Hemophilia Program: Ongoing registrational PRESent-2 and PRESent-3 studies of SerpinPC for the treatment of hemophilia B; PRESent-2 interim analysis planned in 2024 Orexin Agonist Program: Cleared IND and initiated Phase 1 first-in-human clinical trial of ORX750, a highly potent and selective OX2R agonist for the treatment of narcolepsy; Clinical proof-of-concept data in acutely sleep-deprived healthy volunteers planned in 2H of 2024 LockBody® Technology Platform: Ongoing Phase 1/2a study of LB101 (PD-L1xCD47) for the treatment of solid tumors Cash runway, extended by recent public offering, supports clinical plans through multiple data readouts BOSTON and LONDON, May 13, 2024 (GLOBE NEWSWIRE) -- Centessa Pharmaceuticals plc (NASDAQ:CNTA), a clinical-stage pharmaceutical company that aims to discover and develop medicines that are transformational for patients, today reported financial results and business highlights for the first quarter ended March 31, 2024. "2024 is off to a strong start for Centessa. Following clearance of our IND, we recently initiated the Phase 1 first-in-human, clinical trial of ORX750, a highly potent and selective orexin receptor 2 (OX2R) agonist for the treatment of narcolepsy, and remain on track with our goal to share proof-of-concept data in acutely sleep-deprived healthy volunteers in the second half of this year," said Saurabh Saha MD PhD, Chief Executive Officer of Centessa. "We believe this study has the potential to deliver robust translational results that could lay the foundation for an orexin agonist clinical development program targeting narcolepsy Type 1 and Type 2 with the potential to expand into other sleep-wake disorders including idiopathic hypersomnia, as well as broader neurological indications. Additionally, the PRESent registrational studies for SerpinPC for the treatment of hemophilia B are progressing, and we plan to conduct an interim analysis of the PRESent-2 study later this year." Dr. Saha continued, "We are thrilled to now be progressing all three of our most advanced pipeline programs in clinical studies focused on areas with significant unmet need, including hemophilia B, sleep-wake disorders, and solid tumors. With our recently strengthened balance sheet, we believe we are well positioned to execute on our clinical plans through multiple clinical readouts." Recent Highlights In April and May, the Company completed an underwritten public offering of 12,390,254 American Depositary Shares ("ADSs") in the aggregate, at a price to the public of $9.25 per ADS, resulting in net proceeds of approximately $107.2 million, which included the underwriters' over-allotment option to purchase additional shares. In April, the Company announced that the U.S. Food and Drug Administration (FDA) cleared the Investigational New Drug application (IND) to initiate a Phase 1 first-in-human (FIH), clinical trial of ORX750 for the treatment of narcolepsy. In February, the Company presented data from the third year (Part 5) of the ongoing Phase 2a study of SerpinPC, an investigational subcutaneously administered novel inhibitor of activated protein C (APC) for the treatment of hemophilia, during an oral presentation at the European Association for Haemophilia and Allied Disorders (EAHAD). Part 5 data from the Phase 2a study showed a continued favorable safety and tolerability profile for SerpinPC, as well as sustained long-term efficacy results, as measured by a 96% reduction in the median all-bleed annualized bleeding rate (ABR) from the prospective baseline measured during the pre-exposure observation period. To date, there have been no thromboembolic events and no treatment-related sustained elevations of D-dimer observed throughout the Phase 2a study. Anticipated Upcoming Program Milestones Hemophilia Program - The registrational PRESent-2 (moderately severe to severe hemophilia B without inhibitors, and severe hemophilia A with or without inhibitors) and PRESent-3 (hemophilia B with inhibitors) studies of SerpinPC are ongoing. For PRESent-2, the Company plans to review Part 1 data in 2024 (interim analysis) with the goal of confirming a dose and advancing to Part 2 of the study. The primary endpoint of the PRESent-2 study is the rate of treated bleeds (expressed as ABR) during the first 24 weeks of treatment with SerpinPC (Part 2) compared to the observation period. The Company plans to share Part 1 data at a medical conference in late 2024 or early 2025. Orexin Agonist Program - The Phase 1 FIH clinical study of ORX750, which is being progressed for the treatment of narcolepsy, has been initiated. The Company expects to share clinical proof-of-concept data in acutely sleep-deprived healthy volunteers in 2H of 2024. LockBody Technology Platform - The Phase 1/2a FIH clinical study of LB101 (PD-L1xCD47 LockBody) for the treatment of solid tumors is ongoing. Where applicable, the Company plans to provide updates on preclinical assets including follow-up orexin agonists and LB206, a PD-L1xCD3 LockBody, when they advance toward clinical studies. First Quarter 2024 Financial Results Cash, Cash Equivalents and Short-term Investments: $230.2 million as of March 31, 2024. The Company expects its cash, cash equivalents and short-term investments as of March 31, 2024, in combination with approximately $107.2 million in aggregate net proceeds from our offering of ADSs completed in April and May 2024, will fund operations into mid-2026, without drawing on the remaining available tranches under the Oberland credit facility. Research & Development Expenses: $22.7 million for the first quarter ended March 31, 2024, compared to $32.8 million for the first quarter ended March 31, 2023. General & Administrative Expenses: $13.4 million for the first quarter ended March 31, 2024, compared to $16.1 million for the first quarter ended March 31, 2023. Net Loss Attributable to Ordinary Shareholders: $38.0 million for the first quarter ended March 31, 2024, compared to $50.7 million for the first quarter ended March 31, 2023. About Centessa Pharmaceuticals Centessa Pharmaceuticals plc is a clinical-stage pharmaceutical company that aims to discover and develop medicines that are transformational for patients. Our most advanced programs include a hemophilia program, an orexin agonist program for the treatment of narcolepsy and other sleep-wake disorders, and an immuno-oncology program focused on our LockBody® technology platform. We operate with the conviction that each of our programs has the potential to change the current treatment paradigm and establish a new standard of care. For more information, visit www.centessa.com, which does not form part of this release. About SerpinPC SerpinPC is an investigational, subcutaneously administered novel inhibitor of APC being developed as a potential treatment for hemophilia, regardless of severity or inhibitor status, and which may also be developed to prevent bleeding associated with other bleeding disorders. The registrational program for SerpinPC in hemophilia B includes a set of clinical studies with multiple components. PRESent-5 is an observational feeder study to collect prospective observational data for minimum defined periods before switching to dosing subjects in the interventional studies. The interventional studies include PRESent-2 (moderately severe to severe hemophilia B without inhibitors, and severe hemophilia A with or without inhibitors) and PRESent-3 (hemophilia B with inhibitors). Additional information on the trials can be accessed at www.clinicaltrials.gov (NCT05605678, NCT05789524, NCT05789537). 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. SerpinPC has not been approved by the FDA or any other regulatory authority for any use. About ORX750 Centessa's first orexin development candidate is ORX750, an investigational, orally administered, highly potent and selective orexin receptor 2 (OX2R) agonist designed to directly target the underlying pathophysiology of orexin neuron loss in narcolepsy type 1 (NT1), with potential applicability to narcolepsy type 2 (NT2), idiopathic hypersomnia (IH), and other sleep-wake disorders with normal orexin levels. ORX750 has been shown in preclinical studies to potently activate the OX2R with an in vitro EC50 of 0.11 nM and 9,800-fold selectivity over the human orexin receptor (hOX1R). ORX750 is in a Phase 1 clinical study for the treatment of narcolepsy. ORX750 has not been approved by the FDA or any other regulatory authority. About the LockBody Technology Platform and LB101 Centessa's proprietary LockBody technology platform aims to redefine immuno-oncology treatment for patients with cancer. LockBody drug candidates are designed to selectively drive potent effector function activity, such as CD47 or CD3, to the tumor micro-environment (TME) while avoiding systemic toxicity. Centessa's first LockBody candidate is LB101, a conditionally tetravalent PD-L1xCD47 bispecific monoclonal antibody which has two anti-CD47 domains blocked by two anti-PD-L1 domains, with proprietary human IgG-derived hinges linking the anti-CD47 and anti-PD-L1 domains. The cell-killing mechanism of action, CD47, is designed to be blocked by the PD-L1 tumor targeting domain until the IgG-derived hinges are naturally degraded in the TME, thus unlocking and activating the CD47 effector function activity in the tumor. LB101 is in a Phase 1/2a clinical trial. Additional information on the trial can be accessed at www.clinicaltrials.gov (NCT05821777). LB101 is an investigational agent that has not been approved by the FDA or any other regulatory authority. Forward Looking Statements This press release contains forward-looking statements. These statements may be identified by words such as "may," "might," "will," "could," "would," "should," "expect," "intend," "plan," "objective," "anticipate," "believe," "estimate," "predict," "potential," "continue," "ongoing," "aim," "seek," and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements, including statements related to the Company's ability to discover and develop transformational medicines for patients; its expectations for executing on the Company's pipeline; its expectations on its anticipated cash runway; the timing of commencement of new studies or clinical trials or clinical and preclinical data related to SerpinPC, LB101, other LockBody candidates, the LockBody technology platform, ORX750 and other orexin agonist molecules; its ability to identify, screen, recruit and maintain a sufficient number of or any subjects in its existing and anticipated studies or clinical trials including PRESent-5, the observational feeder study, PRESent-2 and PRESent-3 and studies or trials of LB101 and any other LockBody candidates, ORX750 and other orexin agonist molecules and its expectations on executing its research and clinical development plans and the timing thereof; the Company's ability to differentiate SerpinPC, LB101, other LockBody candidates, ORX750 and other orexin agonist molecules from other treatment options; the development, design and therapeutic potential of SerpinPC, LB101, other LockBody candidates, the LockBody technology platform, ORX750 and other orexin agonist molecules; and regulatory matters, including the timing and likelihood of success of obtaining regulatory clearance, obtaining authorizations to initiate or continue clinical trials. Any forward-looking statements in this press release are based on our current expectations, estimates, assumptions and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to ...