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Neoplasms

Immune System Diseases

Hemic and Lymphatic Diseases

Small molecule drug

Bispecific T-cell Engager (BiTE)

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

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Most frequently developed targets

Disease Domain	Count

Neoplasms	2
Immune System Diseases	2
Hemic and Lymphatic Diseases	2
Endocrinology and Metabolic Disease	1
Nervous System Diseases	1

Top 5 Drug Type	Count

Small molecule drug	2
Bispecific T-cell Engager (BiTE)	1

Top 5 Target	Count

TRPA1(Transient receptor potential cation channel subfamily A member 1)	1
CD3 x CD38	1
HPK1(Mitogen-activated protein kinase kinase kinase kinase 1)	1

Heavy chain (Hc) heterodimers represent a majority of bispecific antibodies (bsAbs) under clinical development. Although recent technologies achieve high levels of Hc heterodimerization (HD), traces of homodimer contaminants are often present, and as a consequence robust purification techniques for generating highly pure heterodimers in a single step are needed. Here, we describe two different purification methods that exploit differences in Protein A (PA) or Protein G (PG) avidity between homo- and heterodimers. Differential elution between species was enabled by removing PA or PG binding in one of the Hcs of the bsAb. The PA method allowed the avidity purification of heterodimers based on the VH3 subclass, which naturally binds PA and interferes with separation, by using a combination of IgG3 Fc and a single amino acid change in VH3, N82aS. The PG method relied on a combination of three mutations that completely disrupts PG binding, M428G/N434A in IgG1 Fc and K213V in IgG1 CH1. Both methods achieved a high level of heterodimer purity as single-step techniques without Hc HD (93-98%). Since PA and PG have overlapping binding sites with the neonatal Fc receptor (FcRn), we investigated the effects of our engineering both in vitro and in vivo. Mild to moderate differences in FcRn binding and Fc thermal stability were observed, but these did not significantly change the serum half-lives of engineered control antibodies and heterodimers. The methods are conceptually compatible with various Hc HD platforms such as BEAT® (Bispecific Engagement by Antibodies based on the T cell receptor), in which the PA method has already been successfully implemented.

01 Aug 2019·Journal of Allergy and Clinical ImmunologyQ1 · MEDICINE

GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis

Q1 · MEDICINE

Article

Author: Grossman, Fred ; Xu, Hui ; Gudi, Girish ; Ca, Vinu ; Fang, Hui ; Wen, Huei-Chi ; Govas, Panayiota ; Back, Jonathan ; Maari, Catherine ; Peng, Xiangyu ; Estrada, Yeriel D ; Reddy, Venkateshwar ; Zhou, Lisa ; Salhi, Yacine ; Zhang, Ning ; Bissonnette, Robert ; Pavel, Ana B ; Wolff, Gerhard ; Guttman-Yassky, Emma

BACKGROUNDGBR 830 is a humanized mAb against OX40, a costimulatory receptor on activated T cells. OX40 inhibition might have a therapeutic role in T cell-mediated diseases, including atopic dermatitis (AD).OBJECTIVEThis exploratory phase 2a study investigated the safety, efficacy, and tissue effects of GBR 830 in patients with AD.METHODSPatients with moderate-to-severe AD (affected body surface area, ≥10%; Eczema Area and Severity Index score, ≥12; and inadequate response to topical treatments) were randomized 3:1 to 10 mg/kg intravenous GBR 830 or placebo on day 1 (baseline) and day 29. Biopsy specimens were collected (n = 40) at days 1, 29, and 71. Primary end points included treatment-emergent adverse events (TEAEs) and changes from baseline in biomarkers (epidermal hyperplasia/cytokines) at days 29 and 71.RESULTSGBR 830 was well tolerated, with equal TEAE distribution (GBR 830, 63.0% [29/46]; placebo, 63.0% [10/16]). One serious TEAE in the GBR 830 group was deemed unrelated to study drug. At day 71, the proportion of intent-to-treat subjects achieving 50% or greater improvement in Eczema Area and Severity Index score was greater with GBR 830 (76.9% [20/26]) versus placebo (37.5% [3/8]). GBR 830 induced significant progressive reductions in T_H1 (IFN-γ/CXCL10), T_H2 (IL-31/CCL11/CCL17), and T_H17/T_H22 (IL-23p19/IL-8/S100A12) mRNA expression in lesional skin. Significant progressive reductions until day 71 in the drug group were seen in OX40⁺ T cells and OX40L⁺ dendritic cells (P < .001). Hyperplasia measures (thickness/keratin 16/Ki67) showed greater reductions with GBR 830 (P < .001).CONCLUSIONSTwo doses of GBR 830 administered 4 weeks apart were well tolerated and induced significant progressive tissue and clinical changes until day 71 (42 days after the last dose), highlighting the potential of OX40 targeting in patients with AD.

100 Deals associated with Ichnos Sciences SA

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100 Translational Medicine associated with Ichnos Sciences SA

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Pipeline

Pipeline Snapshot as of 23 Dec 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

IND Application

1

Phase 1 Clinical

Phase 2 Clinical

1

2

Other

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

GRC-17536 ( TRPA1 )	Diabetic peripheral neuropathy More	Phase 2
GBR-1342 ( CD3 x CD38 )	Relapse multiple myeloma More	Phase 1
GRC-54276 ( HPK1 )	Advanced Malignant Solid Neoplasm More	IND Application
GBR-1302 ( CD3 x HER2 )	Metastatic human epidermal growth factor 2 positive carcinoma of breast More	Discontinued
Telazorlimab ( OX40 )	Dermatitis, Atopic More	Pending