 LockBody platform redefines immuno-oncology by selectively activating effector functions in the TME; LB101 is the lead candidate - Centessa's proprietary LockBody technology platform aims to redefine immuno-oncology treatment for patients with cancer by selectively driving potent effector function activity, such as CD47 or CD3, to the tumor micro-environment (TME) while avoiding systemic toxicity[12][34] - The first LockBody candidate is LB101, a conditionally tetravalent PD-L1xCD47 bispecific monoclonal antibody[27][34] - LB101's CD47 cell-killing mechanism is designed to be blocked by the PD-L1 tumor targeting domain until IgG-derived hinges are naturally degraded in the TME, unlocking and activating the CD47 effector function activity in the tumor[27] Forward-Looking Statements This section outlines risks and uncertainties related to product development, clinical trials, financing, and regulatory approvals - Forward-looking statements are based on current expectations, estimates, assumptions, and projections and are subject to risks and uncertainties that could cause actual results to differ materially and adversely[13][35] - Risks include those related to the safety and tolerability profile of product candidates, ability to recruit subjects for clinical trials, timely execution of IND-enabling activities, intellectual property protection, adequate financing, regulatory clearances, and broader economic and geopolitical risks[28][35] - The company explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law[28] Contact Information Provides contact details for investor relations inquiries - For investor relations inquiries, contact Kristen K. Sheppard, Esq., SVP of Investor Relations, at investors@centessa.com[14][28]