duvakitug (SAR447189) / Teva, Sanofi - LARVOL DELTA

Intestinal fibrosis in Crohn's disease : towards new therapeutic options? (PubMed, Rev Med Liege) - "New therapeutic strategies are emerging, including TL1A inhibitors (duvakitug, tulisokibart), an ALK5 inhibitor (AGMB-129), and targeted AGR2 therapies (TH-009). Additionally, mesenchymal stem cells are being investigated in our hospital center in combination with endoscopic balloon dilation, aiming to assess their therapeutic potential. The development of effective anti-fibrotic therapies remains a critical medical need to improve the management of intestinal strictures and reduce the need for invasive procedures in Crohn's disease."

Journal • Review • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • AGR2 • TGFBR1

Teva and Sanofi Present New Positive Phase 2b Study Results at ECCO 2025 Reinforcing Best-in-Class Potential of Duvakitug (Anti-TL1A) in Ulcerative Colitis and Crohn’s Disease (GlobeNewswire) - P2b | N=290 | RELIEVE UCCD (NCT05499130) | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | "In the UC cohort of the RELIEVE UCCD study, 36% (450 mg dose) and 48% (900 mg dose) of patients treated with duvakitug achieved the primary endpoint of clinical remission (mMS) at week 14 compared to 20% treated with placebo; placebo-adjusted rates were 16% (450 mg) and 27% (900 mg) (p=0.050 and 0.003, respectively)....In the CD cohort of the RELIEVE UCCD study, 26% (450 mg) and 48% (900 mg) of patients with CD treated with duvakitug achieved the primary endpoint of endoscopic response (SES-CD) compared to 13% on placebo; placebo-adjusted rates were 13% (450 mg) and 35% (900 mg) at week 14 (p=0.058 and <0.001, respectively)."

P2b data • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Duvakitug (TEV-48574), an anti-TL1a monoclonal antibody, demonstrates efficacy and favourable safety as an induction treatment in adults with moderately to severely active ulcerative colitis: Results from a phase 2b, randomised, double-blind, placebo-controlled, dose-ranging, basket trial (RELIEVE UCCD) (ECCO-IBD 2025) - P2 | "Conclusion Duvakitug demonstrated statistically significant and clinically meaningful treatment responses compared to PBO in patients with UC; it was well tolerated with no emergent safety signals observed. These induction study results support further development of duvakitug as a potential treatment option for patients with moderately to severely active UC."

Clinical • P2b data • Pan tumor • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Duvakitug (TEV-48574), an anti-TL1a monoclonal antibody, demonstrates efficacy and favourable safety as an induction treatment in adults with moderately to severely active Crohn’s disease: results from a phase 2b, randomised, double-blind, placebo-controlled dose-ranging, basket trial (RELIEVE UCCD) (ECCO-IBD 2025) - P2 | "Duvakitug demonstrated statistically significant and clinically meaningful endoscopic response versus PBO with no emergent safety signals observed. These results support further development of duvakitug as a treatment option for patients with moderately to severely active CD."

Clinical • P2b data • Pan tumor • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Teva to Host Conference Call on February 24, 2025 to Discuss New Data Presented for Duvakitug (anti-TL1A) Positive Phase 2b results at the 20th Annual Congress of the European Crohn's and Colitis Organisation (ECCO) (Teva Press Release) - "Teva Pharmaceutical Industries...announced today that it will conduct a conference call and live webcast at 8 am E.T. on Monday, February 24, 2025. During the conference call, Eric Hughes, MD, PhD, Executive Vice President of Global R&D and Chief Medical Officer, and external IBD key opinion leaders (KOLs) will discuss new data presented for duvakitug (anti-TL1A) positive Phase 2b results at the 20th Annual Congress of the European Crohn's and Colitis Organization (ECCO)."

P2b data • Crohn's disease • Ulcerative Colitis

Teva Delivers Second Consecutive Year of Growth; Announces Strong Financial Results in Fourth Quarter and Full Year 2024, Led by Generics Performance and Innovative Portfolio Growth (GlobeNewswire) - "Duvakitug (Anti-TL1A) positive Phase 2B results announced and initiation of Phase 3 program is expected in 2025...AJOVY revenues in our United States segment in the fourth quarter of 2024 were $63 million, an increase of 11% compared to the fourth quarter of 2023...AUSTEDO revenues in our United States segment in the fourth quarter of 2024 increased by 27%, to $518 million, compared to $408 million in the fourth quarter of 2023...UZEDY (risperidone) extended-release injectable suspension revenues in our United States segment in the fourth quarter of 2024 were $43 million...COPAXONE revenues in our United States segment in the fourth quarter of 2024 were $63 million, a decrease of 13% compared to the fourth quarter of 2023, mainly due to market share erosion and competition, partially offset by a reduction in sales allowance."

Commercial • New P3 trial • CNS Disorders • Crohn's disease • Huntington's Disease • Migraine • Multiple Sclerosis • Schizophrenia

Press Release: Duvakitug positive phase 2b results demonstrate best-in-class potential in ulcerative colitis and Crohn’s disease (GlobeNewswire) - P2b | N=290 | RELIEVE UCCD (NCT05499130) | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | "Sanofi and Teva Pharmaceuticals, a US affiliate of Teva Pharmaceutical Industries Ltd., today announced that the RELIEVE UCCD phase 2b study met its primary endpoints in patients with ulcerative colitis (UC) and Crohn’s disease (CD)....In the RELIEVE UCCD study, 36.2% (low dose) and 47.8% (high dose) of patients with UC treated with duvakitug achieved clinical remission compared to 20.45% on placebo, placebo-adjusted rates were 15.7% (low dose) and 27.4% (high dose), at week 14 (p=0.050 and 0.003, respectively). In patients with CD, 26.1% (low dose) and 47.8% (high dose) treated with duvakitug achieved endoscopic response compared to 13.0% on placebo, placebo-adjusted rates were 13.0% (low dose) and 34.8% (high dose), at week 14 (p= 0.058 and <0.001, respectively)....Detailed results are expected to be presented at a scientific forum in 2025."

P2b data • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Duvakitug: “Statistically significant and meaningful responses observed in both UC and CD”; Inflammatory bowel disease (Teva) - Duvakitug (Anti-TL1A) Positive Phase 2b Top Line Results - Conference Call

P2b data • Crohn's disease • Inflammatory Bowel Disease • Ulcerative Colitis

RELIEVE UCCD: A Study to Test the Effect of TEV-48574 in Moderate to Severe Ulcerative Colitis or Crohn's Disease (clinicaltrials.gov) - P2 | N=290 | Completed | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Active, not recruiting ➔ Completed

Trial completion • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study to Evaluate the Long-Term Effect of TEV-48574 in Moderate to Severe Ulcerative Colitis or Crohn's Disease (clinicaltrials.gov) - P2 | N=218 | Active, not recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

CHARACTERIZATION OF TWO NOVEL EXTENDED HALF-LIFE MONOCLONAL ANTIBODY DRUG CANDIDATES TARGETING TL1A FOR THE TREATMENT OF IBD (UEGW 2024) - "Aims & SPY002-091 and SPY002-072 were evaluated in multiple in vitro and ex vivo assays and compared to other anti-TL1A mAbs in clinical development (MK-7240, RG6631, and TEV-48574). We have characterized two anti-TL1A antibodies that exhibit high selectivity and affinity for TL1A, demonstrate effective blockade of the TL1A interaction with DR3, and potently inhibit downstream cellular signaling. With an extended half-life observed in NHP, both SPY002-091 and SPY002-072 demonstrate therapeutic potential for effective and safe treatment of CD and UC with the advantage of infrequent SC dosing. Further preclinical and clinical studies are warranted to demonstrate this potential."

Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • FASLG • TNFA

DISCOVERY AND CHARACTERIZATION OF A NOVEL HIGH-AFFINITY ANTI-TL1A MONOCLONAL ANTIBODY WITH EXTENDED HALF-LIFE FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE (UEGW 2024) - "Select clinical candidate antibodies were further compared to clinical-stage anti-TL1A mAbs PRA023/MK-7240/tulisokibart, RVT-3101/RG6631, and TEV-48574. The clinical candidate antibodies bind with high affinity and specificity to TL1A and demonstrate potent blockade of TL1A-mediated DR3 receptor signaling. In human FcRn knock-in mice and in cynomolgus monkeys, these antibodies show an extended half-life consistent with FDA-approved antibodies using the XtendTM technology. These data demonstrate the therapeutic potential of the clinical candidate antibodies in the treatment of TL1A-mediated diseases such as ulcerative colitis and Crohn’s disease - with the advantage of infrequent subcutaneous dosing."

Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Ulcerative Colitis • CD4 • FASLG • IFNG • TNFA • TNFRSF25

RELIEVE UCCD: A Study to Test the Effect of TEV-48574 in Moderate to Severe Ulcerative Colitis or Crohn's Disease (clinicaltrials.gov) - P2 | N=240 | Active, not recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

TEV-48574, AN ANTI-TL1A ANTIBODY IN DEVELOPMENT FOR USE IN CROHN’S DISEASE AND ULCERATIVE COLITIS, DEMONSTRATES TARGET ENGAGEMENT THROUGH A PROFOUND RAPID AND SUSTAINED REDUCTION IN FREE TL1A LEVELS (UEGW 2024) - "Target engagement was shown by a rapid and sustained TEV-48574-mediated suppression of free TL1A that persisted longer than the drug exposure. Given that TL1A has been implicated in the pathogenesis of immune-mediated and fibrotic diseases, such as IBD1, the data herein support further development of TEV-48574 in patients with ulcerative colitis and Crohn’s disease."

Asthma • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Respiratory Diseases • Ulcerative Colitis • TNFA • TNFRSF25

PHARMACOKINETICS AND TARGET ENGAGEMENT FOLLOWING A SINGLE SUBCUTANEOUS INJECTION OF AN ANTI-TL1A ANTIBODY, TEV-48574, IN CYNOMOLGUS MACAQUES (UEGW 2024) - "TEV-48574 demonstrated an acceptable pharmacokinetic profile with maximum serum concentrations observed within 1 day post-dose of a single sc injection of 5 mg/kg TEV-48574 in 4 male cynomolgus monkeys. Target engagement was shown by a rapid and sustained TEV-48574-mediated suppression of free TL1A in serum, supporting further development of TEV-48574 in patients with ulcerative colitis and Crohn's disease."

PK/PD data • Asthma • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Respiratory Diseases • Ulcerative Colitis • TNFA • TNFRSF25 • TNFRSF6B

A Study to Evaluate the Long-Term Effect of TEV-48574 in Moderate to Severe Ulcerative Colitis or Crohn's Disease (clinicaltrials.gov) - P2 | N=218 | Recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Trial completion date: Aug 2031 ➔ Mar 2031 | Trial primary completion date: Jul 2031 ➔ Dec 2025

Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Teva and Sanofi Announce Accelerated Timeline for Anti-TL1A Phase 2b Program in Patients with Inflammatory Bowel Disease (Teva Press Release) - "Teva Pharmaceuticals...and Sanofi today announced an update to the timing for the anti-TL1A, duvakitug (formerly known as TEV-’574/SAR447189) program investigating the human IgG1-λ2 monoclonal antibody targeting TL1A for moderate-to-severe IBD....Patient enrollment in the RELIEVE UCCD (ulcerative colitis and Crohn’s disease) Phase 2b trial has completed early due to significant acceleration in patient recruitment. As a result, Teva and Sanofi now anticipate having topline results for both UC and CD in Q4 2024, and detailed results will be presented in a scientific forum in 2025. This adjustment replaces the previously planned interim analysis for the second half of 2024, which will not be conducted. Teva and Sanofi are collaborating to co-develop and co-commercialize duvakitug for moderate-to-severe UC and CD patients."

Enrollment closed • P2 data • Crohn's disease • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

FIRST-IN-HUMAN PHARMACOKINETIC AND SAFETY STUDY OF AN ANTI-TL1A ANTIBODY, TEV-48574, IN HEALTHY VOLUNTEERS AND ASTHMA PATIENTS (DDW 2024) - "TEV-48574 was well tolerated at all tested doses in healthy and participants with asthma with dose proportional increases in exposure and minimal accumulation after multiple dosing every two weeks. The data support further development of TEV-48574 in patients with IBD. 1."

Clinical • P1 data • PK/PD data • Asthma • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Ulcerative Colitis • CD40LG • TNFA • TNFSF15

TL1A inhibition for inflammatory bowel disease treatment: From inflammation to fibrosis. (PubMed, Med) - "Investigational drug TEV-48574, potentially exerting dual antifibrotic and anti-inflammatory effects, is undergoing a phase 2 basket study in both ulcerative colitis (UC) and Crohn disease (CD). Results are eagerly awaited, marking advancements in IBD therapeutics. This critical review comprehensively examines the existing literature, illuminating TL1A and the intricate role of DR3 in IBD, emphasizing the evolving therapeutic landscape and ongoing clinical trials, with potential implications for more effective IBD management."

Journal • Review • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

A Study to Evaluate the Long-Term Effect of TEV-48574 in Moderate to Severe Ulcerative Colitis or Crohn's Disease (clinicaltrials.gov) - P2 | N=216 | Recruiting | Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. | Trial completion date: Mar 2026 ➔ Aug 2031 | Trial primary completion date: Feb 2026 ➔ Jul 2031

Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Development and Characterization of SPY002, a Novel Extended Half-life Monoclonal Antibody Drug Candidate Targeting TL1A for the Treatment of IBD (ECCO-IBD 2024) - "Methods SPY002 was evaluated in multiple in vitro and ex vivo assays compared to other clinical anti-TL1A mAbs (PRA023/MK-7240, RVT-3101, and TEV-48574). With an extended half-life in NHP, SPY002 demonstrates therapeutic potential for effective and safe treatment of CD and UC with the advantage of infrequent SC dosing. Further preclinical and clinical studies are warranted to demonstrate this potential."

Crohn's disease • Inflammatory Bowel Disease • Ulcerative Colitis • FASLG • IFNG • TNFA

Phase 2 basket design study evaluating the efficacy and safety of an anti-TL1A antibody (TEV-48574) in moderate to severe ulcerative colitis or Crohn's Disease (RELIEVE UCCD) (ECCO-IBD 2024) - P2 | "Results Conclusion TEV-48574 is a potential novel treatment option for patients with UC and CD that may have dual antifibrotic and anti-inflammatory effects. The phase 2 basket study design offers an efficient approach to advance TEV-45874to confirmatory phase 3 studies."

Clinical • P2 data • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • CD40LG • TNFA • TNFSF15

TEV-48574, an anti-TL1A antibody in development for use in IBD, is safe and well tolerated following 16 weeks of subcutaneous treatment in adults with severe uncontrolled T2-low/non T2 asthma (ECCO-IBD 2024) - P2 | "This is consistent with TL1A being an amplifier of inflammation. Treatment with TEV-48574 may dampen excessive inflammation without inducing a state of immunodeficiency in patients with conditions such as UC or CD, supporting further development in these indications."

Clinical • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • CD40LG • TNFA • TNFSF15

First-in-Human Pharmacokinetic and Safety Study of an Anti-TL1A Antibody, TEV-48574, in Healthy Volunteers and Asthma Patients (ECCO-IBD 2024) - "Clarke A. et al. mAbs .2018;10:664-677."

Clinical • P1 data • PK/PD data • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • CD40LG • TNFA • TNFSF15

Teva Presents New Data Supporting Safety, Tolerability and Target Engagement of Anti-TL1A (TEV-‘574) Antibody at the 2024 ECCO Annual Meeting (Teva Press Release) - "Teva Pharmaceuticals...announced positive safety, tolerability, and pharmacokinetic data for its anti-TL1A (TEV-’574) asset...The data show the rapid and sustained suppression of free TL1A, confirming the target engagement of anti-TL1A (TEV-’574), and show a well-tolerated safety profile in patients with asthma, which support continued clinical investigation for moderate-to-severe inflammatory bowel disease (IBD); this includes ulcerative colitis (UC) and Crohn's disease (CD). These findings will be presented at the 19th Annual Congress of the European Crohn’s and Colitis Organisation (ECCO), which takes place February 21-24, 2024, in Stockholm, Sweden....Also to be presented at ECCO 2024 is the study design of the RELIEVE UCCD Phase 2 trial investigating the efficacy and safety of anti-TL1A (TEV-’574) in patients with moderate-to-severe UC or CD."

Clinical protocol • P1 data • PK/PD data • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis