On March 6, 2023 Day One Biopharmaceuticals (Nasdaq: DAWN), a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, reported its fourth quarter and full year 2022 financial results and highlighted recent corporate achievements (Press release, Day One, MAR 6, 2023, View Source [SID1234628204]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Day One made tremendous progress in 2022 on our mission of bringing novel targeted therapies to children with brain cancer and people of all ages with life-threatening diseases," said Jeremy Bender, Ph.D., chief executive officer of Day One. "With positive topline results from the FIREFLY-1 study and commercial launch planning well underway, we believe we are on track to submit our first New Drug Application in the first half of this year. Given the significant unmet need for new therapies in children with relapsed or progressive pediatric low-grade gliomas, our team is laser focused on executing on our mission."

Program Highlights

•
In March 2023, Day One dosed the first patient in the pivotal Phase 3 FIREFLY-2/LOGGIC clinical trial evaluating tovorafenib as a frontline therapy for patients newly diagnosed with pLGG.
o
The study is a randomized, monotherapy, open-label trial aiming to enroll approximately 400 patients aged 6 months to 25 years across approximately 100 sites globally, including in the United States, Europe and Asia.
o
The primary endpoint will be the overall response rate (ORR) based upon Response Assessment for Neuro-Oncology (RANO) criteria as reported by Blinded Independent Central Review.
o
Secondary endpoints will include safety, progression-free survival, overall survival, duration of response, functional outcomes and quality of life measures.

•
In January 2023, Day One announced positive topline results from the ongoing, open-label, pivotal Phase 2 FIREFLY-1 trial evaluating tovorafenib (DAY101) as a monotherapy in relapsed or progressive pLGG. The primary endpoint of the FIREFLY-1 trial is ORR by RANO criteria as assessed by Blinded Independent Central Review. Topline results as of September 28, 2022 include:
o
Among 69 RANO-evaluable patients:
▪
64% ORR and 91% clinical benefit rate (complete response + partial response/unconfirmed partial response + stable disease)
•
4% (n=3) confirmed complete responses
•
59% (n=41) partial responses (31 confirmed and 10 unconfirmed)
•
28% (n=19) patients with stable disease
▪
86% (n=59) of patients had a BRAF fusion alteration, for which there are no approved systemic therapies, while the remaining 14% (n=10) had a BRAF mutation

o
Safety data, based on 77 treated patients, indicated monotherapy tovorafenib (DAY101) to be generally well-tolerated. The most common side effects reported related to tovorafenib (DAY101) were change in hair color (75%), increased creatine phosphokinase (64%), anemia (46%), fatigue (42%), and maculopapular rash (42%).

o
Among a total of 77 treated patients:
▪
Participants were heavily pretreated, with a median of three prior lines of systemic therapy (range: 1-9)
▪
The median duration of tovorafenib (DAY101) treatment was 8.4 months, with 77% (n=59) of patients on treatment at the time of the data cutoff
▪
Nearly 60% (n=46) of patients had already received at least one prior MAPK inhibitor prior to study participation

•
Patient enrollment continues in the Phase 1b/2 FIRELIGHT-1 trial evaluating tovorafenib (DAY101) as a monotherapy and as a combination with the company’s investigational MEK inhibitor, pimasertib, in adults and adolescents with relapsed, progressive, or refractory solid tumors harboring MAPK pathway aberrations.

Upcoming Milestones

•
Additional follow-up data from the full FIREFLY-1 study population is planned for presentation at a medical meeting in the second quarter of 2023.

•
Anticipated submission of an NDA for tovorafenib (DAY101) to the United States Food and Drug Administration (FDA) in the first half of 2023.

Fourth Quarter and Full Year 2022 Financial Highlights

•
Cash Position: Cash, cash equivalents and short-term investments totaled $342.3 million on December 31, 2022. Based on Day One’s current operating plan, management believes it has sufficient capital resources to fund anticipated operations into 2025.

R&D Expenses: Research and development expenses were $26.0 million and $85.6 million for the fourth quarter and full year ended December 31, 2022, respectively, as compared to $11.2 million and $43.6 million for the same periods in 2021. The increase was primarily due to additional employee compensation costs, clinical trial and pre-commercial manufacturing activities related to Day One’s lead product candidate, tovorafenib (DAY101).

•
G&A Expenses: General and administrative expenses were $16.7 million and $61.3 million for the fourth quarter and full year ended December 31, 2022, respectively, as compared to $10.8 million and $29.2 million for the same periods in 2021. The increase was primarily due to additional employee compensation costs, an ongoing commercial buildout, and professional service expenses to support company growth.

•
Net Loss: Net loss totaled $40.1 million for the fourth quarter of 2022 with non-cash stock compensation expense of $6.8 million, compared to $21.9 million for the fourth quarter of 2021 with non-cash stock compensation expense of $5.1 million. Net loss was $142.2 million for the year ended December 31, 2022, with non-cash stock compensation expense of $27.2 million, compared to $72.8 million for the year ended December 31, 2021, with non-cash stock compensation expense of $13.3 million.

Upcoming Events

43rd Annual TD Cowen Health Care Conference
o
Management will participate in a fireside chat on March 7 at 9:10 a.m. ET. A live and archived audio webcast of the discussion will be available by visiting the Events & Presentations section of the Company’s website.

About Tovorafenib

Tovorafenib is an investigational, oral, brain-penetrant, highly-selective type II pan-RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway, which is being investigated in primary brain tumors or brain metastases of solid tumors. Tovorafenib has been studied in over 325 patients to date. Currently tovorafenib is under evaluation in a pivotal Phase 2 clinical trial (FIREFLY-1) among pediatric, adolescent and young adult patients with relapsed or progressive pLGG, which is an area of considerable unmet need with no approved therapies. Tovorafenib is also being evaluated alone or as a combination therapy for adolescent and adult patient populations with recurrent or progressive solid tumors with MAPK pathway aberrations (FIRELIGHT-1).

Tovorafenib (DAY101)has been granted Breakthrough Therapy and Rare Pediatric Disease designations by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pLGG harboring an activating RAF alteration. Tovorafenib (DAY101) has also received Orphan Drug designation from the FDA for the treatment of malignant glioma, and from the European Commission (EC) for the treatment of glioma.