Delving into the Latest Updates on AbbVie LLC with Synapse

Overview

Tags

Endocrinology and Metabolic Disease

Other Diseases

Nervous System 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

Nervous System Diseases	3
Endocrinology and Metabolic Disease	3
Neoplasms	2
Infectious Diseases	2
Immune System Diseases	2
Hemic and Lymphatic Diseases	2

Top 5 Drug Type	Count

Small molecule drug	3

Top 5 Target	Count

Bcl-2(Apoptosis regulator Bcl-2)	1
JAK1 x JAK2 x JAK3 x TYK2	1
DDC x DRDs	1

Rovalpituzumab tesirine (Rova-T) offers a targeted therapy for ~85% of SCLC patients whose tumors express DLL3, but clinical dosing is limited due to off-target toxicities. We hypothesized that a sub-efficacious dose of Rova-T combined with anti-PD1, which alone shows a clinical benefit to ~15% of SCLC patients, might elicit a novel mechanism of action and extend clinical utility. Using a pre-clinical murine SCLC tumor model that expresses Dll3 and has an intact murine immune system, we found that sub-efficacious doses of Rova-T with anti-PD1 resulted in enhanced anti-tumor activity, compared to either monotherapy. Multiplex immunohistochemistry (IHC) showed CD4 and CD8 T-cells primarily in normal tissue immediately adjacent to the tumor. Combination treatment, but not anti-PD1 alone, increased Ki67+/CD8 T-cells and Granzyme B+/CD8 in tumors by flow cytometry and IHC. Antibody depletion of T-cell populations showed CD8+ T-cells are required for in vivo anti-tumor efficacy. Whole transcriptome analysis as well as flow cytometry and IHC showed that Rova-T activates dendritic cells and increases Ccl5, Il-12, and Icam more than anti-PD1 alone. Increased tumor expression of PDL1 and MHC1 following Rova-T treatment also supports combination with anti-PD1. Mice previously treated with Rova-T + anti-PD1 withstood tumor re-challenge, demonstrating sustained anti-tumor immunity. Collectively our pre-clinical data support clinical combination of sub-efficacious Rova-T with anti-PD1 to extend the benefit of immune checkpoint inhibitors to more SCLC patients.

100 Deals associated with AbbVie LLC

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100 Translational Medicine associated with AbbVie LLC

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Pipeline

Pipeline Snapshot as of 22 Nov 2024

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

Approved

3

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Upadacitinib hemihydrate ( JAK1 x JAK2 x JAK3 x TYK2 )	Crohn Disease More	Approved
Venetoclax ( Bcl-2 )	Small Lymphocytic Lymphoma More	Approved
Carbidopa/Levodopa ( DDC x DRDs )	Parkinson Disease More	Approved