AO-176 / Arch Oncology - LARVOL DELTA

KEYNOTE-C49: AO-176 in Multiple Solid Tumor Malignancies (clinicaltrials.gov) - P1/2 | N=57 | Completed | Sponsor: Arch Oncology | Active, not recruiting ➔ Completed | N=183 ➔ 57 | Trial primary completion date: Mar 2023 ➔ Nov 2022

Enrollment change • Trial completion • Trial primary completion date • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

Study of AO-176 as Monotherapy and in Combination With Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=10 | Completed | Sponsor: Arch Oncology | Active, not recruiting ➔ Completed | N=157 ➔ 10 | Trial completion date: Mar 2024 ➔ Nov 2022

Combination therapy • Enrollment change • Monotherapy • Trial completion • Trial completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Unleashing the Potential of CD47-Mediated Therapy: New Agonist Triggers Programmed Cancer Cell Death in Hematological Malignancies (EACR 2023) - "Compared to the previously published anti-CD47 antibodies Magrolimab and AO-176, CO-1 is superior both in terms of PCCD of hematological malignant cells and had higher treatment efficacy in the BCP-ALL xenograft model at low doses. Furthermore, CO-1 displayed a high safety profile in B cells derived from healthy human donors.ConclusionCompared with other anti-CD47 antibodies, our results demonstrate that CO-1 is superior both in vitro and in vivo in terms of its unique mechanisms of action and its enhanced efficacy. By inducing PCCD combined with selective phagocytosis of cancer cells, CO-1 may provide a new therapeutic strategy for improving the outcome of patients with hematological malignancies."

Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • ANXA5 • CD47 • SIRPA

[VIRTUAL] 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 (ASH 2020) - P1/2 | "In vivo treatment with AO-176 in combination with these agents is in progress. AO-176 is being evaluated in phase 1 clinical trials for the treatment of patients with solid tumors (NCT03834948) and multiple myeloma (NCT04445701)."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • Solid Tumor

CD47 antibody, AO-176 demonstrates potent anti-tumor activity in pre-clinical solid tumor xenografts as a single agent and in combination with multiple classes of therapeutics (SITC 2021) - P1/2 | "AO-176 treatment in solid tumor xenograft models resulted in potent anti-tumor activity as a monotherapy (40–58% TGI) and in combination with paclitaxel in an ovarian model (99% TGI), cisplatin in an ovarian model (84% TGI), cisplatin in a gastric model (76% TGI), and an anti-VEGFR-2 in a gastric model (86% TGI). AO-176 also elicits potent anti-tumor activity in xenograft and syngeneic models as a single agent and in combination with chemotherapies, monoclonal antibodies and T-cell checkpoint inhibitors. AO-176 is currently in clinical trials as a single agent and in combination in patients with select solid cancers (NCT03834948) and in multiple myeloma (NCT04445701)."

Combination therapy • IO biomarker • Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • CD47 • SIRPA

[VIRTUAL] AO-176, a highly differentiated clinical stage anti-CD47 antibody, preferentially binds tumor versus normal cell CD47 when complexed to β1 integrin (SITC 2020) - P1/2 | "Conclusions The context dependent binding of AO-176 to CD47, when complexed to β1 integrin, is unique among CD47 axis targeting agents and together with its direct killing mechanism of action offers a potentially better safety profile and opportunity for a therapeutic advantage. AO-176 is currently being evaluated in Phase 1 clinical trials for the treatment of patients with select solid tumors (NCT03834948) and multiple myeloma (NCT04445701)."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor

AO-176, a Differentiated Clinical-Stage Anti-CD47 Antibody, Demonstrates Potent Anti-Tumor Activity across Multiple Preclinical Models of B Cell Neoplasms (ASH 2021) - P1/2 | "We then compared the anti-tumor activity of AO-176 against the second generation proteosome inhibitor carfilzomib in a myeloma xenograft model. In summary, the robust preclinical data in DLBCL and MM warrants further development of AO-176 for treatment of hematological malignancies. AO-176 is being evaluated in phase 1/2 clinical trials for the treatment of patients with solid tumors (NCT03834948) and with MM (NCT04445701)."

Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Acute Lymphoblastic Leukemia

[VIRTUAL] 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 (ASH 2020) - P1/2 | "When combined with the proteasome inhibitor bortezomib, AO-176 treatment at both 10 mg/kg and 25 mg/kg resulted in profound RPMI-8226 xenograft growth inhibition, near-total CRs (19/20 mice), and extended survival at both doses. Combining AO-176 and the anti-CD38 antibody daratumumab or immunomodulatory drugs (lenalidomide/pomalidomide) both produced significant enhancement of anti-tumor activity in xenograft models...In summary, the pre-clinical potent single agent activity and enhanced activity when combined with standard of care anti-MM agents, warrants further development of AO-176 in MM treatment. AO-176 is being evaluated in phase 1 clinical trials for the treatment of patients with solid tumors (NCT03834948) and with MM (NCT04445701)."

Combination therapy • IO biomarker • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology • Solid Tumor • CD38

Highly Differentiated Anti-CD47 Antibody, AO-176, Potently Inhibits Hematologic Malignancies Alone and in Combination (ASH 2019) - P1; "In combination with agents targeting CD20 (rituximab) or CD38 (daratumumab), AO-176 mediates enhanced phagocytosis of lymphoma and multiple myeloma cell lines, respectively...When combined with bortezomib, AO-176 was able to elicit complete tumor regression (100% CR in 10/10 animals treated with either 10 or 25 mg/kg AO-176 + 1 mg/kg bortezomib) with no detectable tumor out to 100 days at study termination...With AO-176’s highly differentiated MOA and binding characteristics, it may have the potential to improve upon the safety and efficacy profiles relative to other agents in this class. AO-176 is currently being evaluated in a Phase 1 clinical trial (NCT03834948) for the treatment of patients with select solid tumors."

AO-176, a highly differentiated humanized anti-CD47 antibody, exhibits single-agent and combination antitumor efficacy with chemotherapy and targeted antibodies (AACR-NCI-EORTC 2019) - P1; "When combined with tumor-targeted antibodies (i.e. cetuximab against head and neck and colorectal cancer cell lines, or the checkpoint inhibitor avelumab against ovarian cancer cell lines), AO-176 significantly enhanced phagocytosis of the tumor cells in vitro. In combination with the chemotherapeutics paclitaxel and cisplatin, AO-176 also potentiated direct tumor killing of gastric cancer cells in vitro...With a highly differentiated mechanism of action and binding profile, AO-176 may have the potential to improve upon the safety and efficacy profiles relative to other agents in this class. AO-176 is currently being evaluated in a Phase 1 clinical trial (NCT03834948) for the treatment of patients with select solid tumors."

Clinical • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Hematological Malignancies • Lung Cancer • Lymphoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Thoracic Cancer

[VIRTUAL] AO-176, a highly differentiated clinical stage anti-CD47 antibody, is efficacious in pre-clinical models of lymphoma (AACR 2021) - P1/2 | "Using a variety of cell based and in vivo models we show that AO-176 demonstrates increased binding to lymphoma cells at an acidic versus physiologic pH and that this binding and blocking of the do not eat me signal leads to enhanced phagocytosis of lymphoma cells either alone or in combination with rituximab. We also demonstrate that AO-176 is a potent tumor growth inhibitor in lymphoma xenograft models and appears to induce immune infiltrates as well as inflammatory cytokines.Taken together, these data show that AO-176 has strong therapeutic potential in lymphoma. AO-176 is currently being evaluated in clinical trials of select solid tumors (NCT03834948) and multiple myeloma (NCT04445701)."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor • CD47

KEYNOTE-C49: AO-176 in Multiple Solid Tumor Malignancies (clinicaltrials.gov) - P1/2 | N=183 | Active, not recruiting | Sponsor: Arch Oncology | Recruiting ➔ Active, not recruiting

Enrollment closed • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

Study of AO-176 as Monotherapy and in Combination With Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=157 | Active, not recruiting | Sponsor: Arch Oncology | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Monotherapy • Hematological Malignancies • Multiple Myeloma • Oncology

A Novel Affinity Engineered Anti-CD47 Antibody With Improved Therapeutic Index That Preserves Erythrocytes and Normal Immune Cells. (PubMed, Front Oncol) - "Of particular interest, STI-6643 preserved T cell functionality in vitro and showed significantly lower immune cell depletion in vivo in contrast to three previously published competitor reference anti-CD47 clones Hu5F9, AO-176 and 13H3. Finally, STI-6643 displayed comparable anti-tumor activity to the high-affinity reference clone Hu5F9 in a RAJI-Fluc xenograft tumor model as monotherapy or in combination with anti-CD20 (rituximab) or anti-CD38 (daratumumab) mAbs. These data suggest that STI-6643 possesses the characteristics of an effective therapeutic candidate given its potent anti-tumor activity and low toxicity profile."

IO biomarker • Journal • Oncology • CD47 • SIRPA

Study of AO-176 as Monotherapy and in Combination With Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=157 | Recruiting | Sponsor: Arch Oncology | N=102 ➔ 157

Combination therapy • Enrollment change • Monotherapy • Hematological Malignancies • Multiple Myeloma • Oncology

Study of AO-176 as Monotherapy and in Combination With Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=102 | Recruiting | Sponsor: Arch Oncology | Trial completion date: Mar 2023 ➔ Mar 2024 | Trial primary completion date: Mar 2023 ➔ Mar 2024

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

[VIRTUAL] A first-in-human study of AO-176, a highly differentiated anti-CD47 antibody, in patients with advanced solid tumors. (ASCO 2021) - P1/2 | "Dexamethasone tapering and shortening of the infusion duration to 2 hrs was successful in all pts after cycle 1 . AO-176 is a well-tolerated, differentiated anti-CD47 therapeutic . Durable anti-tumor activity was observed . Evaluations of AO-176 in combination with paclitaxel in pts with select solid tumors (NCT03834948) and as a single-agent in pts with multiple myeloma (NCT04445701) are ongoing."

Clinical • P1 data • Anemia • Cardiovascular • Endometrial Cancer • Fatigue • Gastric Cancer • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • Thrombocytopenia

Arch Oncology Receives U.S. FDA Orphan Drug Designation for AO-176, a Next-Generation Anti-CD47 IgG2 Antibody, for the Treatment of Multiple Myeloma (GlobeNewswire) - "Arch Oncology, Inc...announced that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to AO-176 on January 3rd, 2022, for the treatment of relapsed/refractory multiple myeloma (r/r MM)."

Orphan drug • Hematological Malignancies • Multiple Myeloma • Oncology

[VIRTUAL] AO-176, a highly differentiated clinical stage anti-CD47 antibody, preferentially binds tumor versus normal cell CD47 when complexed to β1 integrin (SITC 2020) - P1/2 | "Conclusions The context dependent binding of AO-176 to CD47, when complexed to β1 integrin, is unique among CD47 axis targeting agents and together with its direct killing mechanism of action offers a potentially better safety profile and opportunity for a therapeutic advantage. AO-176 is currently being evaluated in Phase 1 clinical trials for the treatment of patients with select solid tumors (NCT03834948) and multiple myeloma (NCT04445701)."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor

Arch Oncology Announces First Patient Dosed in Phase 1/2 Clinical Trial of Anti-CD47 Antibody AO-176 in Multiple Myeloma (GlobeNewswire) - "Paul Richardson, M.D...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.'"

Media quote

AO-176 in Multiple Solid Tumor Malignancies (clinicaltrials.gov) - P1/2; N=183; Recruiting; Sponsor: Arch Oncology; N=132 ➔ 183; Trial completion date: Jul 2021 ➔ Mar 2023; Trial primary completion date: Apr 2021 ➔ Mar 2023

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

[VIRTUAL] The differentiated CD47 monoclonal antibody AO-176 exhibits significant in vivo activity against xenograft models of pediatric acute lymphoblastic leukemia (ALL) (AACR 2021) - "Despite being tested in highly immune-deficient mice, the naked antibody AO-176 exhibited significant single-agent in vivo anti-leukemic activity against pediatric T-lineage ALL PDXs. The significant decrease in spleen infiltration elicited by AO-176 in 3/4 PDXs suggests on-target activity consistent with the known mechanism of action of CD47 targeting agents."

Late-breaking abstract • Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Cancer antigen 19-9 • CD47 • PTPRC

Arch Oncology Secures $105 Million Series C Financing (GlobeNewswire) - “Arch Oncology…announced that it has closed a $105 million Series C financing…‘This financing enables the clinical progress of our differentiated anti-CD47 product candidate AO-176, currently in Phase 1/2 clinical trials for solid tumors, both as a monotherapy and in combination with paclitaxel, and multiple myeloma. Looking forward, we plan to expand the AO-176 clinical program to include a combination trial with pembrolizumab (KEYTRUDA®) in solid tumors, and a combination trial with standard therapies in multiple myeloma.”

Financing • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor

Arch Oncology Presents New Preclinical T-ALL Data on Highly-differentiated Anti-CD47 Antibody AO-176 at AACR 2021 (GlobeNewswire) - “Arch Oncology, Inc…announced the presentation of new preclinical data on AO-176 in pediatric acute lymphoblastic leukemia (T-ALL) during a late-breaking poster presentation at the AACR Annual Meeting 2021…‘AO-176 demonstrated significant single-agent in vivo anti-leukemic activity in pediatric T-lineage ALL PDX models. Our antibody delayed disease progression and decreased human leukemia infiltration of murine spleens to increase overall survival in mice inoculated with T-ALL cells, suggesting that targeting CD47 in T-ALL may be a promising therapeutic approach’….‘AO-176 exhibited impressive single-agent in vivo activity for a monoclonal antibody against highly-aggressive experimental models of pediatric T-cell acute lymphoblastic leukemia. Given its novel mechanisms of action and single-agent activity, there is great interest in next testing AO-176 in combination with standard-of-care drugs against..."'

Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Oncology

Arch Oncology Announces Two New Preclinical Data Presentations on Highly Differentiated Anti-CD47 Antibody AO-176 at AACR 2021 (GlobeNewswire) - "Arch Oncology...announced the presentation of new preclinical data on AO-176 at the American Association for Cancer Research (AACR) Annual Meeting 2021...'In lymphoma, we are presenting AO-176’s potent in vivo activity in a lymphoma xenograft, where induction of inflammatory cytokines and immune infiltrates is also observed. Enhanced binding and phagocytosis of lymphoma cells at acidic pH will also be shown in vitro by AO-176 or in combination with rituximab...we look forward to sharing new nonclinical data in pediatric T-ALL during a late-breaking poster presentation at AACR next month'."

Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • Oncology