Actoplus Met XR (pioglitazone/metformin XR) / Takeda - LARVOL DELTA

ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment (clinicaltrials.gov) - P2b | N=6 | Terminated | Sponsor: National Cancer Institute (NCI) | N=13 ➔ 6

Enrollment change • IO biomarker • Head and Neck Cancer • Oncology • Oral Cancer • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CASP3 • CCND1 • CD68 • CDKN1A • PD-1 • PD-L1 • PPARA • PPARG

New Drug Applications approval for five new products in Japan (Takeda Pharmaceutical Company Limited) - Approval from the Health Ministry to manufacture & sell five new drugs, including Nesina (alopliptin), Metact (FDC of Actos with metformin) for diabetes

Regulatory approval - Japan • Diabetes

Orange Book: Approved drug products with therapeutic equivalence evaluations: Newly added patent (FDA) - Newly added patent in Orange Book for Actoplus Met XR.

Patent • Diabetes

ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment (clinicaltrials.gov) - P2b; N=13; Terminated; Sponsor: National Cancer Institute (NCI); N=39 ➔ 13; Active, not recruiting ➔ Terminated; Low accrual combined with expiration of study drug

Clinical • Enrollment change • IO Biomarker • Trial termination

ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment (clinicaltrials.gov) - P2b; N=39; Active, not recruiting; Sponsor: National Cancer Institute (NCI); Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • IO Biomarker

ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment (clinicaltrials.gov) - P2b; N=39; Recruiting; Sponsor: National Cancer Institute (NCI); Trial completion date: Mar 2019 ➔ Aug 2019; Trial primary completion date: Mar 2019 ➔ Aug 2019

Clinical • IO Biomarker • Trial completion date • Trial primary completion date