Principia Biopharma is a biopharmaceutical corporation that specializes in creating oral therapies for patients with significant medical needs in immunology and oncology. The company utilizes its Tailored Covalency platform to develop small molecule inhibitors of enzymes and receptor ligands that are as effective as injectable biologics but can be taken orally. Their product pipeline includes PRN1008, PRN2246, PRN1371, and an immunoproteasome inhibitor. Founded by Jack Taunton and Richard A. Miller in 2008, the company is headquartered in South San Francisco, California.

Tags

Immune System Diseases

Congenital Disorders

Skin and Musculoskeletal Diseases

Small molecule drug

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Immune System Diseases	5
Hemic and Lymphatic Diseases	1
Neoplasms	1

Top 5 Drug Type	Count

Small molecule drug	6

Top 5 Target	Count

BTK(Tyrosine-protein kinase BTK)	2
PSMB8(proteasome 20S subunit beta 8)	1
FGFRs(Fibroblast growth factor receptors)	1
PSMB8 x PSMB9	1
ITK(Tyrosine-protein kinase ITK/TSK)	1

Drugs associated with Principia Biopharma, Inc.

Rilzabrutinib

Target

BTK

Mechanism

BTK inhibitors

Active Org.

Sanofi (China) Investment Co. Ltd. [+4]

Originator Org.

Principia Biopharma, Inc.

Active Indication

Purpura, Thrombocytopenic, Idiopathic [+8]

Inactive Indication

Hepatic Insufficiency [+1]

Drug Highest PhasePhase 3

First Approval Ctry. / Loc.-

First Approval Date-

Atuzabrutinib

Target

BTK

Mechanism

BTK inhibitors

Active Org.

Principia Biopharma, Inc.

Originator Org.

Principia Biopharma, Inc.

Active Indication

Dermatitis, Atopic

Inactive Indication

Arthritis [+1]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date-

PRN694

Target

ITK

Mechanism

ITK inhibitors

Active Org.

Principia Biopharma, Inc.

Originator Org.

Principia Biopharma, Inc.

Active Indication

Autoimmune Diseases

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date-

Clinical Trials associated with Principia Biopharma, Inc.

CTR20220433 / CompletedPhase 1

一项在中国健康男性和女性受试者中评价Rilzabrutinib （PRN1008/ SAR444671）的药代动力学、安全性和耐受性的Ⅰ期、单中心、开放标签研究

[Translation] A Phase I, single-center, open-label study to evaluate the pharmacokinetics, safety, and tolerability of Rilzabrutinib (PRN1008/SAR444671) in healthy Chinese male and female subjects

主要目的：在中国健康受试者中评价rilzabrutinib单次给药的药代动力学（PK）；次要目的：在中国健康受试者中评估rilzabrutinib单次给药的安全性和耐受性

[Translation]

Primary objective: To evaluate the pharmacokinetics (PK) of a single dose of rilzabrutinib in healthy Chinese subjects; Secondary objective: To evaluate the safety and tolerability of a single dose of rilzabrutinib in healthy Chinese subjects

Start Date23 Mar 2023

Sponsor / Collaborator

Patheon, Inc.

[+3]

CTR20220447 / RecruitingPhase 3

一项评估持续或慢性免疫性血小板减少症（ITP）成人和青少年口服Rilzabrutinib（PRN1008）的疗效和安全性的包含开放标签扩展期的Ⅲ期、多中心、随机化、双盲、安慰剂对照、平行组研究

[Translation] A Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study with an open-label extension to evaluate the efficacy and safety of oral Rilzabrutinib (PRN1008) in adults and adolescents with persistent or chronic immune thrombocytopenia (ITP)

主要疗效目的基于在24周盲态治疗期的最后12周中的至少8周能够达到血小板计数≥50,000/μL的成人患者比例，证明rilzabrutinib与安慰剂相比在难治性/复发性ITP患者中的疗效。关键次要疗效目的评价在不使用补救治疗的情况下，rilzabrutinib与安慰剂相比在24周盲态治疗期内血小板计数≥50,000/μL或≥30,000/μL且<50,000/μL并且相对于基线水平至少加倍的周数方面的作用。评价在不使用补救治疗的情况下，rilzabrutinib与安慰剂相比在24周盲态治疗期内血小板计数≥30,000/μL且<50,000/μL并且相对于基线水平至少加倍的周数方面的作用。评价rilzabrutinib与安慰剂相比在至首次血小板计数≥50,000/μL或≥30,000/μL且<50,000/μL并且相对于基线水平至少加倍的时间方面的作用。评价rilzabrutinib与安慰剂相比在需要使用补救治疗的患者比例方面的作用。评价rilzabrutinib与安慰剂相比在特发性血小板减少性紫癜出血评估量表（IBLS）评估较基线的变化方面的作用。

[Translation]

Primary efficacy objective To demonstrate the efficacy of rilzabrutinib compared with placebo in patients with refractory/relapsed ITP based on the proportion of adult patients who were able to achieve platelet counts ≥50,000/μL for at least 8 of the last 12 weeks of the 24-week blinded treatment period. Key secondary efficacy objectives To evaluate the effect of rilzabrutinib compared with placebo in the number of weeks with platelet counts ≥50,000/μL or ≥30,000/μL and <50,000/μL and at least doubling from baseline during the 24-week blinded treatment period without the use of rescue therapy. To evaluate the effect of rilzabrutinib compared with placebo in the number of weeks with platelet counts ≥30,000/μL and <50,000/μL and at least doubling from baseline during the 24-week blinded treatment period without the use of rescue therapy. To evaluate the effect of rilzabrutinib compared with placebo on the time to first platelet count ≥50,000/μL or ≥30,000/μL and <50,000/μL that at least doubled from baseline. To evaluate the effect of rilzabrutinib compared with placebo on the proportion of patients requiring rescue therapy. To evaluate the effect of rilzabrutinib compared with placebo on the change from baseline in the Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS) assessment.

Start Date26 Jun 2022

Sponsor / Collaborator

Principia Biopharma, Inc.

[+3]

NCT04992546 / CompletedPhase 2

A Randomized, Intra-patient, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Topically Administered PRN473 (SAR444727) in Patients With Mild to Moderate Atopic Dermatitis

This was a Ph2a study that consists of a double-blind, intra-patient placebo-controlled treatment period and an open-label uncontrolled treatment period with objective to evaluate the safety, tolerability, PK and preliminary efficacy of PRN473 in up to 40 patients with mild to moderate AD.
On Day 1 (Baseline) of the Blinded Period, 2 target lesions with a difference no greater than 1 point in Total Sign Score (TSS) were randomly assigned to treatment in an intra-patient 1:1 manner, one lesion to PRN473 and the other to matching placebo.
Participation took approximately 13 weeks, including up to a 5-week screening period, a 6-week treatment period, end of study assessments 1 day after last dose, and a safety follow-up phone call 2 weeks after last dose.

Start Date13 Aug 2021

Sponsor / Collaborator

Principia Biopharma, Inc.

100 Clinical Results associated with Principia Biopharma, Inc.

0 Patents (Medical) associated with Principia Biopharma, Inc.

Literatures (Medical) associated with Principia Biopharma, Inc.

05 Nov 2021·Blood

Updated Phase I/II Safety and Efficacy Results for Oral Bruton Tyrosine Kinase Inhibitor Rilzabrutinib in Patients with Relapsed/Refractory Immune Thrombocytopenia

Author: Sourdille, Timothee ; Thomas, Dolca ; Daak, Ahmed ; Tzvetkov, Nikolay ; Efraim, Merlin ; Kostal, Milan ; Choi, Philip ; Yao, Mengjie ; Kaplan, Zane ; Kuter, David J. ; Gernsheimer, Terry ; Mayer, Jiří ; Jansen, A.J. Gerard ; McDonald, Vickie ; Iqbal, Fareha ; Baker, Ross ; Bandman, Olga ; Burns, Regan ; Ghanima, Waleed ; Gumulec, Jaromir ; Arora, Puneet ; Bird, Robert J. ; Cooper, Nichola ; Garg, Mamta ; Neale, Ann

AbstractIntroduction: Key characteristics of immune thrombocytopenia (ITP) include immune-mediated platelet destruction/impaired production, with resultant thrombocytopenia and increased bleeding risk. Durable response to current therapies remains an unmet need, particularly in the relapsed/refractory setting. Rilzabrutinib is the first oral, reversible, covalent inhibitor of Bruton tyrosine kinase designed to target immune-mediated pathways in ITP without inhibiting normal platelet aggregation. Initial phase I/II results in ITP demonstrated rapid and durable efficacy with rilzabrutinib that was well-tolerated at all dose levels, including the optimal 400 mg bid dose. Interim results on rilzabrutinib effects in patients with relapsed/refractory ITP were previously reported. Here we present long-term data from a larger group of patients who initiated rilzabrutinib at 400 mg bid and are continuing in the long-term extension (LTE) period.Methods: This ongoing, global phase I/II study (NCT03395210) enrolled adult patients from 8 countries with relapsed or refractory ITP who previously responded to ≥1 prior ITP therapy. Eligible patients with 2 baseline platelet counts of <30×10 9/L no less than 7 days apart in the 15 days before baseline received oral rilzabrutinib at starting doses of 200 or 400 mg QD, 300 or 400 mg bid for 24 weeks; intrapatient dose escalation was permitted to improve efficacy. Stable doses of concomitant corticosteroids and thrombopoietin receptor agonists were allowed for patients with inadequate platelet response. The primary endpoints were safety and achievement of ≥2 consecutive platelet counts ≥50×10 9/L and increased ≥20×10 9/L from baseline without rescue medication. Responding patients could continue in the LTE period with rilzabrutinib at the optimal 400 mg bid dose.Results: As of June 1, 2021 in 60 patients, 45 patients initiated rilzabrutinib 400 mg bid and to date, 16 patients with durable, stable response proceeded to LTE at 400 mg bid. At enrollment for patients initiating rilzabrutinib 400 mg bid, median age was 49 y (range, 19-74), median duration of ITP was 6.1 y (range, 0.4-52.5), and median platelet count was 15×10 9/L (range, 2-33×10 9/L). Patients were heavily pretreated with a median of 6 prior treatment events (range, 1-53), including 24% with prior splenectomy. Overall, 18/45 patients (40%) achieved the primary endpoint. In primary responders, platelet counts of ≥30×10 9/L, ≥30×10 9/L with ≥20×10 9/L above baseline, and ≥50×10 9/L were maintained for a median of 95%, 86%, and 72% of weeks, respectively. Median time to first platelet counts of ≥30×10 9/L, ≥30×10 9/L with ≥20×10 9/L above baseline, and ≥50×10 9/L were 8.5 (7-134), 11.5 (7-134), and 12.5 (8-142) days, respectively. According to subgroup analyses, primary platelet responses were consistently >30% irrespective of baseline platelet counts, the use of concomitant therapy, duration of ITP, or number of prior therapies (Table). LTE patients received rilzabrutinib for an overall median duration of 462 days (range, 303-764). At LTE entry, patients had a median platelet count of 87×10 9/L (range, 16-321×10 9/L). In addition to all LTE patients achieving the primary endpoint during the main treatment period, these patients maintained platelet counts of ≥30×10 9/L, ≥30×10 9/L with ≥20×10 9/L above baseline, and ≥50×10 9/L, for a median of 100%, 96%, and 90%, of weeks, respectively, during the LTE period (Figure). Treatment-related treatment-emergent adverse events (TEAEs; all grade 1/2) were reported in 27/45 patients (60%); the most common were 36% diarrhea and 31% nausea, and all others were <10%. Only 3 patients had grade 1/2 treatment-related TEAEs during the LTE period, supporting a favorable safety profile with longer treatment. There were two related grade 1 bleeding events (conjunctival hemorrhage and contusion), two related grade 2 infections that resolved on treatment (erysipelas during the main treatment period and upper respiratory tract infection during the LTE), but no related thrombotic events or deaths.Conclusion: Oral rilzabrutinib 400 mg bid was well-tolerated and had durable, clinically significant platelet responses across subgroups and with extended treatment in patients with heavily pretreated ITP. Continued study in the ongoing, randomized phase III LUNA3 trial (NCT04562766) will further assess the magnitude and durability of rilzabrutinib's clinical benefit in ITP.Figure 1 Figure 1.DisclosuresKuter: Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, Bristol Myers Squibb (BMS), Immunovant, Kezar, Principia, Protalex, Rigel, Takeda (Bioverativ), UCB: Research Funding; Up-to-Date: Patents & Royalties: Up-To-Date; Rubius: Current equity holder in publicly-traded company; Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, BioCryst, Bristol Myers Squibb (BMS), Caremark, CRICO, Daiichi Sankyo, Dova, Genzyme, Immunovant, Incyte, Kyowa-Kirin, Merck Sharp Dohme, Momenta, Novartis, Pfizer, Principia, Protalex, Protalix, Rigel: Consultancy, Other: grant support and consulting fees; Platelet Disorder Support Association: Membership on an entity's Board of Directors or advisory committees. Mayer: Principia: Research Funding. Jansen: 3SBIO, Novartis: Other: Travel, accomodations, expenses; Advisory Board Novartis: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Other: Travel, Accommodations, Expenses. McDonald: Bayer, Sobi, Novartis, Amgen, argenx: Honoraria; Grifols: Research Funding. Baker: Roche, Janssen-Celeg: Membership on an entity's Board of Directors or advisory committees; Bayer, Takeda, Pfizer, Daiichi Sankyo, CSL Behring, Roche, Amgen, Celgene, Rigel Pharmaceuticals, Abbvie, Sanofi, MorphoSys AG, Acerta Pharma, Jansen-Cileg, Bristol-Myers Squibb, Boehringer Ingelheim, Portola, Technoclone, Alexion: Research Funding. Bird: Novartis, Amgen: Speakers Bureau. Garg: Amgen Janssen Novartis Sanofi Takeda: Honoraria; Takeda Janssen Novartis Sanofi: Other: Travel Accommodations, Expenses; University Hospital Leicester: Current Employment. Gernsheimer: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: personal fees ; Amgen: Honoraria; Cellphire: Consultancy; Dova: Consultancy, Honoraria; Principia: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Membership on an entity's Board of Directors or advisory committees, Research Funding; NHLBI: Research Funding. Ghanima: Amgen, Novartis, Pﬁzer, Principia Biopharma Inc- a Sanoﬁ Company, Sanoﬁ, SOBI, Griffols, UCB, Argenx: Consultancy; Amgen, Novartis, Pﬁzer, Bristol Myers Squibb, SOBI, Griffols, Sanoﬁ: Honoraria; Bayer, BMS/Pﬁzer: Research Funding. Bandman: Sanofi: Ended employment in the past 24 months. Arora: Principia Biopharma Inc, a Sanofi Company: Ended employment in the past 24 months. Burns: Sanofi: Ended employment in the past 24 months. Yao: Sanofi: Current Employment. Daak: Sanofi: Current Employment. Sourdille: Sanofi: Current Employment. Thomas: Chinook and Equillium Biopharma: Current holder of individual stocks in a privately-held company; Chinook: Membership on an entity's Board of Directors or advisory committees; Equillium Biopharma: Current Employment; Principia, a Sanofi Company: Ended employment in the past 24 months; Equillium Biopharma: Current equity holder in publicly-traded company. Neale: Principia Biopharma/Sanofi: Ended employment in the past 24 months; Principia Biopharma: Divested equity in a private or publicly-traded company in the past 24 months. Cooper: Sanofi and Principia: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations expenses; Principia and Sanofi: Consultancy.OffLabel Disclosure:Rilzabrutinib is an investigational therapy being evaluated in a clinical study for the treatment of patients with immune thrombocytopenia.

05 Nov 2021·Blood

LUNA3 Phase III Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of the Oral BTK Inhibitor Rilzabrutinib in Adults and Adolescents with Persistent or Chronic Immune Thrombocytopenia

Author: Bandman, Olga ; Cooper, Nichola ; Arora, Puneet ; Burns, Regan ; Lambert, Michele P. ; Neale, Ann ; Bussel, James B ; Kuter, David J. ; Liebman, Howard ; Yao, Mengjie ; Gernsheimer, Terry ; Ghanima, Waleed ; Tarantino, Michael D

AbstractBackground: The autoimmune disorder immune thrombocytopenia (ITP) is characterized by immune-mediated platelet destruction and impaired production, leading to a predisposition to bleeding and diminished quality of life. Although initially responsive to standard therapy, most patients do not attain durable remission or are challenged by long-term tolerability. Rilzabrutinib is the first oral, reversible Bruton tyrosine kinase (BTK) inhibitor that targets mechanisms driving ITP without effects on normal platelet aggregation. Preclinical studies showed simultaneous rapid anti-inflammatory effects of rilzabrutinib and neutralization and prevention of autoantibody signaling (Langrish J Immunol 2021). In an ongoing phase I/II study, the optimal dose of 400 mg bid rilzabrutinib (± concomitant ITP therapy) was well tolerated and resulted in rapid and durable platelet response across several subgroups of patients and with extended treatment.Study Design and Methods: LUNA3 is the first randomized, multicenter, phase III study evaluating the efficacy and safety of rilzabrutinib vs placebo with open-label extension in adult and adolescent patients with persistent or chronic ITP (NCT04562766; EudraCT 2020-002063-60). Eligible patients must have primary ITP for >6 months if aged 12-17 years or >3 months if aged ≥18 years and an average of 2 platelet counts <30×10 9/L (no single count >35×10 9/L) within 2 weeks prior to study treatment. Additionally, patients should have a previous response (platelet count ≥50×10 9/L) to corticosteroids or intravenous immunoglobulin/anti-D that was insufficient or not sustained, or documented intolerance or insufficient response to any appropriate courses of standard-of-care ITP therapy. Randomization is carried out separately for the 2 age groups (12-17 years and ≥18 years), and then patients are stratified by splenectomy status (yes/no) and thrombocytopenia severity (platelet counts <15×10 9/L or ≥15×10 9/L; Figure). Patients are randomized 2:1 to oral rilzabrutinib 400 mg bid or placebo to receive double-blind treatment for up to 24 weeks, followed by open-label treatment for 28 weeks, and then a 4-week safety follow-up. After the 12-week double-blind treatment, patients who are no longer responding (ie, platelet counts <30×10 9/L or <20×10 9/L above baseline on two consecutive visits) have the option to receive open-label rilzabrutinib or discontinue from the study. Concomitant stable doses of ITP medication (corticosteroids and/or thrombopoietin receptor agonists) are permitted if they were maintained for ≥2 weeks prior to study day 1. Patients who receive rescue medication are allowed to continue study treatment. The primary endpoint is the achievement of platelet counts ≥50×10 9/L for ≥8 of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue medication. Secondary endpoints include safety, duration of and time to platelet responses, rescue therapy use, and changes from baseline in ITP Bleeding Scale (IBLS) scores. Responders who had platelet counts ≥50×10 9/L or ≥30×10 9/L and at least doubled from baseline at ≥50% of visits without receiving rescue therapy during the last 8 weeks of the open-label period may enter an additional 12-month long-term extension. This clinical trial was initiated in 2020, with the planned enrollment goal of approximately 194 adult and 30 adolescent patients globally. The study results will provide further support for a unique treatment mechanism via BTK inhibition to target the underlying pathology of ITP.Figure 1 Figure 1.DisclosuresKuter: Platelet Disorder Support Association: Membership on an entity's Board of Directors or advisory committees; Up-to-Date: Patents & Royalties: Up-To-Date; Rubius: Current equity holder in publicly-traded company; Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, BioCryst, Bristol Myers Squibb (BMS), Caremark, CRICO, Daiichi Sankyo, Dova, Genzyme, Immunovant, Incyte, Kyowa-Kirin, Merck Sharp Dohme, Momenta, Novartis, Pfizer, Principia, Protalex, Protalix, Rigel: Consultancy, Other: grant support and consulting fees; Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, Bristol Myers Squibb (BMS), Immunovant, Kezar, Principia, Protalex, Rigel, Takeda (Bioverativ), UCB: Research Funding. Bussel: CSL: Other: DSMB; UCB: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Dova/Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; UptoDate: Honoraria; RallyBio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Principia/Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Momenta/Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cooper: Principia and Sanofi: Consultancy; Sanofi and Principia: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations expenses. Gernsheimer: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: personal fees ; Amgen: Honoraria; Cellphire: Consultancy; Dova: Consultancy, Honoraria; Principia: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Membership on an entity's Board of Directors or advisory committees, Research Funding; NHLBI: Research Funding. Lambert: Dova: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Principia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; PDSA: Research Funding; ClinGen, ISTH, ASH, GW University: Honoraria; Argenx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sysmex: Research Funding; Bayer: Consultancy; Octapharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Liebman: Sanofi, Momenta: Research Funding; Alexion, Novartis, Dova: Consultancy. Tarantino: Grifols: Research Funding, Speakers Bureau; Novo Nordisk: Research Funding; Pfizer: Research Funding; Principia: Membership on an entity's Board of Directors or advisory committees, Research Funding; Spark Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; UCB: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dova: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sobi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BioMarin: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees. Bandman: Sanofi: Ended employment in the past 24 months. Arora: Principia Biopharma Inc, a Sanofi Company: Ended employment in the past 24 months. Neale: Principia Biopharma: Divested equity in a private or publicly-traded company in the past 24 months; Principia Biopharma/Sanofi: Ended employment in the past 24 months. Burns: Sanofi: Ended employment in the past 24 months. Yao: Sanofi: Current Employment. Ghanima: Amgen, Novartis, Pﬁzer, Principia Biopharma Inc- a Sanoﬁ Company, Sanoﬁ, SOBI, Griffols, UCB, Argenx: Consultancy; Bayer, BMS/Pﬁzer: Research Funding; Amgen, Novartis, Pﬁzer, Bristol Myers Squibb, SOBI, Griffols, Sanoﬁ: Honoraria.OffLabel Disclosure:Rilzabrutinib is an investigational therapy being evaluated in a clinical study for the treatment of patients with immune thrombocytopenia.

01 Jul 2021·ImmunoHorizons

Preclinical Mechanisms of Topical PRN473, a Bruton Tyrosine Kinase Inhibitor, in Immune-Mediated Skin Disease Models

Article

Author: Langrish, Claire L. ; Foulke, Matthew C. ; Bradshaw, J. Michael ; Chen, Wei ; Goldstein, David M. ; By, Kolbot ; Zhu, Jiang ; Loewenstein, Natalie ; Xing, Yan ; Nunn, Philip ; Shu, Jin ; Wadhwa, Jyoti ; Chu, Katherine A. ; Phiasivongsa, Pasit

AbstractThe expression of Bruton tyrosine kinase (BTK) in B cells and innate immune cells provides essential downstream signaling for BCR, Fc receptors, and other innate immune cell pathways. The topical covalent BTK inhibitor PRN473 has shown durable, reversible BTK occupancy with rapid on-rate and slow off-rate binding kinetics and long residence time, resulting in prolonged, localized efficacy with low systemic exposure in vivo. Mechanisms of PRN473 include inhibition of IgE (FcεR)–mediated activation of mast cells and basophils, IgG (FcγR)–mediated activation of monocytes, and neutrophil migration. In vivo, oral PRN473 was efficacious and well tolerated in the treatment of canine pemphigus foliaceus. In this study, we evaluated in vitro selectivity and functionality, in vivo skin Ab inflammatory responses, and systemic pharmacology with topically administered PRN473. Significant dose-dependent inhibition of IgG-mediated passive Arthus reaction in rats was observed with topical PRN473 and was maintained when given 16 h prior to challenge, reinforcing extended activity with once-daily administration. Similarly, topical PRN473 resulted in significant dose-dependent inhibition of the mouse passive cutaneous anaphylaxis IgE-mediated reaction. Multiday treatment with topical PRN473 in rodents resulted in low-to-no systemic accumulation, suggesting that efficacy was mainly due to localized exposure. Reduced skin Ab inflammatory activity was also confirmed with oral PRN473. These preclinical studies provide a strong biologic basis for targeting innate immune cell responses locally in the skin, with rapid onset of action following once-daily topical PRN473 administration and minimal systemic exposure. Dose-dependent inhibition in these preclinical models of immune-mediated skin diseases support future clinical studies.

News (Medical) associated with Principia Biopharma, Inc.

20 Sep 2024

·endpts.com

Sanofi's BTK inhibitor again slows MS progression, but liver enzymes continue to be tricky

Sanofi released new Phase 3 data for its BTK inhibitor tolebrutinib in non-relapsing secondary progressive multiple sclerosis (nrSPMS), showing a 31% improvement in delaying onset of disease progression compared to placebo. But safety issues that have dogged the drug class could complicate the readout. Tolebrutinib is a BTK inhibitor, and it and other related drugs have faced issues with elevated liver enzymes. In the Phase 3 readout, those signals showed up again — 4.1% of patients on tolebrutinib had their liver enzymes jump to three times the normal limit, compared with 1.6% in the placebo group. A smaller group in the trial, called HERCULES, showed even sharper liver enzyme increases: 0.5% of patients saw their liver enzymes spike to 20 times the normal limit, and one of those patients died after needing a liver transplant and suffered post-surgery complications. Every other case resolved without medical intervention, but Sanofi had to implement more rigorous monitoring of patients. Robert Fox, a clinician at the Cleveland Clinic and chair of the HERCULES global steering committee, said that if tolebrutinib is approved, he wouldn’t be surprised if it came with a boxed warning. “Would I be surprised if it’s in a black box? No,” Fox said. “But predicting whether it is or not, that’s not something I can do.” More intensive safety monitoring has lessened the amount of patients whose liver enzymes exceed the 20-fold threshold, but hasn’t eliminated cases entirely, a Sanofi spokesperson told Endpoints News . The spokesperson also said the company is still working through unblinding its safety data and can’t give an exact number of cases after the new protocols were instituted (the patient who died after a liver transplant received the drug beforehand). Sanofi presented the data at the 2024 ECTRIMS conference in Copenhagen. It plans to file with the FDA by the end of 2024. Despite the safety concerns, Fox said the data represented an impressive milestone in MS treatment — the efficacy results were statistically significant, with a p-value of p=0.0026. Fox noted that there isn’t anything on the market to slow secondary progressive MS’ disease progression, and that approved drugs only reduce the frequency of relapse episodes. Tolebrutinib “actually does something where none of the other therapies do anything. So that’s where we are, and so that is the decision that a clinician will have to consider,” Fox said. “If this were to be available for clinical use, how much anti-inflammation does my patient need, and how much slowing [of] that insidious progression does my patient need?” Sanofi acquired tolebrutinib as part of its $3.7 billion acquisition of Principia Biopharma in 2020 and has made it a central part of its new pipeline focus around immunology in addition to amlitelimab (bought from Kymab), lunsekimig (developed from Ablynx’s platform) and rilzabrutinib (also from Principia), among others. But the FDA placed a partial clinical hold on the drug in June 2022 in both MS and myasthenia gravis, an autoimmune disease, after reports of liver injury. While the partial hold remains in effect for other Phase 3 MS studies (it was “modified” to account for the new monitoring protocols, the spokesperson said), Sanofi discontinued development in myasthenia gravis in early 2023. Sanofi released data from two other Phase 3 relapsing MS trials earlier this month comparing tolebrutinib to standard of care, which showed mixed efficacy results. While neither study hit their primary endpoints, a pooled analysis showed they successfully delayed the time to disability. Safety data also presented at ECTRIMS across these two trials were more numerically balanced between the active and standard-of-care arms, but there were still cases of liver enzymes rising 20 times above the normal limit and patient deaths, though the latter were deemed unrelated to treatment. Another Phase 3 in patients with primary progressive MS is expected to read out in 2025. Editor’s note: This story has been updated to correct the p-value from 0.026 to 0.0026, that previously released mixed data came in RMS studies, not nrSPMS, and that patient deaths in these studies were not linked to treatment.

Clinical ResultPhase 3Acquisition

20 Sep 2024

·www.biospace.com

Sanofi’s Tolebrutinib Delays MS Progression in Phase III Study Following Earlier Flops

iStock, JHVEPhoto The positive readout in patients with non-relapsing secondary progressive multiple sclerosis comes on the heels of back-to-back failures in which tolebrutinib was unable to improve relapse rates in patients with relapsing MS. Sanofi on Friday announced that its investigational BTK inhibitor tolebrutinib delayed the onset of disability progression by 31% in patients with non-relapsing secondary progressive multiple sclerosis. The results come from the Phase III HERCULES study, a double-blinded randomized trial that compared daily oral tolebrutinib against placebo in terms of confirmed disease progression at six months, defined using scores in the expanded disability status scale. Friday’s readout from HERCULES also showed that 10% of patients on tolebrutinib experienced confirmed disability improvement, versus around 5% in the placebo arm. This corresponded to an 88% increase in the likelihood of improvement, with a nominal p-value of 0.021, according to Sanofi. In terms of safety, preliminary data from HERCULES pointed to a “slight increase” in adverse events among patients treated with tolebrutinib. Of the patients treated with the BTK inhibitor, 4.1% saw liver enzyme elevations greater than thrice the upper limit of normal, as compared with only 1.6% among placebo comparators. “All but one” case of liver enzyme elevation resolved without medical intervention. One patient in the tolebrutinib arm underwent liver transplantation and died due to complications related to the surgery. This fatality occurred after Sanofi revised its protocol to have more stringent and frequent monitoring, which has since “mitigated such serious liver sequelae.” Tolebrutinib “has demonstrated its ability to delay disability by targeting underlying drivers” of non-relapsing secondary progressive multiple sclerosis (nrSPMS), Houman Ashrafian, Sanofi’s head of R&D, said in a statement. The company will bring these finding to global regulatory authorities, with submissions set to start in the second half of 2024. Jefferies analyst Peter Welford called HERCULES’ readout “promising” in a note to investors. “We view data as positive to enable global filings and approvals given current unmet need for nrSPMS with no effective drugs available.” Importantly, Friday’s findings from HERCULES now makes tolebrutinib a “de-risked $2-3bn opportunity,” Welford wrote. Designed to be administered orally, tolebrutinib is a small molecule inhibitor of the BTK protein, which under healthy circumstances is important for the development and activity of antibody-producing B cells. Tolebrutinib’s mechanism of action allows it to suppress B cells and the disease-driving microglia. Sanofi secured the rights to tolebrutinib in August 2020, when it acquired Principia Biopharma for almost $3.7 billion. The drug candidate has since become a pillar of Sanofi’s multiple sclerosis program , alongside the late-stage antibody frexalimab and the Phase II RIPK1 inhibitor oditrasertib. However, tolebrutinib’s clinical development has not been without its challenges. In June 2022, the FDA slapped a partial clinical hold on the drug and suspended enrollment in its Phase III trials due to drug-induced liver injuries. Earlier this month, Sanofi reported back-to-back Phase III failures for tolebrutinib, which was unable to significantly improve relapse rates in the patients with relapsing forms of MS.

Clinical ResultPhase 3Phase 2AcquisitionADC

04 Sep 2024

·www.prnewswire.com

Global Heparin Market to Reach ~USD 15 Billion by 2030 | DelveInsight

The demand for heparin is mainly increasing due to the growing incidence of cardiovascular diseases, the expanding range of cancer risk factors such as smoking, radiation exposure, unhealthy lifestyles, and other factors, as well as the rising research and development activities by global market players throughout the forecast period from 2024 to 2030. LAS VEGAS, Sept. 4, 2024 /PRNewswire/ -- DelveInsight's Heparin Market Insights report provides the current and forecast market analysis, individual leading heparin companies' market shares, challenges, heparin market drivers, barriers, trends, and key market heparin companies in the market. Key Takeaways from the Heparin Market Report As per DelveInsight estimates, North America is anticipated to dominate the global heparin market during the forecast period. In the application segment of the heparin market, the coronary artery disease category had a significant revenue share in the Heparin market in 2023. Notable heparin companies such as Pfizer Inc., Leo Pharma A/S, Dr. Reddy's Laboratories Ltd., GSK plc., Sanofi, B. Braun Melsungen AG, Aspen Holdings, Fresenius SE & Co. KGaA, Novartis AG, Baxter, and several others, are currently operating in the heparin market. In November 2023, the FDA approved a taurolidine plus heparin (DefenCath®) catheter lock solution to reduce catheter-related bloodstream infections in patients receiving maintenance hemodialysis via a central venous catheter (CVC). In February 2022, Techdow USA Inc. announced the launch of its Heparin Sodium Injection, USP in the US market. In January 2022, the Ohio biotechnology firm Optimvia Pharmaceuticals developed a cost-effective synthetic method to produce large quantities of heparin, used to make common blood thinner, also striking a deal with the synthetic biology firm Ginkgo Bioworks to scale the process up. To read more about the latest highlights related to the heparin market, get a snapshot of the key highlights entailed in the Global Heparin Market Report Heparin Overview Heparin is a widely used anticoagulant medication that helps prevent and treat blood clots. It works by enhancing the activity of antithrombin III, a protein in the blood that inhibits blood clotting factors such as thrombin and factor Xa. Heparin is administered either intravenously or subcutaneously and is commonly used in medical settings such as during surgeries, dialysis, and for patients with certain types of heart disease. Its rapid onset and short duration of action make it particularly useful in acute settings where quick and reversible anticoagulation is needed. Despite its effectiveness, heparin therapy requires careful monitoring due to the risk of bleeding complications. One of the most significant side effects is heparin-induced thrombocytopenia (HIT), a condition where the patient's platelet count drops dramatically, which paradoxically increases the risk of thrombosis. To manage these risks, healthcare providers regularly monitor blood clotting parameters, such as activated partial thromboplastin time (aPTT), to ensure that the patient remains within a therapeutic range. In cases where heparin use is contraindicated or needs to be discontinued, alternative anticoagulants, such as low molecular weight heparins or direct oral anticoagulants, may be considered. Heparin Market Insights In 2023, North America held the largest share of the heparin market compared to other regions. This is attributed to the rising incidence of cardiovascular disorders in the area. Contributing factors include the increasing risk factors related to cardiovascular issues, strong research and development efforts, and a highly promising market for product development and launches, all of which are driving the growth of the heparin market in North America. Additionally, the growing number of heparin product launches is anticipated to drive the heparin market in North America. For instance, in February 2024, B. Braun Medical Inc. introduced its new Heparin Sodium 2,000 units in 0.9% Sodium Chloride Injection, 1,000 mL (2 units/mL), marking the fifth addition to its range of Heparin premixed bags. This launch underscores B. Braun's dedication to enhancing supply security by producing pharmaceuticals in the U.S. at its Irvine, CA facility. Given the substantial patient population in North America, the use of heparin for treatment is expected to boost market demand in the coming years. Consequently, these factors combined are projected to contribute to the growth of the heparin market in North America during the forecast period from 2024 to 2030. To know more about why North America is leading the market growth in the heparin market, get a snapshot of the Heparin Market Outlook Heparin Market Dynamics The heparin market is a critical segment within the global pharmaceutical industry, primarily driven by its essential role in anticoagulant therapy. The market dynamics are influenced by a variety of factors including technological advancements, regulatory changes, and shifts in healthcare practices. One significant driver in the heparin market is the ongoing innovation in drug delivery systems and formulations. Advances such as low molecular weight heparins (LMWHs) have improved the efficacy and safety profiles of heparin therapy, leading to increased adoption. Additionally, the development of more efficient manufacturing processes, such as recombinant heparins, has helped meet the growing demand and reduce dependency on animal sources, which can be susceptible to supply chain disruptions. Regulatory factors also play a crucial role in shaping the heparin market. Regulatory agencies, such as the FDA and the EMA, impose stringent standards on the production and quality of heparin products. These regulations are designed to ensure the safety and efficacy of heparin, which can impact market dynamics through compliance costs and potential market entry barriers for new players. Moreover, market dynamics are influenced by global healthcare trends and economic factors. Rising incidences of cardiovascular diseases and an aging population contribute to the increased demand for heparin. However, economic pressures and healthcare cost containment strategies may impact market growth. Furthermore, competition from alternative anticoagulants and biosimilars can also affect the heparin market by offering patients and healthcare providers additional options. Get a sneak peek at the heparin market dynamics @ Heparin Market Dynamics Analysis Heparin Market Assessment Heparin Market Segmentation Heparin Market Segmentation By Source: Bovine, Porcine, and Others Heparin Market Segmentation By Route of Administration: Subcutaneous and Intravenous Heparin Market Segmentation By Application: Coronary Artery Disease, Atrial Fibrillation, Venous Thromboembolism, Renal Impairment, and Others Heparin Market Segmentation By Geography: North America, Europe, Asia-Pacific, and Rest of World Porter's Five Forces Analysis, Product Profiles, Case Studies, KOL's Views, Analyst's View Which MedTech key players in the heparin market are set to emerge as the trendsetter explore @ Heparin Companies Table of Contents Interested in knowing the heparin market by 2030? Click to get a snapshot of the Heparin Market Trends Related Reports Heparin-induced Thrombocytopenia Market Heparin-induced Thrombocytopenia Market Insight, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key heparin-induced thrombocytopenia companies, including Sandoz, Fresenius Kabi, Hikma Pharm, Veralox Therapeutics, among others. Thrombocytopenia Market Thrombocytopenia Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key thrombocytopenia companies, including Sanofi, Principia Biopharma, Baxalta, Takeda, Argenx, Millennium Pharmaceuticals, Biotest, GC Pharma, Genosco (Subsidiary of Oscotec), Rigel Pharmaceuticals, Kissei Pharmaceutical, Shionogi & Co., Ltd, Amgen, Novartis, Zenyaku Kogyo, among others. Thrombocytopenia Pipeline Thrombocytopenia Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key thrombocytopenia companies, including Takeda, Argenx, Keros Therapeutics, Principia Biopharma, Momenta Pharmaceuticals, Veralox Therapeutics, Novartis Pharmaceuticals, Pfizer, HUTCHMED, Principia Biopharma, Genosco, UCB, among others. Immune Thrombocytopenia Immune Thrombocytopenia Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key immune thrombocytopenia companies, including UCB Biopharma, Sanofi, Principia Biopharma, Argenx, Millennium Pharmaceuticals, Takeda, Biotest, GC Pharma, UCB, HanAll Biopharma, Immunovant, Momenta Pharmaceuticals, Hutchison MediPharma, Cour Pharmaceutical Development, among others. About DelveInsight DelveInsight is a leading Business Consultant, and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP

Drug Approval

100 Deals associated with Principia Biopharma, Inc.

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The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Drug(Targets)	Indications	Global Highest Phase

Rilzabrutinib ( BTK )	Purpura, Thrombocytopenic, Idiopathic More	Phase 3
Atuzabrutinib ( BTK )	Dermatitis, Atopic More	Phase 2
PRN694 ( ITK )	Autoimmune Diseases More	Preclinical
LMP2/7 inhibitor(Principia Biopharma) ( PSMB8 x PSMB9 )	Autoimmune Diseases More	Preclinical
PRN1109 ( FGFRs )	Neoplasms More	Preclinical

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