pelecopan (BCX9930) / BioCryst - LARVOL DELTA

Switching between complement inhibitors in patients with PNH: A real-world analysis of strategy, efficacy, and safety. (ASH 2025) - "In 2025, 3 C5 inhibitors (C5i) are approved (eculizumab (ECU), ravulizumab (RAV), crovalimab) & 3proximal inhibitors (PI) (pegcetacoplan (PEG), ipatacopan (IPTA), danicopan (DAN) plus C5i). Some clinicaltrial therapies have not continued development (vermicopan (VERM), BCX9930 (BCX), other C5i).PI clinical trials have protocols for changing from terminal to PI, based on drug half-life... Sixty-two pts from 8 countries were included with mean age at diagnosis 38.4 years (range 16-79)& mean Hb 87.8 g/L (missing data, n=17). Where reported indications for CI were hemolysis (49/62),hemolysis and thrombosis (5/62), thrombosis (3/62). Mean time on CI was 103.6 months (range 23-276; missing n=3) & mean granulocyte clone 86% (range 31-99; missing n=9).First-line CI were ECU/RAV (50/62), VERM (9/62) & investigational C5i (3/62)."

Clinical • Real-world • Real-world evidence • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

Long-term Safety of BCX9930 in Participants With Paroxysmal Nocturnal Hemoglobinuria (clinicaltrials.gov) - P2 | N=28 | Terminated | Sponsor: BioCryst Pharmaceuticals | Trial completion date: Feb 2026 ➔ Jan 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Feb 2026 ➔ Jan 2025; Sponsor decision

Monotherapy • Trial completion date • Trial primary completion date • Trial termination • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral Complement Factor D Inhibitor BCX9930 in Healthy Participants. (PubMed, J Clin Pharmacol) - "BCX9930 was safe and generally well tolerated in this first-in-human study and displayed highly favorable PK and PD profiles. These results support Factor D inhibition as a promising strategy for treatment of complement-mediated diseases."

Clinical • Journal • P1 data • PK/PD data

Urine complement analysis implies complement activation is involved in membranous nephropathy. (PubMed, Front Med (Lausanne)) - "The factor B inhibitor LNP023 and the factor D inhibitor BCX9930 are undergoing clinical trials for the treatment of MN. Our study indicates that complement abnormalities could serve as clinical biomarkers for tracking the progression of MN, predicting clinical remission, and guiding targeted complement therapy for those affected."

Journal • Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Renal Disease • CD59

A review of progress on complement and primary membranous nephropathy. (PubMed, Medicine (Baltimore)) - "Several clinical trials are presently underway to evaluate the efficacy of complement inhibitors, such as MASP2 antagonists (OMS721), C3 and C3b antagonists (APL2), FD inhibitors (BCX9930), C3aR antagonists (SB290157 and JR14a), FB inhibitors (LNP023). This article reviews the recent research progress on the role of the complement pathway in the pathogenesis of PMN, and underscores the importance of continued research into the complement pathway and its inhibitors, which may pave the way for groundbreaking advancements in the management of PMN."

Journal • Review • Glomerulonephritis • Nephrology • Renal Disease

A Long Term Safety Study of BCX9930 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH) (clinicaltrials.gov) - P2 | N=19 | Terminated | Sponsor: BioCryst Pharmaceuticals | N=200 ➔ 19 | Trial completion date: Jan 2025 ➔ Oct 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Oct 2024 ➔ Oct 2023; Sponsor decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

REDEEM-1: BCX9930 for Treatment of PNH in Subjects With Inadequate Response to C5 Inhibitor Therapy (clinicaltrials.gov) - P2 | N=12 | Terminated | Sponsor: BioCryst Pharmaceuticals | N=81 ➔ 12 | Trial completion date: Feb 2025 ➔ Sep 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2024 ➔ Sep 2023; Sponsor decision

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Trial termination • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

REDEEM-2: BCX9930 for the Treatment of PNH in Subjects Not Receiving Other Complement Inhibitor Therapy (clinicaltrials.gov) - P2 | N=12 | Terminated | Sponsor: BioCryst Pharmaceuticals | N=57 ➔ 12 | Trial completion date: Dec 2024 ➔ Sep 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2024 ➔ Sep 2023; Sponsor decision

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Trial termination • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Long-term Safety of BCX9930 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (clinicaltrials.gov) - P2 | N=28 | Active, not recruiting | Sponsor: BioCryst Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

FACTOR D INHIBITION WITH ORAL BCX9930 MONOTHERAPY LEADS TO SUSTAINED CONTROL OF HEMOLYSIS AND SYMPTOMS OVER 48 WEEKS IN SUBJECTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA NAÏVE TO C5 INHIBITORS (EHA 2022) - P1/2, P2 | "Conclusion BCX9930 at doses up to 500 mg BID was generally well-tolerated. Notable improvements from baseline to 48 weeks were observed in Hb, LDH, ARC, and fatigue scores, with concomitant increases in PNH RBC clone size. Proximal AP inhibition of Factor D by BCX9930 demonstrated sustained relief of anemia and fatigue, and freedom from transfusions, supporting ongoing pivotal trials of BCX9930 monotherapy for treatment of PNH."

Clinical • Monotherapy • Anemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Pain • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

FACTOR D INHIBITION WITH ORAL BCX9930 LEADS TO SUSTAINED CONTROL OF HEMOLYSIS AND SYMPTOMS OVER 48 WEEKS IN SUBJECTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA INADEQUATELY CONTROLLED ON C5 INHIBITORS (EHA 2022) - P1/2, P2 | "Notable improvements were observed from baseline to 48 weeks in Hb, ARC, and fatigue scores, with concomitant increases in PNH RBC clone size. Proximal AP inhibition of Factor D by BCX9930 in combination with C5 INH (with 3 of 4 subjects transitioning to monotherapy) led to sustained relief of anemia, fatigue, and reduction of transfusion burden, supporting ongoing pivotal trials of oral BCX9930 monotherapy for treatment of PNH."

Clinical • Anemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Pain • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

[VIRTUAL] BCX9930, A NOVEL ORAL FACTOR D INHIBITOR, HAS POSITIVE EFFECTS ON HEMOLYSIS AND CLINICAL OUTCOMES IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) NAÏVE TO COMPLEMENT INHIBITORS (EHA 2021) - P1/2 | "Improvements in fatigue were also observed. This study successfully identified a safe and tolerable BCX9930 dose range with dose-related meaningful clinical improvement, supporting progression to controlled clinical trials of BCX9930 in PNH."

Clinical • Clinical data • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Gastrointestinal Disorder • Hematological Disorders • Herpes Zoster • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis • Varicella Zoster

[VIRTUAL] BCX9930, AN ORAL FACTOR D INHIBITOR, CONTROLS EXTRAVASCULAR HEMOLYSIS AND ALLEVIATES ASSOCIATED SYMPTOMS IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA INADEQUATELY CONTROLLED ON C5 INHIBITORS (EHA 2021) - P1/2 | "Results Two patients are receiving ravulizumab and 4 eculizumab (>900mg every 2 weeks in 3). No serious or Grade 3 or 4 AEs were reported and there were no trends in safety laboratory values Conclusion Oral BCX9930 at doses up to 500mg BID was safe and generally well-tolerated over at least 58 days in PNH patients with inadequate response to a C5 inhibitor. Following initiation of BCX9930, notable improvements were observed in Hb, ARC, abundance of PNH RBC, fatigue scores and RBC transfusion requirements. Both proximal AP inhibition of Factor D and demonstrated improvements in hemolysis support future evaluation of BCX9930 monotherapy for patients who are inadequately responding to C5 inhibitors."

Clinical • Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

[VIRTUAL] BCX9930, an Oral Factor D Inhibitor, for the Potential Treatment of Alternative Pathway Mediated Diseases: Interim Results of a Phase 1 Study in Healthy Subjects (ASH 2020) - P1/2 | "The approved intravenously (IV) administered C5 inhibitors eculizumab and ravulizumab inhibit MAC formation and intravascular hemolysis, but do not inhibit opsonization, leading to extravascular hemolysis and potentially incomplete treatment response. BCX9930 is a potent and selective orally bioavailable inhibitor of human complement factor D. In this preliminary analysis of an ongoing FIH study, BCX9930 displayed a promising safety and tolerability profile. Exposure was approximately linear and dose-proportional across a wide dose range, and complete and durable suppression of the AP was achieved. Together, these findings support further evaluation of BCX9930 in patients with PNH and other AP-mediated diseases."

Clinical • P1 data • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • Nephrology • Pain • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • CD59

[VIRTUAL] BCX9930, a Potent, Selective, Oral Factor D Inhibitor, Demonstrates Proof-of-Concept As Monotherapy in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) (ASH 2020) - P1/2 | " Ongoing Study BCX9930-101 includes an open-label, dose-ranging evaluation of BCX9930 in PNH subjects who may either be naïve to C5 inhibitors (and receive BCX9930 as monotherapy) or have an incomplete treatment response to eculizumab or ravulizumab (with BCX9930 added to existing treatment)...One subject developed a rash during treatment with amoxicillin for an URTI; the rash resolved while continuing BCX9930 dosing. One subject on concomitant chronic corticosteroids and azathioprine had an unrelated fatal serious adverse event of disseminated varicella during the study extension... Oral BCX9930 elicited rapid changes in laboratory parameters indicative of reduced hemolysis and clinical benefit and was safe and generally well-tolerated over a 28-day dosing interval. These interim results establish proof of concept for monotherapy with BCX9930 in the treatment of C5-inhibitor naïve PNH patients and support evaluation of higher doses."

Clinical • Monotherapy • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Erectile Dysfunction • Fatigue • Hematological Disorders • Hepatology • Infectious Disease • Pain • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Respiratory Diseases • Thrombosis • Varicella Zoster

[VIRTUAL] Preclinical Characterization of BCX9930, a Potent Oral Complement Factor D Inhibitor, Targeting Alternative Pathway-Mediated Diseases Including Paroxysmal Nocturnal Hemoglobinuria (PNH) (ASH 2020) - P1/2 | "Inhibition of terminal complement C5 by eculizumab or ravulizumab results in sustained inhibition of intravascular hemolysis in patients with PNH by blocking formation of the membrane attack complex (C5b-9). BCX9930 inhibitory activity on Factor D in vitro was potent and highly specific. BCX9930 completely blocked hemolysis of PNH cells in vitro and suppressed the accumulation of C3 fragments on PNH erythrocytes, indicating that BCX9930 has the potential to inhibit both intravascular and extravascular hemolysis. After oral dosing of BCX9930 in rhesus monkeys, AP activity was completely suppressed in ex vivo assays."

Preclinical • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease

Long-term Safety of BCX9930 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: BioCryst Pharmaceuticals

Monotherapy • New P2 trial • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

REDEEM - access to BCX9930 (clinicaltrialsregister.eu) - P2 | N=200 | Ongoing | Sponsor: BioCryst Pharmaceuticals Inc

Monotherapy • New P2 trial • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

BCX9930 for the Treatment of C3G, IgAN, and PMN (RENEW) (clinicaltrials.gov) - P2 | N=2 | Terminated | Sponsor: BioCryst Pharmaceuticals | N=42 ➔ 2 | Trial completion date: Feb 2025 ➔ Sep 2022 | Recruiting ➔ Terminated | Trial primary completion date: Jan 2025 ➔ Sep 2022; Sponsor Decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Glomerulonephritis • IgA Nephropathy • Renal Disease

BCX9930 for the Treatment of C3G, IgAN, and PMN (RENEW) (clinicaltrials.gov) - P2 | N=42 | Recruiting | Sponsor: BioCryst Pharmaceuticals | Active, not recruiting ➔ Recruiting | Trial completion date: Jul 2023 ➔ Feb 2025 | Trial primary completion date: Jun 2023 ➔ Jan 2025

Enrollment open • Trial completion date • Trial primary completion date • Glomerulonephritis • IgA Nephropathy • Renal Disease

REDEEM-1: BCX9930 for Treatment of PNH in Subjects With Inadequate Response to C5 Inhibitor Therapy (clinicaltrials.gov) - P2 | N=81 | Recruiting | Sponsor: BioCryst Pharmaceuticals | Active, not recruiting ➔ Recruiting | Trial completion date: Oct 2023 ➔ Feb 2025 | Trial primary completion date: Apr 2023 ➔ Aug 2024

Enrollment open • Monotherapy • Trial completion date • Trial primary completion date • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

REDEEM-2: BCX9930 for the Treatment of PNH in Subjects Not Receiving Other Complement Inhibitor Therapy (clinicaltrials.gov) - P2 | N=57 | Recruiting | Sponsor: BioCryst Pharmaceuticals | Active, not recruiting ➔ Recruiting | Trial completion date: Aug 2023 ➔ Dec 2024 | Trial primary completion date: Nov 2022 ➔ Mar 2024

Enrollment open • Monotherapy • Trial completion date • Trial primary completion date • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

HOW WE (WILL) TREAT PNH? (EHOC 2022) - "Crovalimab, binding on the single missense C5 heterozygous mutation is injected s.c. monthly; two large phase III trials are ongoing as add on- and mono-therapy. Others, such as Pozelimab, injected subcutaneously on a weekly basis after an initial IV loading dose or Tesidolumab are still under current investigation...In a recent phase III trial, pegcetacoplan showed superiority to eculizumab in hemoglobin change from baseline and is now approved by the FDA for patients with PNH who are either treatmentnaive or switching from antiC5 monoclonal antibodies. Danicopan is an oral first- inclass factor D complement alternative pathway inhibitor and decreased significantly transfusion requirement, as shown in a phase II trial (phase III ongoing). BCX9930, another FD inhibitor in early development is given orally and demonstrated initial clinical efficacy both as addon therapy in patients with inadequate response to eculizumab as well as in monotherapy in treatmentnaive..."

Anemia • Bone Marrow Transplantation • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis • Transplantation • CFB

"$BCRX BioCryst Resumes Enrollment in BCX9930 Clinical Program https://t.co/kpJ5oI7dEy" (@stock_titan)

Clinical

Complement System as a New Target for Hematopoietic Stem Cell Transplantation-Related Thrombotic Microangiopathy. (PubMed, Pharmaceuticals (Basel)) - "Thus, it seems reasonable to propose complement inhibition therapy only to those patients exhibiting a clear complement activation according to the available biomarkers. Several agents are now available to inhibit complement activity: two drugs have been successfully used in TA-TMA, particularly in pediatric cases (eculizumab and narsoplimab) and others are at different stages of development (ravulizumab, coversin, pegcetacoplan, crovalimab, avacopan, iptacopan, danicopan, BCX9930, and AMY-101)."

Journal • Review • Bone Marrow Transplantation • Cardiovascular • Hematological Disorders • Hypertension • Infectious Disease • Pediatrics • Thrombosis • Transplantation