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Therapy Areas: Cardiovascular
Forbius Demonstrates Target Engagement in Phase 1 Immuno-Oncology Clinical Trial with AVID200, First-in-Class TGF-beta 1 and 3 Inhibitor
1 October 2019 - - US-based Forbius, a clinical-stage protein engineering company that develops biotherapeutics to treat fibrosis and cancer, has reported results from its non-clinical GLP toxicology program with first-in-class selective TGF-beta inhibitor AVID200 and evidence of TGF-beta target engagement in patients treated with this novel immuno-oncology agent at the European Society of Medical Oncology 2019 Annual Congress in Barcelona, the company said.
The presentation detailed for the first time that AVID200 administered at doses of ≥1 mg/kg sequestered its target TGF-beta in patient blood over the entire dosing period.
Key highlights of the ESMO presentation include that AVID200 selectively neutralises TGF-beta 1 and 3 with pM potency in vitro, and increases T-cell-mediated cytotoxicity as well as immune checkpoint inhibitor efficacy in syngeneic mouse tumor models
According to the company, AVID200 was well tolerated in 1- and 6-month GLP toxicology studies in non-human primates; AVID200 in patient blood sequestered peripheral TGF-beta over the entire dosing period; and a Phase 1a AVID200 monotherapy dose-escalation clinical trial is currently enrolling solid tumor patients (AVID200-03; NCT03834662).
TGF-beta 1 and 3 are the main oncogenic TGF-beta isoforms expressed by many solid tumors.
They are believed to play a major role in T-cell suppression, fibrosis, and resistance to anti-PD-(L)1 therapies such as nivolumab (Opdivo) and pembrolizumab (Keytruda) (Chakravarthy et al., Nature Comm., 2018; Tauriello et al., Nature, 2018; Mariathasan et al., Nature, 2018).
AVID200 is an isoform-selective and highly potent inhibitor of TGF-beta 1 and 3 undergoing Phase 1 clinical testing in solid tumors and fibrotic diseases.
TGF-beta 1 and 3 are the principal disease-driving isoforms, while TGF-beta 2 is responsible for normal cardiac function and hematopoiesis.
AVID200's selectivity for TGF-beta 1 and 3 was designed to achieve optimal efficacy while circumventing cardiac and other safety issues that have limited the applicability of older-generation, non-selective TGF-beta inhibitors.
Therefore, AVID200 is positioned to be an effective and well-tolerated therapeutic in a variety of clinical settings, including in combination with anti-PD-(L)1 therapy.
AVID200-03 (NCT03834662) is an open label, multicenter, dose-escalation study to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor effects of AVID200 in patients with advanced or metastatic solid tumor malignancies.
The presentation detailed for the first time that AVID200 administered at doses of ≥1 mg/kg sequestered its target TGF-beta in patient blood over the entire dosing period.
Key highlights of the ESMO presentation include that AVID200 selectively neutralises TGF-beta 1 and 3 with pM potency in vitro, and increases T-cell-mediated cytotoxicity as well as immune checkpoint inhibitor efficacy in syngeneic mouse tumor models
According to the company, AVID200 was well tolerated in 1- and 6-month GLP toxicology studies in non-human primates; AVID200 in patient blood sequestered peripheral TGF-beta over the entire dosing period; and a Phase 1a AVID200 monotherapy dose-escalation clinical trial is currently enrolling solid tumor patients (AVID200-03; NCT03834662).
TGF-beta 1 and 3 are the main oncogenic TGF-beta isoforms expressed by many solid tumors.
They are believed to play a major role in T-cell suppression, fibrosis, and resistance to anti-PD-(L)1 therapies such as nivolumab (Opdivo) and pembrolizumab (Keytruda) (Chakravarthy et al., Nature Comm., 2018; Tauriello et al., Nature, 2018; Mariathasan et al., Nature, 2018).
AVID200 is an isoform-selective and highly potent inhibitor of TGF-beta 1 and 3 undergoing Phase 1 clinical testing in solid tumors and fibrotic diseases.
TGF-beta 1 and 3 are the principal disease-driving isoforms, while TGF-beta 2 is responsible for normal cardiac function and hematopoiesis.
AVID200's selectivity for TGF-beta 1 and 3 was designed to achieve optimal efficacy while circumventing cardiac and other safety issues that have limited the applicability of older-generation, non-selective TGF-beta inhibitors.
Therefore, AVID200 is positioned to be an effective and well-tolerated therapeutic in a variety of clinical settings, including in combination with anti-PD-(L)1 therapy.
AVID200-03 (NCT03834662) is an open label, multicenter, dose-escalation study to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor effects of AVID200 in patients with advanced or metastatic solid tumor malignancies.
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