On March 27, 2019 Seattle Genetics, Inc. (Nasdaq:SGEN) reported data highlights from six presentations showcasing technology advances in the company’s antibody-drug conjugate (ADC) platform and an immuno-oncology program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 being held March 29-April 3, 2019 in Atlanta (Press release, Seattle Genetics, MAR 27, 2019, View Source [SID1234534673]).

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"Our expertise in empowered-antibody innovation drives a substantial, advancing pipeline of clinical and preclinical programs, including both ADCs and immuno-oncology agents," said Dennis Benjamin, Ph.D., Senior Vice President of Research at Seattle Genetics. "For example, the research presented in an oral presentation at AACR (Free AACR Whitepaper) illustrates why we believe SGN-CD228A is well positioned for IND-enabling studies and a phase 1 study is planned in multiple tumor types. The program features a novel ADC targeted to CD228, which is highly expressed in several types of cancer. The ADC employs our proprietary auristatin technology and has shown antitumor activity in vitro and in vivo."

Abstracts can be found at www.aacr.org and include the following:

SGN-CD228A: A novel humanized anti-CD228 antibody-drug conjugate for the treatment of solid tumors (Abstract #2688)
Date: Monday, April 1, 2019
Time: 3:00 p.m. – 5:00 p.m. ET, Oral Presentation at 3:20 p.m. ET, Room B401

The cell-surface protein CD228 is highly expressed in several types of cancer, including melanoma, mesothelioma, non-small cell lung (NSCLC), breast, colorectal and pancreatic cancers. SGN-CD228A is an auristatin-based ADC targeted to CD228. The preliminary data show antitumor activity in preclinical evaluations in melanoma, NSCLC and triple negative breast cancer.

Antibody-drug conjugates of NAMPT inhibitors: Discovery, optimization and preclinical characterization (Abstract #983)
Date: Monday, April 1, 2019
Time: 8:00 a.m. – 12:00 p.m. ET, Poster Session

At the AACR (Free AACR Whitepaper) Annual Meeting 2018, data were presented showing ADCs with a proprietary NAMPT inhibitor payload have a unique mechanism of action and an encouraging therapeutic window. This poster presentation will highlight preclinical results from the optimization of the novel payload and linker strategy, and application to ADCs, which data indicate drive tumor regression in models of Hodgkin lymphoma, non-Hodgkin lymphoma and acute myeloid leukemia (AML). The targeted delivery approach using ADCs demonstrates an improved safety profile relative to previously described unconjugated NAMPT inhibitors.

TIGIT directed human antibody modulates T-regulatory and effector cell function (Abstract #4986)
Date: Wednesday, April 3, 2019
Time: 8:00 a.m. – 12:00 p.m. ET, Poster Session

The immune checkpoint receptor TIGIT negatively regulates the function of adaptive (T cell) and innate (natural killer or NK) cells and blockade of TIGIT signaling may elicit an antitumor immune response. Preclinical data from an antibody program targeting TIGIT demonstrate in vitro activation of T cells and antitumor activity in several syngenic models.

Development of patient-derived acute myeloid leukemia xenograft models (Abstract #1062)
Date: Monday, April 1, 2019
Time: 8:00 a.m. – 12:00 p.m. ET, Poster Session

This poster presentation is focused on successfully establishing a collection of AML xenograft models that more accurately reflect the antigen expression and molecular genetics of AML patients. These models will enable a more precise assessment of therapeutic candidates in preclinical testing.

Functional cell surface proteomics of acute myeloid leukemia enables predictive modeling of antibody-drug conjugate cytotoxicity (Abstract #4546)
Date: Wednesday, April 3, 2019
Time: 8:00 a.m. – 12:00 p.m. ET, Poster Session

This poster profiles the cell surface landscape of more than 100 primary hematologic samples comprising leukemic blasts from patients treated in the Beat AML research consortium along with normal bone marrow cells from healthy donors. Based on cell surface proteomics, a number of highly expressed antigens were identified and targeted ADCs were evaluated on a panel of AML cell lines. CD317 was determined as a novel target for AML.

Tisotumab vedotin induces anti-tumor activity through MMAE-mediated, Fc-mediated, and Fab-mediated effector functions in vitro (Abstract #221)
Date: Sunday, March 31, 2019
Time: 1:00 p.m. – 5:00 p.m. ET, Poster Session

Tisotumab vedotin is an investigational ADC designed to target Tissue Factor (TF) antigen on TF-expressing cell surfaces and deliver the cell-killing agent monomethyl auristatin E (MMAE) directly inside TF-expressing cells. The Tissue Factor antigen target is overexpressed in the vast majority of patients with cervical cancer and in many other solid tumors, including ovarian, lung, pancreatic, colorectal and head and neck. This poster presentation evaluates tisotumab vedotin’s antitumor activity through several mechanisms, including immunogenic cell death, bystander cytotoxicity, and antibody-dependent cellular phagocytosis in vitro.