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All Ages June 2023 Day One Biopharmaceuticals
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ability to complete clinical trials and to obtain regulatory approvals for tovorafenib and other candidates in development, the ability of tovorafenib to treat pediatric low-grade glioma (pLGG) or related indications, the potential therapeutic
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a high degree of uncertainty and risk. Day One Biopharmaceuticals 2
Cancer Drug Development For People Of All Ages Tovorafenib (DAY101)
Mission That Growing Portfolio and Runway Creates Value Lead Program Beyond Clinical Milestones Day One's mission is to help children Investigational, oral, CNS-penetrant Two clinical-stage MEKi assets, in- with cancer,
from day one and every Type II RAF inhibitor licensed for combination trials day after 1 Being developed as tablets and Projected cash runway into 2026 Develop medicines for genomically- pediatric-friendly liquid suspension
Key FIREFLY-1 milestones defined cancers Breakthrough Therapy Designation - Initiated rolling NDA submission in Establish first-in-class position 2 May 2023 Rare Pediatric Disease Designation through rapid
pediatric registration - New clinical data presented in June Orphan Drug Designation (US/EU) Expand to adolescent and adult 2023 populations in parallel and pursue - Expected completion of rolling those opportunities with
the same NDA submission in October 2023 commitment we do for children 1 2 With cash, cash equivalents and short-term investments as of March 31, 2023 and approximately $172.5 million in gross proceeds from follow-on offering in June 2023. NDA data
set will include analysis of primary (ORR by RANO-HGG) and secondary (ORR by RAPNO-LGG, PFS) efficacy endpoints, safety, and exploratory analyses (including ORR by RANO-LGG). Day One Biopharmaceuticals 3
Our Pipeline Recent & Product Candidate Indication Preclinical Phase
1 Phase 2 Phase 3 Anticipated Milestones Initiated rolling NDA submission: May 2023 Tovorafenib (DAY101) New clinical data presented: 1 Relapsed pLGG Type II Pan-RAF Inhibitor FIREFLY-1 (pivotal) June 2023 Expected rolling NDA submission FDA
Breakthrough Therapy complete: October 2023 Designation for relapsed pLGG FDA Rare Pediatric Disease First patient dosed: Designation (PRV Eligible) for Frontline pLGG FIREFLY-2 (pivotal) March 2023 pLGG FDA Orphan Drug Designation
for malignant glioma First patient dosed: EC Orphan Designation for glioma RAF-altered November 2021 2 solid tumors FIRELIGHT-1* Poster presented: (monotherapy) April 2023 Pimasertib MAPK-altered 3 First patient dosed: MEK 1/2 Inhibitor
FIRELIGHT-1* solid tumors May 2022 (Combo w/tovorafenib) 1 2 3 *Includes patients 12 years of age. FIREFLY-1 Arm 1 expected to support registration. DAY101 adult monotherapy Phase 1 dose escalation and expansion trial previously completed.
Pimasertib Phase 1 dose escalation and expansion trial previously completed. pLGG, pediatric low-grade glioma. Tovorafenib and Pimasertib are investigational products. Safety and efficacy have not been established by any health authority. Day One
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Tovorafenib (DAY101) Type II RAF Inhibitor Day One
Pediatric Low-Grade Gliomas (pLGG) Despite being the most common
brain tumor in children, there are no approved agents and no standard-of-care for the majority of patients with 1,2 relapsed/progressive disease ~70% of patients will require systemic therapy Patients have a high rate of recurrence
and are frequently treated with multiple lines of systemic therapy over the course of their disease 3 The majority of pLGGs are driven by BRAF alterations ~85% of BRAF-altered tumors harbor a KIAA1549-BRAF gene fusion ~15%
are driven by BRAF V600E mutation Despite low-grade histology and high long-term survival, pLGGs are chronic 1-4 and relentless Goal of therapy is to stabilize or shrink tumors while minimizing treatment- associated toxicities from
surgery, chemotherapy, and radiation Many patients today suffer profound tumor and treatment-associated morbidity and significant late effects that persist throughout life 6 y/o with large relapsed BRAF fusion-positive optic pathway glioma 1
2 3 4 Ostrum QT et al., Neuro Oncol. 2015; 16(Suppl 10):x1-x36; De Blank P. et al., Curr Opin Pediatr. 2019 Feb; 31(1):21-27. Jones DTW et al., Cancer Res. 2008; 68:8673-77. Traunwieser T et al., Neurooncol Adv. 2020; 2:vdaa094. Day One
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Tovorafenib (DAY101) Inhibits Both BRAF Fusions And BRAF V600 Mutations
Tovorafenib (DAY101) is an investigational, MAPK pathway RAS-independent activation of the MAPK pathway oral, selective, CNS-penetrant, type II pan- RAF inhibitor that was designed to inhibit RAS both monomeric and dimeric RAF kinase
Activity in tumors driven by both RAF RAF RAF fusion fusions and BRAF V600E mutations RAF Tovorafenib mutation Tablet and pediatric-friendly liquid suspension MEK Once weekly dosing Currently approved type I BRAFi are
indicated for use in patients with tumors bearing BRAF ERK V600E mutations Type I BRAF inhibitors cause paradoxical Proliferation and survival Proliferation and survival Proliferation and survival MAPK activation in the setting of wild-type
RAF, increasing the risk of tumor growth in BRAF fusion-driven Source: 1. Sun Y et al., Neuro Oncol. 2017; 19: 774-85; 2. Sievart AJ et al., PNAS. 2013; 110:5957-62; 3. Karajannis MA et al., Neuro Oncol 2014;16(10):1408-16 Day One
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The Current pLGG Treatment Paradigm Reflects The Unrelenting Nature Of
This Chronic Brain Tumor 1L 2L 3L Presentation Surgical Intervention ~35% ~20% Targeted Tx Targeted Tx Targeted Tx GTR No Recurrence (5-10%) (40-50%) (40-50%) 1 Biopsy (>95%) Suspected ~65% ~50% ~50% pLGG Partial Eventual Additional lines
Chemo Chemo Chemo Resection Recurrence of therapy ~40% ~80% (~90%) (~50%) (~35%) Molecular Testing Biopsy Only Other Other Other ~20% (<5%) (<5%) (<20%) No Biopsy (~5%) Response, Response, ~35% no recurrence ~50% no recurrence Because many
pLGGs undergo senescence when patients reach their 20s, the goal of therapy is to maximize tumor control while minimizing treatment-associated toxicities from surgery, chemotherapy, and radiation. As a result, a large number of pLGG patients will
undergo multiple lines of systemic therapy over the course of their disease. 1 Source: Physician Interviews, Bandopadhayay et al. Pediatric Blood Cancer. 2014; Sievert and Fischer. J Child Neurol. 2009; ClearView Analysis. GTR: Gross Total Resection
Molecular testing of biopsied samples occurs in all patients. Kandels et. al. Retrospective analysis of comprehensive SIOP registry; Hargrave et. al. Phase I/II;Fangusaro et. al. Phase II Day One Biopharmaceuticals 8
Progress Of FIREFLY-1 Program: Monotherapy Tovorafenib In Relapsed pLGG
Updated Clinical Data from FIREFLY-1 Trial Presented at ASCO Pre-NDA Meeting (Jun 2023) Interim Analysis Data (Apr 2023) from FIREFLY-1 Trial (Jun 2022) First Patient Dosed in FIREFLY-1 Trial (May 2021) Initiated Rolling NDA Expected Topline Data
from Submission Completion of FIREFLY-1 Trial Pivotal Cohort (May 2023) Rolling NDA (Jan 2023) Enrollment Complete in Submission FIREFLY-1 Trial (Oct 2023) Initial Discussion (May 2022) with FDA including FIREFLY-1 Trial Design (Apr 2020) Day One
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Pivotal Phase 2 Trial Of Monotherapy Tovorafenib (DAY101) In Relapsed
Or Progressive pLGG (FIREFLY-1) Trial Design Endpoints (Pivotal Arm 1) 1 Three arm, open-label, global registrational phase 2 trial Primary endpoint: ORR based on RANO-HGG , assessed by blinded independent central review
Pivotal Arm 1 (recurrent/progressive pLGG, n=77): harboring a 2 KIAA1549-BRAF fusion or BRAF V600E mutation Secondary endpoints: ORR by RAPNO-LGG assessed by blinded independent central review; PFS, DoR; TTR, CBR; safety Arm 2
(expanded access recurrent/progressive LGG, n=59): harboring 3 an activating RAF alteration Exploratory analyses: ORR and CBR by RANO-LGG assessed by blinded independent central review Arm 3 (extracranial solid tumors): harboring an
activating RAF fusion Key Inclusion Criteria Clinical and radiological evaluations at baseline, and every rd nd 3 cycle for pLGG and every 2 cycle for solid tumors 6 months - 25 years of age RAF-altered tumor Enrollment/ Day
-28 to 0 1 prior line of systemic Screening Baseline End of Trial therapy with radiographic (C1D1) Study Drug Administration After Cycle 27: patients may either continue progression C27D1 2 treatment or enter drug holiday period
at any time 420mg/m QW (not to exceed 600mg), Prior use of MAPK pathway (at discretion of investigator) QW in 28-day cycles targeted therapy was permitted Eligibility evaluation Treatment period: minimum of 2 years or until progression or
toxicity/intolerability 1 2 3 Dec 22, 2022 data cutoff. Wen PY, et al. J Clin Oncol. 2010;28(11):1963-1972. Fangusaro J, et al. Lancet Oncol. 2020;21(6):e305-316. van den Bent MJ, et al. Lancet Oncol. 2011;12(6):583-593. Abbreviations: CBR,
clinical benefit rate; IRC, independent review committee; C, cycle; D, day; LGG, low-grade glioma; ORR, objective response rate; PFS, progression-free survival; DoR, duration of response; QW, once weekly; TTR, time to response; RANO, Response
Assessment in Neuro-Oncology; RAPNO, Response Assessment in Pediatric Neuro-Oncology; MAPK, mitogen-activated protein kinase. For more information, please refer to NCT04775485 Day One Biopharmaceuticals 10
FIREFLY-1 Baseline Patient Characteristics Location (n=77) Deep midline
structures Characteristic Arm 1 (n=77) 12% Optic pathway 51% Median age, years (range) 8 (2-21) Other Sex, n (%) * 16% Male 40 (52) Cerebral hemisphere Female 37 (48) 8% Cerebellum Race, n (%) 6% Brain stem Black or African American 2 (3) 8% Asian 5
(6) White 41 (53) BRAF alteration (n=77) Multiple 3 (4) Other 6 (8) BRAF V600E Not reported 20 (26) 17% Number of lines of prior systemic therapy Median (range) 2 (1-9) # BRAF fusion 1, n (%) 18 (23) 83% 2, n (%) 21 (27) 3, n (%) 38 (49)
Prior MAPK pathway targeted therapy, n (%) 46 (60) Dec 22, 2022 data cutoff. *Includes tumors that were extending into multiple regions of the brain, leptomeningeal disease, and/or spinal disease. #Includes 6 patients with BRAF duplication and 2
with BRAF rearrangement per FISH (Fluorescence in situ hybridization) or ISH (in situ hybridization). MAPK, mitogen-activated protein kinase. Day One Biopharmaceuticals 11
Tumor Response To Tovorafenib (DAY101) For All Patients With RANO-HGG
Evaluable Lesions (n=69) 1 RANO-HGG Response (IRC) Evaluable n=69 ORR (cCR + cPR + uPR), n (%) 46 (67%)* Clinical benefit rate, n (%) cCR, cPR/uPR, or SD 64 (93%) cCR, cPR/uPR, or SD for 12 mo+ 49 (71%) Best overall response, n (%) CR 4 (6%) PR
(includes 3 uPR) 42 (61%) SD 18 (26%) PD 4 (6%) Not evaluable 1 (1%) All 3 patients with uPR remain on treatment as of May 23, 2023 Dec 22, 2022 data cutoff. Percents may not add to 100% due to rounding. Two of 69 patients are not shown in the
waterfall plot; one patient passed away due to progressive disease (not related to tovorafenib) before the first imaging assessment and one did not receive T1 Gd+ 2 1 2 follow-up imaging. *P<0.001 from two-sided exact binomial test to test null
hypothesis of ORR=21% based on Bouffet et al. Wen PY, et al. J Clin Oncol. 2010;28(11):1963-1972. Bouffet E, et al. J Clin Oncol. 2012;30(12):1358-1363. CBR, clinical benefit rate; cCR, confirmed completed response; cPR, confirmed partial response;
CR, complete response; HGG, high-grade glioma; IRC, independent radiology review committee; MAPKi, mitogen-activated protein kinase inhibitor; MR, minor response; ORR, overall response rate; PD, progressive disease; PR, partial response; RANO,
Response Assessment in Neuro-Oncology; SD, stable disease; uPR, unconfirmed partial response. There are 17 patients with stable disease of less than 12 months duration and at the time of the data cutoff, 11 remain on treatment. Day One
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Tumor Response To Tovorafenib (DAY101) For All Patients With RAPNO-LGG
Evaluable Lesions (n=69*) 1 RAPNO-LGG Response (IRC) Evaluable n=69 ORR (cCR + cPR/uPR + cMR/uMR), n (%) 35 (51%) Clinical benefit rate, n (%) cCR, cPR/uPR, cMR/uMR, or SD 60 (87%) cCR, cPR/uPR, cMR/uMR, or SD for 12mo+ 36 (52%) Best overall
response, n (%) CR 0 (0%) PR (includes 4 uPR) 17 (25%) MR (includes 4 uMR) 18 (26%) SD 25 (36%) # PD 8 (12%) Not evaluable 1 (1%) All 4 patients with uPR and 3 patients with uMR remain on treatment as of May 23, 2023 Dec 22, 2022 data cutoff.
Percents may not add to 100% due to rounding. Two of 69 patients not shown in waterfall plot; one patient passed away due to progressive disease (not related to tovorafenib) before the first imaging assessment and one patient had visual progressive
disease but no evaluable T2 measurements at 1 # the time of progression. *Pending adjudication. Fangusaro J, et al. Lancet Oncol. 2020;21(6):e305-316. PD for RAPNO-LGG was not used to determine treatment discontinuation; patients could continue
treatment if there was no PD based on RANO-HGG per investigator's assessment. CBR, clinical benefit rate; cCR, confirmed completed response; cMR, confirmed minor response; cPR, confirmed partial response; CR, complete response; HGG, high-grade
glioma; IRC, independent radiology review committee; LGG, low-grade glioma; MAPKi, mitogen-activated protein kinase inhibitor; MR, minor response; ORR, overall response rate; PD, progressive disease; PR, partial response; RANO, Response Assessment
in Neuro-Oncology; RAPNO, Response Assessment in Pediatric Neuro-Oncology; SD, stable disease; uMR, unconfirmed minor response; uPR, unconfirmed partial response. There are 28 patients with stable disease of less than 12 months duration and at the
time of the data cutoff, 11 remain on treatment. Day One Biopharmaceuticals 13
Tumor Response To Tovorafenib (DAY101) For All Patients With RANO-LGG
Evaluable Lesions (n=76) 1 RANO-LGG Response (IRC) Evaluable n=76 ORR (cCR + cPR/uPR + cMR/uMR), n (%) 37 (49%) Clinical benefit rate, n (%) cCR, cPR/uPR, cMR/uMR, or SD 63 (83%) cCR, cPR/uPR, cMR/uMR, or SD for 12mo+ 39 (51%) Best overall response,
n (%) CR 0 (0%) PR (includes 8 uPR) 20 (26%) MR (includes 2 uMR) 17 (22%) SD 26 (34%) # PD 11 (14%) Not evaluable 2 (3%) All 8 patients with uPR and 2 patients with uMR remain on treatment as of May 23, 2023 # Dec 22, 2022 data cutoff.
Percents may not add to 100% due to rounding. PD for RANO-LGG was not used to determine treatment discontinuation; patients could continue treatment if there was no PD based on RANO-HGG per investigator's assessment. Two of 76 patients are not
shown in the waterfall plot; one 1 patient passed away due to progressive disease (not related to tovorafenib) before the first imaging assessment, and one patient with missing T1 Gd+ imaging at baseline was deemed NE at all timepoints but had a
best SPPD decrease of 65% on T2 imaging. van den Bent MJ, et al. Lancet Oncol. 2011;12(6):583-593. BL, baseline; CBR, clinical benefit rate; cCR, confirmed completed response; cMR, confirmed minor response; cPR, confirmed partial response; CR,
complete response; HGG, high-grade glioma; IRC, independent radiology review committee; LGG, low-grade glioma; MAPKi, mitogen-activated protein kinase inhibitor; MR, minor response; ORR, overall response rate; PD, progressive disease; PR, partial
response; RANO, Response Assessment in Neuro-Oncology; SD, stable disease; SPPD, sum of the products of perpendicular diameters; uMR, unconfirmed minor response; uPR, unconfirmed partial response. There are 27 patients with stable disease of less