tesevatinib (KD019) / Sanofi - LARVOL DELTA

CARACTERIZACIÓN CLÍNICA Y EPIDEMIOLÓGICA DE LA ENFERMEDAD RENAL POLIQUÍSTICA EN PACIENTES ATENDIDOS EN UN CENTRO DE REFERENCIA DE CUARTO NIVEL DEL CARIBE COLOMBIANO DURANTE EL PERIODO 2008-2022 (ISN-WCN 2024) - "Los pacientes que presentan una progresión rápida de esta patología se benefician del antagonista del receptor V2 de la vasopresina Tolvaptan, único aprobado hasta el momento por la FDA (34)(35). Se encuentran en investigación moléculas como lixivaptan, venglustat, bardoxolona, tesevatinib, RGLS4326 (oligonucleótido inhibidor de microARN miR-17), GLPG2737 (corrector regulador de conductancia transmembrana de fibrosis quística), los cuales han venido demostrando efectos benéficos potenciales (36)(37)(38)(39). Otros medicamentos como everolimus ha evitado la progresión del volumen renal, pero no evitó la progresión de la enfermedad (40)... La ERP es una patología sistémica de relevancia importante debido al gran impacto que puede producir al deteriorar la salud de la persona comprometida, puede cursar desde estados asintomáticos a casos donde la función renal esta severamente deteriorada y por..."

Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Oncology • MIR17 • PKD1 • PRKD1

Tesevatinib (KD019) vs Placebo for ADPKD: Results of a Ph2b Trial (NKF-SCM 2023) - "Higher incidence of study-drug related TEAEs was reported for subjects in the KD019 group (n=30, 78.9%) compared with placebo (n=24, 60.0%).Conclusion KD019 50 mg QD did not demonstrate efficacy in slowing cystic kidney growth or in slowing eGFR decline over 24 mos in ADPKD pts at risk of rapid progression. Similarly, subgroup analysis by Mayo class did not suggest a role for KD019 in any ADPKD subgroup."

Clinical • P2b data • Autosomal Dominant Polycystic Kidney Disease • Polycystic Kidney Disease

Emerging interventions to slow Autosomal Dominant Polycystic Kidney Disease progression: A systematic review (ISN-WCN 2023) - "Data effects of prescribed water intake, vitamin D supplementation, Tesevatinib and ketogenic diets were limited to narrative synthesis. Conclusions Metformin and Bosutinib are promising on preserving eGFR and slowing TKV, while Pravastatin and ketogenic diet may be good adjunct therapies. Further Randomised control trials are however needed."

Review • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Pain • Polycystic Kidney Disease • Renal Disease

Pan-ErbB inhibition protects from SARS-CoV-2 replication, inflammation, and lung injury (ACS-Fall 2022) - "Lapatinib and additional pan-ErbB inhibitors (ibrutinib, sapitinib, afatinib and tesevatinib) suppressed replication of SARS-CoV-2 and other unrelated viruses in human cell lines with a high barrier to resistance. These findings reveal regulation of viral infection, inflammation, and lung injury via ErbBs in part via a mechanism that involves S1-NRP1 binding. Moreover, they propose approved candidates to counteract these effects with implications for pandemic coronaviruses and unrelated viruses."

Acute Lung Injury • Fibrosis • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Oncology • Respiratory Diseases • EGFR • ERBB4 • HER-2 • NRP1

Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD (clinicaltrials.gov) - P2 | N=80 | Completed | Sponsor: Kadmon Corporation, LLC | Active, not recruiting ➔ Completed

Trial completion • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

In vivo efficacy of tesevatinib in patient-derived xenograft glioblastoma models may be limited by tissue binding and compensatory signaling. (PubMed, Mol Cancer Ther) - "Overall, tesevatinib efficacy in EGFR amplified PDX GBM models is robust in vitro but relatively modest in vivo, despite a high brain-to-plasma ratio. This discrepancy may be explained by drug-tissue binding and compensatory signaling."

Journal • Preclinical • Brain Cancer • Glioblastoma • Immunology • Oncology • Solid Tumor • ABCB1

Tesevatinib: Expiry of patents related to composition-of-matter, method of use, formulations and method of making in Australia, Canada, EU, Japan and US for oncology beyond 2023, beyond 2025 and beyond 2026 (Kadmon) - Annual Report 2020: Expiry of patents related to method of use in US, Canada, China, Eurasia, EU, Japan and Taiwan for polycystic kidney disease beyond 2031

Patent • Oncology

Biocept to Present Study Results from Target Selector Testing in the Cerebrospinal Fluid of Patients with Lung Cancer at the IASLC Liquid Biopsy Meeting (StockHouse) - "This prospective study evaluated results from Biocept's combined circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) liquid biopsy testing compared to conventional cytology examination, the current standard-of-care, for confirming the diagnosis of leptomeningeal metastases in patients with EGFR-mutated NSCLC undergoing treatment with Tesevatinib, an experimental EGFR tyrosine kinase inhibitor (NCT02616393)."

Diagnostic • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Study of Tesevatinib Monotherapy in Patients With Recurrent Glioblastoma (clinicaltrials.gov) - P2; N=40; Completed; Sponsor: Kadmon Corporation, LLC; Active, not recruiting ➔ Completed

Clinical • Monotherapy • Trial completion • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • EGFR

[VIRTUAL] Clinical anti-lymphoma effect of T cells expressing an anti-CD19 chimeric antigen receptor in synthetic biology optimizing system. (ASCO 2020) - "KD-019 CAR T cells express an anti-CD19 chimeric antigen receptor in synthetic biology optimizing system. this innovative KD-019 product can offer significant clinical benefit for NHL patients at the low dose without fever and neurotoxicity. Research Funding: Nanjing Kaedi Biotech, INC"

Clinical • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pain

Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer (clinicaltrials.gov) - P1b/2a; N=17; Terminated; Sponsor: Kadmon Corporation, LLC; N=80 ➔ 17; Active, not recruiting ➔ Terminated; Sponsor closed the study in order to review data from other ongoing tesevatinib oncology studies, and to determine feasibility of continuing this study

Enrollment change • Trial termination • Biosimilar • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

Tesevatinib in Subjects With ADPKD (clinicaltrials.gov) - P2; N=100; Recruiting; Sponsor: Kadmon Corporation, LLC; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar • Renal Disease

Tesevatinib: Anticipated initiation of P2 trial in EGFR-mutant NSCLC with CNS metastases in Q2 2017 (Kadmon) - Corporate Presentation: Anticipated data from P2 trial in EGFR-mutant NSCLC with CNS metastases in Q4 2018

New P2 trial • P2 data • Non Small Cell Lung Cancer • Oncology

Kadmon initiates phase 2 clinical trial evaluating tesevatinib in glioblastoma (Kadmon Press Release) - P2, N=40; NCT02844439; "Kadmon Holdings...today announced that the first patient has been dosed in a Phase 2 clinical trial of tesevatinib...for the treatment of recurrent glioblastoma...study examines tesevatinib monotherapy administered at 300 mg once daily in up to 40 patients in the United States."

Enrollment open • Oncology

Kadmon: Corporate Presentation (Kadmon) - Anticipated presentation of data from first 13 patients in P2 trial (NCT02616393) in NSCLC with activating EGFR mutations and brain metastases or leptomeningeal disease at WCLC (December 4-7, 2016); Anticipated additional top-line data from P2 trial in NSCLC in Q1 2017

Anticipated P2 data • Non Small Cell Lung Cancer • Oncology

Kadmon: IASLC 2016 (Kadmon) - "Tesevatinib rapidly improved CNS metastases and related clinical symptoms and tumor volumes in NSCLC patients with activating EGFR mutations who failed standard EGFR TKI therapy"; "11 of the 13 patients showed no CNS progression on tesevatinib"

P2 data • Non Small Cell Lung Cancer • Oncology

Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD (clinicaltrials.gov) - P2; N=80; Active, not recruiting; Sponsor: Kadmon Corporation, LLC; Recruiting ➔ Active, not recruiting; Trial completion date: Aug 2020 ➔ Jan 2022; Trial primary completion date: Aug 2020 ➔ Jan 2022

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • MRI

Tesevatinib: Expiry of patents related to composition-of-matter and method of use in Australia, Canada, Europe, Japan and US for oncology in 2026 (Kadmon) - Annual Report 2019: Expiry of patents related to method of use in Canada, China, Eurasia, Europe, Taiwan and US for polycystic kidney disease in 2031

Patent

Study of Tesevatinib Monotherapy in Patients With Recurrent Glioblastoma (clinicaltrials.gov) - P2; N=40; Active, not recruiting; Sponsor: Kadmon Corporation, LLC; Trial primary completion date: Jan 2020 ➔ Mar 2020

Trial primary completion date • EGFR

Study of Tesevatinib in Subjects With Non-Small Cell Lung Cancer, EGFR Activating Mutation, Prior Treatment With a Tyrosine Kinase Inhibitor, and Brain Metastases or Leptomeningeal Metastases (clinicaltrials.gov) - P2; N=36; Completed; Sponsor: Kadmon Corporation, LLC; Active, not recruiting ➔ Completed; N=60 ➔ 36

Clinical • Enrollment change • Trial completion

Study of Tesevatinib in Subjects With Non-Small Cell Lung Cancer, EGFR Activating Mutation, Prior Treatment With a Tyrosine Kinase Inhibitor, and Brain Metastases or Leptomeningeal Metastases (clinicaltrials.gov) - P2; N=36; Completed; Sponsor: Kadmon Corporation, LLC; Trial completion date: Aug 2018 ➔ Jan 2019; Trial primary completion date: Aug 2018 ➔ Jan 2019

Clinical • Trial completion date • Trial primary completion date

Autosomal dominant polycystic kidney disease: updated perspectives. (PubMed, Ther Clin Risk Manag) - "In our review, we also shed some lights on what is beyond Tolvaptan as there are other medications in the pipeline and many medications have been or are currently being studied in clinical trials such as Tesevatinib, Metformin and Pravastatin, with the goal of slowing the rate of progression of ADPKD by reducing the increase in total kidney volume or maintaining eGFR. Here, we review updates in the perspectives and management of ADPKD."

Journal • Review

A Safety, Pharmacokinetic, Single Ascending Dose Study of Tesevatinib in Pediatric Subjects With Autosomal Recessive Polycystic Kidney Disease (ARPKD) (clinicaltrials.gov) - P1; N=10; Completed; Sponsor: Kadmon Corporation, LLC; Recruiting ➔ Completed; N=18 ➔ 10; Trial completion date: Dec 2019 ➔ Sep 2019; Trial primary completion date: Dec 2019 ➔ Sep 2019

Clinical • Enrollment change • Trial completion • Trial completion date • Trial primary completion date

Safety and Efficacy Results from the SILK (Safety in Larger Kidneys) Cohort of KD019-101: A Phase 1b/2a Trial of the Tyrosine Kinase Inhibitor Tesevatinib for Patients with ADPKD (KIDNEY WEEK 2019) - "An ongoing randomized placebo controlled trial is actively recruiting. Funding Commercial Support"

Clinical • P1/2 data

Study of Tesevatinib Monotherapy in Patients With Recurrent Glioblastoma (clinicaltrials.gov) - P2; N=40; Active, not recruiting; Sponsor: Kadmon Corporation, LLC; Trial completion date: Sep 2019 ➔ Dec 2019

Trial completion date