SerpinPC (APC-specific serpin) / Centessa - LARVOL DELTA

Rebalancing agents in hemophilia: knowns, unknowns, and uncertainties. (PubMed, Haematologica) - "Fitusiran is a small interfering RNA agent that reduces antithrombin synthesis in hepatocytes, favoring a procoagulant state. Other promising rebalancing agents are concizumab and marstacimab, which selectively bind to the K2 domain of the tissue factor pathway inhibitor, thus restoring thrombin generation. SerpinPC is a subcutaneous biological inhibitor that blocks the anticoagulant activated protein C pathway, while VGA039 is a monoclonal antibody that targets its cofactor protein S. Although the available clinical data are promising, several important challenges remain. These include the thrombotic risk of rebalancing agents, perioperative and bleeding management, availability in low-income countries, efficacy and FVIII equivalence compared to existing treatments, ideal target populations, and potential application in other hemostatic disorders. The primary aim of this review is to summarize the best available evidence on these novel rebalancing agents, while..."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Rebalancing therapy for congenital hemophilia (PubMed, Rinsho Ketsueki) - "The anti-TFPI agents concizumab and marstacimab are administered subcutaneously and have been approved for use in Japan. The siRNA drug fitusiran is used as an anti-AT agent that reduces the synthesis of AT, and SerpinPC as an anti-APC agent that specifically inhibits APC. This article will outline the concept of rebalancing therapy and the results of clinical trials, as well as precautions and potential issues during treatment."

Journal • Review • Hematological Disorders • Hemophilia • Rare Diseases

The preclinical profile of SerpinPC- a potential new treatment for hemophilia. (PubMed, Blood Adv) - "SerpinPC treatment was not associated with an increased inflammatory response and was well tolerated at high doses in WT animals. SerpinPC is currently being evaluated in persons with severe hemophilia."

Journal • Preclinical • Hematological Disorders • Hemophilia • Hemophilia A • Inflammation • Rare Diseases

PRESent-2: The Efficacy and Safety of SerpinPC in Participants with Severe Hemophilia a or Moderately Severe to Severe Hemophilia B (clinicaltrials.gov) - P2 | N=60 | Terminated | Sponsor: ApcinteX Ltd | Active, not recruiting ➔ Terminated; Study terminated due to business and strategic decision

Trial termination • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

PRESent-3: A Study of SerpinPC in Participants with Hemophilia B (HemB) with Inhibitors (clinicaltrials.gov) - P2 | N=3 | Terminated | Sponsor: ApcinteX Ltd | Active, not recruiting ➔ Terminated; Study terminated due to business and strategic decision

Trial termination • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

PRESent-6: The Long-term Safety and Efficacy of SerpinPC in Subjects with Hemophilia Who Completed a Sponsored SerpinPC Clinical Trial (clinicaltrials.gov) - P3 | N=15 | Terminated | Sponsor: ApcinteX Ltd | N=150 ➔ 15 | Trial completion date: Nov 2028 ➔ Jan 2025 | Recruiting ➔ Terminated | Trial primary completion date: Nov 2028 ➔ Jan 2025; Study terminated due to business and strategic decision.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Hemophilia Non-Interventional Study Prior to SerpinPC Intervention (PRESent-5) (clinicaltrials.gov) - P=N/A | N=108 | Terminated | Sponsor: ApcinteX Ltd | N=200 ➔ 108 | Recruiting ➔ Terminated; Study terminated due to business and strategic decision

Enrollment change • Trial termination • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

The Safety and Tolerability of SerpinPC in Healthy Men and in Men with Severe Blood Disorders (haemophilia a and B) (clinicaltrials.gov) - P1/2 | N=39 | Completed | Sponsor: ApcinteX Ltd | Active, not recruiting ➔ Completed

Trial completion • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

PRESent-3: A Study of SerpinPC in Participants with Hemophilia B (HemB) with Inhibitors (clinicaltrials.gov) - P2 | N=3 | Active, not recruiting | Sponsor: ApcinteX Ltd | Recruiting ➔ Active, not recruiting | N=12 ➔ 3 | Trial completion date: Oct 2025 ➔ Feb 2025 | Trial primary completion date: Sep 2025 ➔ Nov 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

PRESent-2: The Efficacy and Safety of SerpinPC in Participants with Severe Hemophilia a or Moderately Severe to Severe Hemophilia B (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: ApcinteX Ltd | Recruiting ➔ Active, not recruiting | N=120 ➔ 60 | Trial completion date: Jun 2026 ➔ Feb 2025 | Trial primary completion date: Mar 2026 ➔ Nov 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Rare Diseases

Centessa Pharmaceuticals Reports Financial Results for the Third Quarter of 2024 and Provides Business Update (GlobeNewswire) - "The Company has made a strategic and data-driven decision to discontinue the global clinical development of SerpinPC, a novel inhibitor of activated protein C that was being evaluated for the treatment of hemophilia B. This action was driven by the Company’s decision to prioritize capital toward the development of its OX2R agonist program and the outcome of a planned interim analysis of Part 1 of the PRESent-2 study of SerpinPC."

Discontinued • Genetic Disorders • Hemophilia • Hemophilia A • Hemophilia B

PRESent-6: The Long-term Safety and Efficacy of SerpinPC in Subjects With Hemophilia Who Completed a Sponsored SerpinPC Clinical Trial (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: ApcinteX Ltd

New P3 trial • Hematological Disorders • Hemophilia • Rare Diseases

SerpinPC: a potential non-factor treatment to prevent bleeding in hemophilia (WFH 2024) - No abstract available

Late-breaking abstract • Hematological Disorders • Hemophilia • Rare Diseases

SerpinPC in persons with severe haemophilia (PwH): updated results from a multicentre multi-part, first-in-human study (EAHAD 2024) - No abstract available

Clinical • P1 data • Hematological Disorders • Hemophilia • Rare Diseases

Serpin-PC in Persons with Severe Hemophilia (PwH): Updated Results from a Multicenter Multi-Part, First-in-Human Study (ASH 2023) - "Part 5 was a further extension in which subjects who completed Part 4 continued to receive 1.2 mg/kg of SerpinPC once every 2 weeks for 52 weeks. Results Annualized bleed rates, safety and tolerability for Part 5 will be available and a complete summary of all results to the end of Part 5 will be presented, including available pharmacokinetic and anti-drug antibody data."

Clinical • P1 data • Hematological Disorders • Hemophilia • Rare Diseases

PRESent-2: The Efficacy and Safety of SerpinPC in Participants With Severe Hemophilia A or Moderately Severe to Severe Hemophilia B (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: ApcinteX Ltd | Enrolling by invitation ➔ Recruiting

Enrollment status • Hematological Disorders • Hemophilia • Rare Diseases

PRESent-3: A Study of SerpinPC in Participants With Hemophilia B (HemB) With Inhibitors (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: ApcinteX Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Disorders • Hemophilia • Rare Diseases

PRESent-2: The Efficacy and Safety of SerpinPC in Participants With Severe Hemophilia A or Moderately Severe to Severe Hemophilia B (clinicaltrials.gov) - P2 | N=120 | Enrolling by invitation | Sponsor: ApcinteX Ltd | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Hematological Disorders • Hemophilia • Rare Diseases

Centessa Pharmaceuticals Receives Fast Track Designation from the U.S. FDA for SerpinPC for Hemophilia B (GlobeNewswire) - "Centessa Pharmaceuticals plc...today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to SerpinPC, an investigational novel inhibitor of activated protein C (APC) being developed for the treatment of hemophilia B, with or without inhibitors."

Fast track designation • Genetic Disorders • Hemophilia

The Use of Bypassing Treatment Strategies in Hemophilia and Their Effect on Laboratory Testing. (PubMed, Semin Thromb Hemost) - "Activated prothrombin complex concentrate was the original BPA, recombinant activated factor VII was then introduced, and more recently nonfactor agents that target the procoagulant and anticoagulant systems have been developed and are in clinical use (e.g., emicizumab, a bispecific antibody for hemophilia A). Other BPAs are in clinical trials (e.g., fitusiran targets antithrombin, concizumab and marstacimab target tissue factor pathway inhibitor, and SerpinPC targets activated protein C). The BPAs have a varied effect on coagulation assays, and as more patients are exposed to these agents, it is important to be aware of the effects. Herein, we present an overview of the effect of BPAs on routine and specialized coagulation assays including thrombin generation and viscoelastic assays."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

The Safety and Tolerability of SerpinPC in Healthy Men and in Men With Severe Blood Disorders (Haemophilia A and B) (clinicaltrials.gov) - P1/2 | N=39 | Active, not recruiting | Sponsor: ApcinteX Ltd | Trial completion date: Oct 2023 ➔ Oct 2024 | Trial primary completion date: Oct 2023 ➔ Oct 2024

Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Rare Diseases

PRESent-2: The Efficacy and Safety of SerpinPC in Participants With Severe Hemophilia A or Moderately Severe to Severe Hemophilia B (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: ApcinteX Ltd

New P2 trial • Hematological Disorders • Hemophilia • Rare Diseases

PRESent-3: A Study of SerpinPC in Participants With Hemophilia B (HemB) With Inhibitors (clinicaltrials.gov) - P2 | N=12 | Not yet recruiting | Sponsor: ApcinteX Ltd

New P2 trial • Hematological Disorders • Hemophilia • Rare Diseases

SERPINPC in persons with severe haemophilia (PWH): updated results from a multi-centre, multi-part, first-in-human study (EAHAD 2023) - No abstract available

Clinical • P1 data • Hematological Disorders • Hemophilia • Rare Diseases

Serpinpc in Persons with Severe Hemophilia (PwH): Updated Results from a Multi-Center, Multi-Part, First-in-Human Study (ASH 2022) - "The effects of length of treatment and exposure will be further examined in Parts 3-5. More clinical trials are planned to evaluate the benefit and risk profile of SerpinPC in PwH."

Clinical • P1 data • Dermatology • Hematological Disorders • Hemophilia • Rare Diseases