Updated data expands clinically meaningful results available from FIREFLY-1 pivotal trial

77% of patients who entered the treatment-free observation period following OJEMDA treatment remained off therapy for at least 12 months

The median time to next treatment (TTNT) following initiation of OJEMDA exceeded 3.5 years

BRISBANE, Calif., Nov. 24, 2025 (GLOBE NEWSWIRE) -- Day One Biopharmaceuticals, Inc. (Nasdaq: DAWN) ("Day One" or the "Company"), a biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, today announced three-year results from the OJEMDA pivotal Phase 2 FIREFLY-1 trial in an oral presentation at the 30(th) Annual Meeting & Education Day of the Society for Neuro-Oncology .

New data from the ongoing FIREFLY-1 trial (Arm 1), with an updated median study duration of 40.6 months (data cutoff June 6, 2025), are described below. Primary trial results, including trial eligibility, patient demographics, efficacy and safety have been previously reported (Kilburn, et al. Nature Medicine 2024).

"We are excited by these updated three-year data showing that patients taking tovorafenib were able to spend meaningful time off therapy, with the option to retreat as needed," said Elly Barry, MD, Chief Medical Officer of Day One. "These findings highlight the potential for a treatment approach to help support patients through the long-term course of their disease and further support our view that tovorafenib has the potential to become the second line standard of care in pLGG."

In 76 evaluable patients from Arm 1, 44 (58%) completed 26 or more cycles of treatment (approximately 24 months). Amongst the key primary endpoints, the overall response rate was 53% (40/76), the median duration of response was 19.4 months (95% CI [13.8-27.2]), and the time to response was 5.4 months (range [1.6-17.5]). The pre-specified secondary study endpoint of Progression Free Survival was evaluated by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma. The median was 16.6 (10.9--22.0) months.

Exploratory analyses were also undertaken to further assess the clinical impact of tovorafenib in the same study population. Among these analyses:

   -- The median time-to-next-treatment (defined as the time from the date of 
      the first dose of tovorafenib to the start of the first subsequent 
      anticancer treatment, or date of death) was 42.6 months (95% CI 
      [36.7-NE]). 
   -- 39 patients entered a treatment-free observation period: 
 
          -- 77% (30/39) were treatment-free for a minimum of 12 months. 
 
          -- Median treatment-free interval, measured from the end of 
             tovorafenib primary treatment to the start of the next subsequent 
             anticancer treatment or death, was not reached. 
 
          -- Tumor rebound was minimal in the first 6 months off therapy, with 
             31% of patients experiencing a >=25% increase in tumor size from 
             the last scan prior to the last dose. 
 
          -- Eight patients received retreatment with tovorafenib: 
 
                 -- The median retreatment duration was 9 months (all patients 
                    remained on therapy at the time of data cutoff). 
 
                 -- The median maximum percentage change in tumor reduction was 
                    --38.3%. 

"These three-year data showed that patients were able to maintain disease control during extended periods off therapy, with the option to reinitiate tovorafenib treatment if clinically indicated," said Dr. Cassie Kline, Director of Clinical Research in the Division of Neuro-Oncology at the Children's Hospital of Philadelphia. "This approach has the potential to offer patients and their families meaningful time away from treatment."

In this updated three-year analysis, no new safety signals were identified. Grade 3 or higher adverse events most commonly reported (>= 5% of patients) were decreased growth velocity, anemia, blood creatine phosphokinase increased, maculopapular rash, alanine aminotransferase increased.

Tovorafenib is approved by the U.S. Food and Drug Administration for the treatment of pediatric patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement.

About tovorafenib

Tovorafenib (known as OJEMDA$(TM)$ in the U.S.) is a Type II RAF kinase inhibitor mutant BRAF V600, wild-type BRAF, and wild-type CRAF kinases. Tovorafenib is indicated for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. This indication is approved under accelerated approval based, in part, on response rate and duration of response according to multiple response assessment criteria: Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO LGG) criteria, and Response Assessment for Neuro-Oncology Low-Grade Glioma (RANO LGG) criteria. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Tovorafenib is under evaluation as a therapy for patients aged 6 months to 25 years with pLGG harboring BRAF fusion or rearrangement, or BRAF V600 mutation requiring front-line treatment (Phase III FIREFLY-2/LOGGIC).

Tovorafenib was granted Breakthrough Therapy and Rare Pediatric Disease designations by the FDA for the treatment of patients with pLGG harboring an activating RAF alteration, and it was evaluated by the FDA under priority review. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma and from the European Commission for the treatment of glioma.

For more information, please visit www.ojemda.com.

About Pediatric Low-Grade Glioma

Pediatric low-grade glioma (pLGG) is the most common brain tumor with an estimated US incidence of 1,100 and Europe incidence of 700 children per year who are eligible for front-line systemic therapy.(i) (,) (ii) BRAF is the gene most commonly altered in pLGG, which include two primary types of BRAF alterations -- a BRAF gene fusion and BRAF point mutation. These BRAF alterations account for >50% of pLGG cases worldwide and until now there were no approved treatments for people with pLGG driven by BRAF fusions.(i, iii)

Pediatric low-grade gliomas can be chronic and relentless, with patients suffering profound side effects from both the tumor and the treatment, which may include chemotherapy and radiation. These side effects can impact their life over the long term, and may include muscle weakness, loss of vision, and difficulty speaking. This type of tumor has a high risk of progression, and many children with pLGG require long-term treatment. While most children with pLGG survive their cancer, children who do not achieve a complete resection following surgery may face years of increasingly aggressive treatment.

About FIREFLY-1

FIREFLY-1 is evaluating tovorafenib as once-weekly monotherapy in patients aged 6 months to 25 years with relapsed or progressive pLGG harboring a known activating BRAF alteration. The trial is being conducted in collaboration with the Pediatric Neuro-Oncology Consortium (PNOC). The pivotal and ongoing Phase 2 FIREFLY-1 study evaluated the safety and efficacy of tovorafenib in 137 relapsed or refractory BRAF-altered pLGG patients, who had received at least one line of prior therapy, across two study arms. Arm 1 (n=77) was used for the efficacy analyses and Arm 2 provided safety data for an additional 60 patients, initiated to enable access to tovorafenib once Arm 1 had fully recruited.

At the time of data cutoff on May 10, 2024, the major efficacy outcome measure was overall response rate $(ORR)$ of 53% (40/76), determined by blinded independent central review based on RAPNO-LGG (Response Assessment in Pediatric Neuro-Oncology) criteria. Median duration of response (DOR) was 18 months (12.0, 22.8) and median time to response (TTR) was 5.4 months (range 1.6, 17.5). The most common adverse reactions (>=30%) were rash, hair color changes, fatigue, viral infection, vomiting, headache, hemorrhage, pyrexia, dry skin, constipation, nausea, dermatitis acneiform, and upper respiratory tract infection. Grade 3 or higher adverse reactions (>=5%) were rash, viral infection, and hemorrhage. Additional information about FIREFLY-1 may be found at ClinicalTrials.gov, using Identifier NCT04775485.

About the Pediatric Neuro-Oncology Consortium

The Pediatric Neuro-Oncology Consortium (PNOC) is an international consortium with study sites within the United States, Canada, Europe and Australia dedicated to bringing new therapies to children and young adults with brain tumors.

About Day One Biopharmaceuticals

Day One Biopharmaceuticals believes when it comes to pediatric cancer, we can do better. The Company was founded to address a critical unmet need: the dire lack of therapeutic development in pediatric cancer. Inspired by "The Day One Talk" that physicians have with patients and their families about an initial cancer diagnosis and treatment plan, Day One aims to re-envision cancer drug development and redefine what's possible for all people living with cancer--regardless of age--starting from Day One.

Day One partners with leading clinical oncologists, families, and scientists to identify, acquire, and develop important targeted cancer treatments. The Company's pipeline includes tovorafenib (OJEMDA(TM)) and DAY301.

Day One is based in Brisbane, California. For more information, please visit www.dayonebio.com or find the Company on LinkedIn or X.

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