On April 9, 2021 Seagen Inc. (Nasdaq: SGEN) reported that preclinical data from its pipeline of novel targeted oncology drugs will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 10-15, 2021 (Press release, Seagen, APR 9, 2021, View Source [SID1234577789]). The oral and poster presentations will highlight several early-stage programs utilizing Seagen’s leading antibody-drug conjugate (ADC) technology as well as its proprietary sugar-engineered antibody (SEA) technology.
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"Our research being presented at AACR (Free AACR Whitepaper) describes intriguing preclinical data for three novel pipeline programs that are in ongoing clinical trials. This includes SEA-TGT, an anti-TIGIT antibody using our SEA technology, and two vedotin-based ADCs, SGN-B6A and SGN-STNV. We believe these three programs represent potential best-in-class or first-in-class targeted therapies for cancer," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "Among the findings, we will show the enhanced therapeutic effect in combining SEA-TGT with a checkpoint inhibitor or a vedotin-based ADC across different tumor models. In addition, we will report for the first time our preclinical data with SGN-STNV, a novel ADC targeting a carbohydrate antigen that may have broad applicability across solid tumors."
Highlights of Seagen Programs Presented at AACR (Free AACR Whitepaper)
SEA-TGT
Preclinical data will be presented for SEA-TGT, a novel investigational nonfucosylated human IgG1 TIGIT antibody, which utilizes Seagen’s proprietary SEA technology that enhances functionality by targeting key immune activating Fc receptors. TIGIT is an inhibitory immune checkpoint that has emerged as a clinically relevant immuno-oncology target. The monotherapy and combinatorial activity of SEA-TGT was assessed and compared to TIGIT monoclonal antibodies (mAbs) with inert, standard, or effector function modified backbones in vivo and in vitro. Key preclinical findings were as follows:
the SEA-TGT backbone was distinct as it increased binding to activating FcγRIIIa with minimal binding to inhibitory FcγRIIb;
the empowered backbone had superior therapeutic properties including enhanced depletion of TIGIT-positive regulatory T-cells and activation of antigen-presenting cells both of which are important in promoting antitumor activity;
SEA-TGT demonstrated enhanced antitumor activity both as a single agent and in combination with anti-PD1 therapy; and,
SEA-TGT produced an enhanced therapeutic effect when combined with an immunogenic tumor cell death-inducing vedotin ADC.
A phase 1 trial evaluating SEA-TGT alone and in combination with anti-PD-1 therapy in patients with advanced solid tumors and select lymphomas is ongoing.
SGN-B6A
Preclinical data will also be presented on SGN-B6A, an investigational ADC targeting integrin beta-6, which is overexpressed in numerous solid tumors and has been demonstrated to be a negative prognostic indicator across a diverse range of cancers, including non-small cell lung cancer (NSCLC). Data demonstrate SGN-B6A is active when dosed weekly in patient-derived xenograft models of NSCLC, representing both squamous and adenocarcinoma histology. A phase 1 trial evaluating monotherapy SGN-B6A in advanced solid tumors is ongoing.
SGN-STNV
SGN-STVN is an investigational ADC with a unique mechanism for targeting a carbohydrate antigen called Sialyl-Thomsen nouveau (STn), which is highly expressed on a variety of solid tumors including non-small cell lung, ovarian and gastric cancers. The preclinical data demonstrate SGN-STNV is highly specific for STn independent of protein identity, which could allow for the targeting of a range of tumor types that express different glycoproteins. In xenograft studies across key tumor types, the specificity and ability to target STn on multiple tumor-associated proteins led to durable tumor regressions. SGN-STNV was well-tolerated in in vivo studies and is being evaluated in an ongoing phase 1 study.
Additional Details of Seagen Presentations at AACR (Free AACR Whitepaper) Annual Meeting 2021
All poster presentations will be available via on-demand view starting on April 10 at 8:30 a.m. Eastern Time. Oral symposium presentations will be available at the beginning of the session where the study is presented.
Abstract Title
Abstract #
Date
Presenter
Oral
Targeting Sialyl-Thomsen nouveau (STn) antigen with the SGN-STNV antibody-drug conjugate is effective in preclinical studies
#50
April 10 in session at 4:00 – 6:00 p.m. ET
A. Schwartz
E-Poster
SEA-TGT is an empowered anti-TIGIT antibody that displays superior combinatorial activity with several therapeutic agents
#1583
April 10
A. Smith
Activity of SGN-B6A in patient-derived xenograft models of non-small cell lung cancer
#914
April 10
R. Lyon
Pharmacokinetics of tucatinib in healthy and hepatically-impaired volunteers
#1371
April 10
A. Topletz-Erickson