Company: DAWN
Filing Date: 2025-02-25
Form Type: 10-K
Source: 0000950170-25-026654
Chunk: 78

Company: Day One Biopharmaceuticals, Inc.
Filing Date: 2025-02-25
Form: 10-K
Item: Item 1
Chunk 78
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 prior treatment or who have no satisfactory alternative treatment options. Tovorafenib also received orphan drug designation from the FDA for the treatment of malignant glioma.

Clinical development plan for pLGG

We have completed enrollment of a pivotal Phase 2 FIREFLY-1 trial of tovorafenib in pediatric patients aged six months to 25 years with relapsed or refractory pLGGs harboring an activating BRAF alteration, such as a KIAA1549-BRAF fusion or a BRAF activating mutation, such as V600E. This is an open-label, global registrational, single-arm trial of oral tovorafenib administered once weekly at a dose of 420 mg/m2. Patients are allowed to continue on tovorafenib until radiographic evidence of disease progression by RANO criteria as determined by treating investigator, unacceptable toxicity, patient withdrawal of consent, or death. The first patient was dosed in FIREFLY-1 in May 2021 and we completed enrollment in the registrational arm in May 2022. The FIREFLY-1 trial was also expanded to: (a) include two additional study arms to enable expanded access for eligible patients now that the primary cohort has completed enrollment, and (b) evaluate the preliminary efficacy of tovorafenib in patients aged six months to 25 years with a relapsed or progressive extracranial solid tumor with an activating RAF fusion. This trial generated a dataset that, in combination with the existing safety database, served as the basis for regulatory approval. The primary endpoint was overall response rate, defined as the proportion of patients with best overall confirmed response rate (complete response and partial response based on the RANO criteria), as determined by independent review. Secondary and exploratory endpoints include the overall response rate based on RAPNO and volumetric analyses, event free survival, safety, functional outcomes, and quality of life measures. In April 2024, evaluation of the data from FIREFLY-1 by FDA resulted in accelerated approval of tovorafenib in the United States for the treatment of patients 6 months of age and older with relapsed or refractory pediatric LGG harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. In July 2024, we entered into the Ipsen License Agreement, pursuant to which, we licensed to Ipsen, on an exclusive basis, the right to commercialize tovorafenib in all territories outside the United States and agreed to provide certain research and development