On December 7, 2020 Arch Oncology, Inc., a clinical-stage immuno-oncology company focused on the discovery and development of anti-CD47 antibody therapies, reported that the first patient has been dosed in a new Phase 1/2 clinical trial for AO-176 in relapsed/refractory multiple myeloma (Press release, Arch Oncology, DEC 7, 2020, View Source;utm_medium=rss&utm_campaign=arch-oncology-announces-first-patient-dosed-in-phase-1-2-clinical-trial-of-anti-cd47-antibody-ao-176-in-multiple-myeloma [SID1234572317]). AO-176 is an anti-CD47 antibody with a potential best-in-class profile that works by blocking the "don’t eat me" signal and also by directly killing tumor cells, with preferential binding to tumor versus normal cells. In preclinical myeloma models involving large tumors, AO-176 has demonstrated promising activity as a single agent as well as in combination with standard approved therapies used to treat this disease.

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"We are excited to begin dosing patients in our second clinical trial for AO-176," said Julie Hambleton, M.D., Interim President and Chief Executive Officer of Arch Oncology. "This is an important milestone for AO-176 and for patients as this is the first dedicated trial of an anti-CD47 antibody exclusively in patients with multiple myeloma. In our first clinical trial of AO-176, we saw encouraging anti-tumor activity as a single agent in patients with solid tumors and we are excited to evaluate our therapy for patients with multiple myeloma. With this second clinical trial initiated, we are making progress advancing AO-176 for both solid tumors and hematologic malignancies as we aim to deliver new cancer treatments to broader groups of patients."

Paul Richardson, M.D., Director of Clinical Research at the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute and Co-Principal Investigator for this clinical trial, commented, "Research shows AO-176 has a highly-differentiated mechanism among this promising new class of anti-CD47 agents. We look forward to evaluating AO-176 as a monotherapy and in combination with standard therapies for patients with relapsed and refractory multiple myeloma. Patients who have progressed despite multiple lines of prior treatment urgently need new treatment options, and we are eager to assess the safety and preliminary efficacy profile of this exciting novel agent."

This open-label, multi-center, dose-escalation Phase 1/2 trial is evaluating the safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary efficacy of AO-176 in patients with relapsed/refractory multiple myeloma. Up to 100 patients whose disease has progressed following at least three prior lines of treatment will be enrolled. In Phase 1, patients enrolled in up to four dose-escalation cohorts will receive AO-176 monotherapy. Next, patients will receive AO-176 in combination with dexamethasone and bortezomib. Then, in Phase 2, patients will receive a recommended dose of AO-176 in combination with dexamethasone and bortezomib to evaluate the safety and preliminary efficacy of this combination.

Parameswaran Hari, MD, MRCP, MS, Chief of the Division of Hematology and Oncology in the Department of Medicine and Professor at Medical College of Wisconsin and Principal Investigator for this clinical trial, added, "We are pleased to dose the first patient in this new multiple myeloma clinical trial. As we treat patients with multiple myeloma, an incurable disease for many patients, we look forward to evaluating AO-176 as a potential new treatment option for patients living with this disease. Given the mechanism and profile of AO-176, we envision additional future combinations with AO-176 to evaluate as future treatments for patients."

Recent Preclinical Data Presentations on AO-176 in Multiple Myeloma

Event: ASH (Free ASH Whitepaper) Annual Meeting & Exposition 2020

Date: December 5, 2020 7:00 am – 3:30 pm PT
Abstract Title: Pre-clinical Combination of AO-176, a Highly Differentiated Clinical Stage CD47 Antibody, with Either Azacitidine or Venetoclax Significantly Enhances DAMP Induction and Phagocytosis of Acute Myeloid Leukemia

Date: December 6, 2020 7:00 am – 3:30 pm PT
Abstract Title: AO-176, a Highly Differentiated Clinical Stage Anti-CD47 Antibody, Exerts Potent Anti-Tumor Activity in Preclinical Models of Multiple Myeloma as a Single Agent and in Combination With Approved Therapeutics

About AO-176

AO-176 is a humanized anti-CD47 IgG2 antibody with a potential best-in-class profile. AO-176 is highly differentiated, with the potential to improve upon the safety and efficacy profile relative to other agents in this class of innate checkpoint inhibitors. AO-176 works by blocking the "don’t eat me" signal, the standard mechanism of anti-CD47 antibodies. Beyond blocking this signal, AO-176 has additional mechanisms, including directly killing tumor cells and inducing DAMPs (Damage Associated Molecular Patterns), resulting in Immunogenic Cell Death. Importantly, AO-176 binds preferentially to tumor cells, instead of to normal cells, and binds even more potently to tumors in their acidic microenvironment (low pH). Publications and presentations on AO-176 can be found at View Source

AO-176 is being evaluated in Phase 1/2 clinical trials for the treatment of patients with select solid tumors and multiple myeloma, both as monotherapy and in combination with standard therapies. In a Phase 1 trial in solid tumors, AO-176 demonstrated encouraging safety and evidence of anti-tumor activity when administered as a single agent. Additional information about these trials may be found at www.clinicaltrials.gov using the trial identification number NCT03834948 (solid tumors) or NCT04445701 (multiple myeloma).