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Accelerating medicines for both children and adults with cancer

At Day One, our unique approach to cancer drug development represents the start of a new, more inclusive age in oncology therapy. Over the past decade, there has been a revolutionary improvement in scientists’ understanding of the molecular drivers of cancer in children. Simultaneously, we have gained a better understanding of the similarities and differences between adult and childhood malignancies. It’s time to leverage this knowledge to make a meaningful difference in more lives.

Empowering people of all ages to benefit from new cancer treatments

Backed by the latest knowledge and emerging data, Day One is equipped to identify patients across the age spectrum who are likely to benefit from a new treatment based upon their tumor’s biology. In parallel, pediatric oncology clinical trial infrastructure has matured and specialized, enabling greater access to industry-sponsored clinical trials for children with cancer – something historically only available to adult patients. As a result, opportunities now exist to develop new targeted therapies, for both childhood and adult cancers, with equal speed and intensity.

Day One’s pipeline is deeply rooted in cancer biology in order to treat the right patient with the right medicine for the right target. It is also designed for efficiency and speed — enabled by courageous patients and respected investigators. In concert with our collaborators and advisors, we stay at the forefront of the most current clinical and scientific insights to inform our development decisions. Together we are building a robust pipeline of medicines and clinical trials capable of accelerating the advancement of new medicines for people with cancer, whatever their age.

DAY101 (TAK-580) – our lead investigational therapy

DAY101 is an oral and highly  selective investigational pan-RAF inhibitor. The RAS-RAF-MEK-ERK pathway is an essential signaling pathway which regulates key cell functions such as growth and survival. This pathway is one of the most commonly mutated oncogenic pathways in cancer. Genomic alterations in BRAF can lead to constitutive pathway activation, thus driving tumor growth.

DAY101 is currently in clinical development for the treatment of patients with cancer that harbor genetic alterations in RAF. This unique type II RAF-inhibitor has comparably high brain distribution and exposure in comparison to other MAPK pathway inhibitors, thus providing new hope that it may benefit patients with primary brain tumors or brain metastases of solid tumors.

Genomic alterations in BRAF occur in approximately 7-8% of human cancer. The BRAF-V600E point mutation is
the most frequently occurring mutation which drives hyperactivation of the signaling pathway. BRAF mutations occur frequently in patients with a wide range of diseases, including melanoma, papillary thyroid cancer, colorectal cancer, lung cancer, hairy cell leukemia, and craniopharyngioma. BRAF mutations also occur frequently in a number of pediatric cancers, including low and high-grade glioma and Langerhans cell histiocytosis.

Beyond mutations, BRAF wild-type fusions have also been reported in human cancer. These occur when a portion of the BRAF gene becomes fused to a portion of another gene, resulting in constitutive pathway activation and driving oncogenic cell growth. BRAF fusions have been identified in a large percentage of pediatric patients with low-grade gliomas, as well as in a variety of adult cancers, including melanoma, lung cancer, and subtypes of pancreas cancer.

Currently approved medications that target alterations in BRAF are only active in tumors harboring BRAF-V600 mutations, exhibit limited activity in brain tumors, and cannot be used in patients harboring BRAF wild-type fusions. New treatments are needed for patients with tumors dependent on BRAF V600 mutations and BRAF wild-type fusions as well as in patients with brain tumors.

To date, more than 200 patients have been treated with DAY101 as a single agent or in combination with other anti-cancer treatments. Results of a Phase 1 study demonstrated that DAY101 was capable of causing tumor shrinkage in patients with melanoma bearing an activating mutation in BRAF. The most commonly reported treatment-emergent adverse events (any grade) in this population were fatigue, anemia (low red blood cell count), constipation, and rash.

DAY101 is currently being studied in a pediatric Phase 1 clinical trial that is evaluating its safety and clinical activity as a monotherapy in children with recurrent or progressive low-grade astrocytoma associated with BRAF alterations, including BRAF point mutations and the KIAA1549:BRAF wild-type fusion. Information about the open Phase 1 study (PNOC014) can be found here. Day One will be announcing new studies with DAY101 soon.

Expanding our portfolio

At Day One, we are constantly exploring opportunities to initiate drug development programs that address clinical and scientific areas of unmet need – particularly for children with cancer. Our partnership and pipeline activities focus on expanding the potential impact and reach of DAY101 and in-licensing new compounds that fit our all-ages strategy and capabilities.

As our understanding of RAF signaling expands, we are actively exploring combinations of DAY101 with other MAPK pathway‑targeted agents, immune checkpoint inhibitors, and standard‑of‑care agents. By doing so, we will be better able to treat underserved diseases, extend the duration of benefit of therapy, and achieve long‑term durable remissions for more patients – both young and old.

Beyond DAY101, we are also seeking to in-license or acquire promising preclinical and clinical-stage investigational drug candidates that have the potential to change the standard of care across all ages across all of pediatric oncology, but especially:

  • Soft tissue and bone sarcomas
  • High-risk leukemias (AML and ALL)
  • High-risk and relapsed neuroblastoma
  • High-grade glioma
  • Medulloblastoma, AT/RT, ependymoma, and other underserved pediatric brain tumors

If you have a research and development idea you would like to discuss, please contact us at