MEDI6469 / AstraZeneca, Providence Cancer Center, AgonOx - LARVOL DELTA

Anti-OX40 Antibody in Head and Neck Cancer Patients (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: Providence Health & Services | Active, not recruiting ➔ Completed

Trial completion • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Anti-OX40 Antibody in Head and Neck Cancer Patients (clinicaltrials.gov) - P1 | N=17 | Active, not recruiting | Sponsor: Providence Health & Services

Metastases • Trial completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Anti-OX40 Antibody in Head and Neck Cancer Patients (clinicaltrials.gov) - P1 | N=17 | Active, not recruiting | Sponsor: Providence Health & Services | Trial completion date: Oct 2022 ➔ Oct 2023 | Trial primary completion date: Apr 2022 ➔ Apr 2023

Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Anti-OX40 Antibody (MEDI6469) in Patients With Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=4 | Terminated | Sponsor: Providence Health & Services | PI left the institution shortly afterwards and the study will not be re-activated. Only 4 patients were enrolled.

Combination therapy • IO biomarker • Trial termination • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Oncology • Solid Tumor • CD38 • CD4 • CD8

Neoadjuvant anti-OX40 (MEDI6469) prior to surgery in head and neck squamous cell carcinoma. (ASCO 2018) - P1; "Preoperative MEDI6469 administration is safe and resulted in increased activation and proliferation of T cells within the tumor, peaking two weeks following infusion. Immunologic changes are associated with MHC I-mediated antigen processing machinery."

Clinical • IO biomarker • PD(L)-1 Biomarker • Head and Neck Cancer

Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells. (PubMed, Nat Commun) - P1 | "These data provide evidence that anti-OX40 prior to surgery is safe and can increase activation and proliferation of CD4+ and CD8+ T cells in blood and tumor. Our work suggests that increases in the tumor-reactive CD103+ CD39+ CD8+ TIL could serve as a potential biomarker of anti-OX40 clinical activity."

Clinical • IO biomarker • Journal • Head and Neck Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

OX40 agonists for cancer treatment: a patent review. (PubMed, Expert Opin Ther Pat) - "United States was the leader in generating patents, followed by China and England. Major pharmaceutical companies have at least one anti-OX40 agonist, MEDI6469 and MEDI-0562 (AstraZeneca), PF-04518600 (Pfizer), GSK3174998 (GlaxoSmithKline), BMS-986178 (Bristol-Myers Squibb) and MOXR0916 (Roche), which represent 68% of clinical trials conducted with OX40 agonists."

Journal • Immune Modulation • Inflammation • Oncology

Medimmune establishes three-year partnership with the National Cancer Institute to advance oncology research (Medimmune Press Release) - "MedImmune...announced today that it has entered into two umbrella Cooperative Research and Development Agreements (CRADAs) with the National Cancer Institute (NCI)...that are focused on immunotherapy and tumor targeted therapies for cancer....the two immunotherapy projects will evaluate: Combination activity of four investigational compounds in genetically engineered mouse models; MEDI4736 (PD-L1), MEDI0680 (PD-1), tremelimumab (CTLA-4) and MEDI6469 (mOX40)...Cancer vaccine combinations with three investigational agents in preclinical models; MEDI4736, tremelimumab and MEDI6469 (mOX40)."

Anticipated preclinical • Licensing / partnership • Oncology

AstraZeneca: Annual Report 2015 (AstraZeneca) - Discontinuation in solid tumors due to strategic reason; Discontinuation of MEDI6469 + rituximab in solid tumors due to strategic reason; Discontinuation of MEDI6469 + tremelimumab in solid tumors due to strategic reason

Discontinued • Biosimilar • Gastrointestinal Cancer • Non Small Cell Lung Cancer • Oncology

AstraZeneca: Q3 2014 Results (AstraZeneca) - Anticipated completion of enrollment of P1/2 trial for advanced malignancies in Q2 2016

Anticipated enrollment status • Oncology

AstraZeneca: Q1 2015 Results (AstraZeneca) - Anticipated enrollment completion in P1/2 trial (NCT02205333) in advanced malignancies in Q3 2016; Anticipated top-line data from P1/2 trial (NCT02205333) in advanced malignancies in Q1 2017

Anticipated enrollment status • Anticipated P1/2 data • Oncology

Anti-OX40 Antibody (MEDI6469) in Patients With Metastatic Colorectal Cancer (clinicaltrials.gov) - P1; N=44; Recruiting; Sponsor: Providence Health & Services

New P1 trial • Biosimilar • Colorectal Cancer • Oncology

AstraZeneca: Q3 2014 Results (AstraZeneca) - Anticipated completion of P1/2 trial for advanced malignancies in Q2 2016

Anticipated trial completion date • Oncology

A novel TNFR2 antibody induces T cell co-stimulation and promotes durable anti-tumor immunity (AAI 2019) - "...MM-401 has agonistic activity; upon incubation of MM-401 with human CD4+ and CD8+ T cells, we observed upregulation of activation markers and cytokine production comparable to MEDI6469 (anti-OX40). We also observed that MM-401 promotes antibody-dependent cellular cytotoxicity (ADCC) in an NK cell-mediated in vitro assay and a reduction in the number of Treg cells in human ovarian cancer ascites. These data suggest that MM-401 could also promote anti-tumor immunity by mediating ADCC, as well as by direct co-stimulation of T cell responses, and justifies the continued development of MM-401 as a novel cancer immunotherapy"

IO Biomarker

A novel human TNFR2 antibody (MM-401) modulates T cell responses in anti-cancer immunity (AACR 2019) - "Upon incubation of MM-401 with CD4+ and CD8+ T cells from healthy human blood, we observed upregulation of activation markers and cytokine production comparable to utomilumab (anti-4-1BB), MEDI6469 (anti-OX40), and TRX518 (anti-GITR). Currently, we are evaluating MM-401 in patient derived xenograft (PDX) models in humanized mice generated using NSG-SGM3 mice with cord blood CD34+ hematopoietic stem cells. These results justify the continued development of MM-401 as a modulator of anti-tumor immunity for the treatment of cancer."

IO Biomarker

Stereotactic Body Radiation and Monoclonal Antibody to OX40 (MEDI6469) in Breast Cancer Patients With Metastatic Lesions (clinicaltrials.gov) - P1/2; N=14; Completed; Sponsor: Providence Health & Services; Active, not recruiting ➔ Completed; Trial completion date: Jan 2019 ➔ Aug 2018

Clinical • Combination therapy • Trial completion • Trial completion date