ALX Oncology, a clinical-stage immuno-oncology company developing therapies to block the CD47 checkpoint mechanism, today announced that preclinical data for its SIRPα antibody research program will be presented at the 2019 Keystone Symposia Conference (Keystone), Cancer Immunotherapy in Whistler, British Columbia and the American Association for Cancer Research (AACR) Annual Meeting 2019 in Atlanta, Georgia.
CD47/SIRPα interaction is a key checkpoint mechanism exploited by cancer cells to escape immunological surveillance. While CD47 is widely expressed in human cells, SIRPα, the CD47 inhibitory receptor, is mainly expressed in myeloid cells and neurons. ALX148, a CD47 blocker with an inactive Fc domain, is generally well tolerated and demonstrates anti-cancer activity in combination with trastuzumab and pembrolizumab in patients with anti-HER2 and checkpoint inhibitor resistant/refractory disease (SITC 2018, P335). Another approach to block this interaction is to target SIRPα.
“Targeting the CD47/SIRPα pathway is an exciting new approach that shows promise in clinical trials. By targeting SIRPα, we can investigate the similarities and differences of an orthogonal strategy to inhibit this axis,” said Hong Wan, Ph.D., ALX Oncology’s Chief Scientific Officer. “Our panel of proprietary high affinity monoclonal antibodies provides diverse epitope coverage across the extracellular surface of SIRPα. These antibodies are cross-reactive to human, monkey and rodent SIRPα variants, which enables robust clinical translation. Importantly, these antibodies bind to all human SIRPα variants, a critical attribute for a global patient population.”
ALX Oncology’s SIRPα antibodies enhance the antitumor activity of immune checkpoint inhibitors, with reduction of metastases, eradication of tumors, and acquisition of memory immune response in tumor-bearing mice with intact immune systems. The cellular immune response in syngeneic models shows that these SIRPα antibodies enhance innate and adaptive anti-cancer immunity, providing a rationale for combination with other immunotherapies. In an exploratory toxicology study in monkeys, the selected SIRPα antibodies demonstrate a favorable pharmacokinetic, target occupancy and tolerability profile.
Together, these preclinical data provide a compelling rationale to advance the development of anti-SIRPα therapy for patients with cancer.
Keystone Presentation Information
Title: Discovery of monoclonal antibodies targeting myeloid checkpoint SIRPα to enhance anti-tumor immunity
Session: Poster session 3
Session Date: Wednesday, March 13, 2019
Location: Whistler Conference Centre
Poster Number: 3022
AACR Presentation Information
Title: Antibodies to SIRPα enhance innate and adaptive immune responses to promote anti-tumor activity
Session Category: Immunology
Session Title: Therapeutic Antibodies 1
Session Date and Time: Sunday, March 31, 2019 1:00 PM - 5:00 PM ET
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 23
Abstract Number: 562
About ALX Oncology
ALX Oncology is a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint mechanism, which is exploited by cancer cells to evade the immune system. Our lead candidate, ALX148, is a fusion protein comprised of an engineered high affinity CD47 binding domain of SIRPα linked to an inactive Fc region of human immunoglobulin. ALX148 is designed to maximize the clinical benefit of antibody-based therapies and is in clinical development (NCT03013218) for a broad range of tumor types. www.alxoncology.com
MacDougall Biomedical Communications