Principia Biopharma

Pipeline (1)

• TolebrutinibSmall moleculeBTK InhibitorLed by Sanofi
  • Multiple sclerosisApprovedApproved

Deals & partnerships

• TolebrutinibLed by Sanofi

• Sep 28, 2020AcquisitionSanofi completes ~$3.68 billion acquisition of Principia Biopharma, taking full control of tolebrutinibSanofi completed its tender offer for Principia Biopharma at $100 per share (~$3.68B), acquiring the originator of tolebrutinib (PRN2246/SAR442168) plus rilzabrutinib and topical PRN473. Sanofi had licensed tolebrutinib from Principia in 2017 and moved to full ownership as the compound entered Phase 3 in multiple sclerosis. Agreement announced 2020-08-17; tender expired 2020-09-25; completion announced 2020-09-28.Tolebrutinibsource ↗

Catalysts · 0 upcoming · 5 reported

Recently reported

• 2025-12-15missed

  TolebrutinibforMultiple sclerosisTopline data

  PERSEUS Phase 3 missed its primary endpoint in primary progressive MS: tolebrutinib did not delay time to 6-month composite confirmed disability progression vs placebo (n=767, 2:1); Sanofi will not pursue regulatory registration in PPMS.

  source ↗

• 2024-09-20met

  TolebrutinibforMultiple sclerosisFull results

  HERCULES full results at ECTRIMS 2024: 31% delay in time to onset of 6-month confirmed disability progression vs placebo (HR 0.69; 95% CI 0.55-0.88; p=0.0026); confirmed disability improvement nearly doubled (10% vs 5%; HR 1.88; nominal p=0.021).

  source ↗

• 2024-09-02mixed

  TolebrutinibforMultiple sclerosisTopline data

  GEMINI 2 Phase 3 missed its primary endpoint: tolebrutinib did not reduce annualized relapse rate vs teriflunomide in relapsing MS; disability benefit appeared only in the pooled GEMINI 1+2 key secondary (29% delay in 6-month CDW, nominal p=0.023).

  source ↗

• 2024-09-02mixed

  TolebrutinibforMultiple sclerosisTopline data

  GEMINI 1 Phase 3 missed its primary endpoint: tolebrutinib did not reduce annualized relapse rate vs teriflunomide in relapsing MS; pooled GEMINI 1+2 key secondary showed a 29% delay in 6-month confirmed disability worsening (HR 0.71; 95% CI 0.53-0.95; nominal p=0.023).

  source ↗

• 2024-09-02met

  TolebrutinibforMultiple sclerosisTopline data

  HERCULES Phase 3 met its primary endpoint: tolebrutinib delayed time to onset of 6-month confirmed disability progression vs placebo in non-relapsing secondary progressive MS - the first Phase 3 win in this population.

  source ↗

Recent activity

• Jun 23, 2026Phase changeTolebrutinib·Multiple sclerosisApprovedEuropean Commission approved Cenrifki (tolebrutinib) for secondary progressive MS without relapses in the last two years - the compound's first major-market marketing authorization and the first disability-targeting medicine approved for this population. NOT FDA-approved: the US nrSPMS NDA received a CRL 2025-12-24 and no resubmission has been announced as of 2026-08-14.source ↗
• Dec 15, 2025ReadoutTolebrutinib·Multiple sclerosismissedPERSEUS Phase 3 missed its primary endpoint in primary progressive MS: tolebrutinib did not delay time to 6-month composite confirmed disability progression vs placebo (n=767, 2:1); Sanofi will not pursue regulatory registration in PPMS.source ↗
• Mar 25, 2025Phase changeTolebrutinib·Multiple sclerosisFiled (NDA)US NDA for non-relapsing secondary progressive MS accepted for Priority Review with target action date 2025-09-28 (later extended to 2025-12-28 after a major amendment, then resolved as a complete response letter on 2025-12-24). EU submission was also under review, yielding a CHMP positive opinion 2026-04-24. Dated to the FDA acceptance announcement; the underlying submission was earlier but its exact date was not separately announced.source ↗
• Sep 20, 2024ReadoutTolebrutinib·Multiple sclerosismetHERCULES full results at ECTRIMS 2024: 31% delay in time to onset of 6-month confirmed disability progression vs placebo (HR 0.69; 95% CI 0.55-0.88; p=0.0026); confirmed disability improvement nearly doubled (10% vs 5%; HR 1.88; nominal p=0.021).source ↗
• Sep 2, 2024ReadoutTolebrutinib·Multiple sclerosismixedGEMINI 2 Phase 3 missed its primary endpoint: tolebrutinib did not reduce annualized relapse rate vs teriflunomide in relapsing MS; disability benefit appeared only in the pooled GEMINI 1+2 key secondary (29% delay in 6-month CDW, nominal p=0.023).source ↗
• Sep 2, 2024ReadoutTolebrutinib·Multiple sclerosismixedGEMINI 1 Phase 3 missed its primary endpoint: tolebrutinib did not reduce annualized relapse rate vs teriflunomide in relapsing MS; pooled GEMINI 1+2 key secondary showed a 29% delay in 6-month confirmed disability worsening (HR 0.71; 95% CI 0.53-0.95; nominal p=0.023).source ↗
• Sep 2, 2024ReadoutTolebrutinib·Multiple sclerosismetHERCULES Phase 3 met its primary endpoint: tolebrutinib delayed time to onset of 6-month confirmed disability progression vs placebo in non-relapsing secondary progressive MS - the first Phase 3 win in this population.source ↗
• Jun 11, 2020Phase changeTolebrutinib·Multiple sclerosisPhase 3GEMINI 2 (NCT04410991) started 2020-06-11, the first of four Phase 3 studies; GEMINI 1 followed 2020-06-30, PERSEUS 2020-08-13, and HERCULES 2020-09-24. Date is the earliest actual Phase 3 start on ClinicalTrials.gov.source ↗
• Mar 29, 2019Phase changeTolebrutinib·Multiple sclerosisPhase 2Phase 2b dose-finding study NCT03889639 (DRI15928) started in relapsing MS: 130 participants, tolebrutinib 5/15/30/60 mg once daily. Sanofi ran the study under its 2017 license/collaboration with originator Principia Biopharma (acquired outright in September 2020).source ↗

Competitive landscape

Other companies developing against Principia Biopharma's targets or indications.

• AB Science1 compoundMultiple sclerosis