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contain forward-looking statements that are based on our management's beliefs and assumptions and on information currently available to our management. Forward-looking statements are inherently subject to risks and uncertainties, some of which
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anticipate," "believe," "estimate," "predict," "intend," "potential," "would," "continue," "ongoing" or the negative of these terms or other
comparable terminology. Forward-looking statements include all statements other than statements of historical fact contained in this presentation, including information concerning our future financial performance, including the sufficiency of our
cash and cash equivalents to fund our operations, business plans and objectives, timing and success of our planned nonclinical and clinical development activities, timing and results of nonclinical studies and clinical trials, efficacy and safety
profile of our product candidates, the execution of the Phase 2 clinical trial for DAY101 as designed, any expectations about safety, efficacy, timing and ability to complete clinical trials and to obtain regulatory approvals for DAY101 and other
candidates in development, the ability of DAY101 to treat pLGG or related indications, the potential therapeutic benefits and economic value of our product candidates, potential growth opportunities, competitive position, industry environment and
potential market opportunities, our ability to protect intellectual property, and the impact of the COVID-19 pandemic on our business and operations. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and
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forward-looking statements. In addition, statements that "we believe" and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this
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review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements. Furthermore, if our forward-looking statements prove to be inaccurate, the
inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans
in any specified time frame, or at all. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. This presentation also contains
estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue
weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Day One
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Day One: Developing Targeted Therapies That Address The Urgent Needs of
Children With Cancer Mission That Tovorafenib (DAY101) 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, with cancer, from day one and every pan-RAF inhibitor in-licensed for combination trials day after Being studied as tablets and Projected cash runway into 2025 Develop medicines for genomically-
pediatric-friendly liquid suspension Multiple key milestones: defined cancers Breakthrough Therapy Designation Top-line data from FIREFLY-1 Establish first-in-class position Rare Pediatric Disease Designation
trial in Q1 2023, NDA through rapid pediatric registration submission in 1H 2023, if data Orphan Drug Designation (US/EU) Expand to adolescent and adult are supportive populations in parallel and pursue First patient dosed in
frontline those opportunities with the same pLGG, Phase 3 (FIREFLY-2 commitment we do for children /LOGGIC) trial expected Q3 2022 Day One Biopharmaceuticals 3
Pediatric Markets Create Opportunity for High Impact and Capital
Efficiency Regulatory and Rapid clinical development reimbursement tailwinds Lack of approved products create Early engagement with global potential first-in-class opportunities regulatory authorities Pricing flexibility for
important new Small trials and clear endpoints therapies that permit rapid development to clinical proof-of-concept and Supportive and engaged advocacy potential approval and investigator community desiring better treatment options
Enriched responder populations informed by underlying biology Many pediatric tumors are genetically simple and genomically stable Genetic alterations are often oncogenic Day One Biopharmaceuticals 4
A Senior Team with Deep Experience Developing and Commercializing
Products in Pediatric and Adult Oncology Markets Jeremy Bender, PhD, MBA Samuel Blackman, MD, PhD Charles York II, MBA Chief Executive Officer Chief Medical Officer & Founder Chief Operating and Financial Officer VP of Corporate Development at
Gilead; COO Tizona Pediatric Heme/Onc and Neuro-Onc; Oncology Clinical CFO and Head of Corporate Development at Aeglea; Therapeutics; CBO Sutro Biopharma; founding Board Development at Mavupharma, Silverback, Juno, Seattle Consulting CFO at
Bridgepoint Consulting; member of VaxCyte Genetics, GSK PricewaterhouseCoopers Lisa Bowers Mike Preigh, PhD Davy Chiodin, PharmD Jaa Roberson Chief Commercial Officer Chief Technical Officer Chief Development Officer Chief People Officer CEO of Rhia
Ventures, COO of The Tara Head of CMC at Array for 10+ years. VP Regulatory Science, Acerta/AZ; Global Head of Human Resources at Bellicum Health Foundation, VP of the North Brought >20 drug candidates to IND & Regulatory Leader, Pediatric
Oncology, Pharmaceuticals; Human Resources Roles American Supply Chain and Commercial clinical development Roche/Genentech at Achaogen, Roche/Genentech Leader at Genentech Day One Biopharmaceuticals 5
Our Pipeline Recent & Product Candidate Indication Preclinical Phase
1 Phase 2 Phase 3 Anticipated Milestones Pivotal cohort enrollment complete: May 2022 Initial data presented: 1 Relapsed pLGG FIREFLY-1 (pivotal) June 2022 Tovorafenib (DAY101) Topline data expected: Type II Pan-RAF Inhibitor Q1 2023 FDA
Breakthrough Therapy Designation for relapsed pLGG First patient dosed FIREFLY-2 (pivotal) expected: Q3 2022 Frontline pLGG FDA Rare Pediatric Disease Designation (PRV Eligible) for pLGG FDA Orphan Drug Designation for gliomas
RAF-altered First patient dosed: EC Orphan Designation for gliomas FIRELIGHT-1* November 2021 2 solid tumors (monotherapy) MAPK-altered First patient dosed: Pimasertib FIRELIGHT-1* May 2022 3 solid tumors MEK 1/2 Inhibitor (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 Biopharmaceuticals 6
Tovorafenib (DAY101) Type II Pan-RAF Inhibitor Day One
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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 1,2 with 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 1-4 chronic 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. Ostrum QT et al., Neuro Oncol. 2015; 16(Suppl 10):x1-x36; 2. De Blank P. et al., Curr Opin Pediatr. 2019 Feb; 31(1):21-27. 3. Jones DTW et al., Cancer Res. 2008; 68:8673-77. 4. 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 wild- RAF RAF fusion type fusions and BRAF V600E mutations RAF Tovorafenib mutation Tablet and pediatric-friendly liquid suspension; once weekly dosing MEK Currently approved type I RAFi are
indicated for use only in adults and patients 6+ with relapsed tumors harboring a BRAF V600 ERK mutation Type I RAF inhibitors cause paradoxical MAPK activation in the setting of wild-type Proliferation and survival Proliferation and
survival Proliferation and survival RAF, increasing the risk of tumor growth in BRAF fusion-driven and other non-V600 mutant cancers 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 Biopharmaceuticals 9
The Current pLGG Treatment Paradigm Reflects the Unrelenting Nature of
this Chronic Brain Tumor Presentation Surgical Intervention 1L 2L 3L 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. Source: Physician Interviews, Bandopadhayay et al. Pediatric Blood Cancer. 2014; Sievert and Fischer. J Child Neurol. 2009; ClearView Analysis. GTR: Gross Total Resection
1Molecular 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 10
Pivotal Phase 2 Trial Of Monotherapy Tovorafenib (DAY101) In Relapsed
Or Progressive pLGG (FIREFLY-1) Trial Design Endpoints (Pivotal Arm 1) Three arm, open-label, global registrational phase 2 trial Primary endpoint: ORR based on RANO criteria, assessed by blinded independent central review
Pivotal arm 1 (recurrent/progressive LGG): n = ~ 60 RANO-evaluable patients aged 6 months to 25 years harboring a KIAA1549-BRAF Secondary endpoints: ORR by RAPNO criteria; PFS; safety fusion or BRAF V600 mutation Arm 2 (expanded
access recurrent/progressive LGG): patients aged 6 months to 25 years harboring an activating RAF alteration Arm 3 (extracranial solid tumors): patients aged 6 months to 25 years harboring an activating RAF fusion Clinical and radiological
evaluations at baseline, and every rd nd 3 cycle for pLGG and every 2 cycle for solid tumors Enrollment/ Day -28 to 0 Screening Baseline End of Trial (C1D1) Study Drug Administration After Cycle 27: patients may either continue C27D1 2
treatment or enter drug holiday period at any time 420mg/m QW (at discretion of Investigator) Eligibility evaluation Treatment period: minimum of 2 years or until progression or toxicity/intolerability Abbreviations: C, cycle; D, day; LGG, low-grade
glioma; ORR, objective response rate; Day One Biopharmaceuticals 11 PFS, progression-free survival. NCT04775485
Baseline Characteristics Location (n=25) Characteristic Arm 1 (N=25)
Deep midline structures Optic pathway 12% Median age, years (range) 8 (3-18) 52% Sex, n (%) Other Male 13 (52) 16% Female 12 (48) Hypothalamus Race, n (%) 8% Cerebellum Black or African American 1 (4) 4% Asian 2 (8) Brain stem White 15 (60) 8%
Other* 7 (28) Karnofsky/Lansky performance status, n (%) BRAF alteration (n=25) 50-70 1 (4) 80-100 24 (96) BRAF V600E Number of lines of prior therapy 16% Median (range) 3 (1-9) 1, n (%) 5 (20) 2, n (%) 6 (24) 3, n (%) 14 (56) BRAF
fusion Prior MAPK pathway targeted therapy, n (%) 84% Yes 18 (72) No 7 (28) Apr 14, 2022 data cutoff; *Includes 4 patients with race not specified. Includes 2 patients with BRAF duplication and 1 with BRAF rearrangement per fluorescence in
situ hybridization. MAPK, mitogen-activated protein kinase; prior MAPK pathway targeted therapy indicates either prior MEKi and/or prior type I RAFi therapy. Day One Biopharmaceuticals 12
Tumor Response To Tovorafenib (DAY101) For All Patients With RANO-
Evaluable Lesions (n=22)* RANO Evaluable Response (IRC) N=22* ORR (95% CI) 64% (41-83) BRAF fusion (n=20) 60% BRAF V600E (n=2) 100% # CBR 91% Best overall response PR (13/22) 59% uPR (1/22) 5% SD (6/22) 27% Apr 14, 2022 data cutoff. Total % of
response maybe may be different than the sum of the individual overall response due to rounding. *3/25 patients lacked evaluable lesions per RANO criteria based on IRC evaluation. Progressive disease due to presence of new lesions. #patients
with best overall response of CR, PR/uPR and SD. CBR, clinical benefit rate; IRC, independent radiological review committee; ORR, overall response rate; MAPK, mitogen-activated protein kinase; PR, partial response; SD, stable disease; uPR,
unconfirmed partial response Day One Biopharmaceuticals 13
Duration of Tovorafenib (DAY101) Therapy For All Patients with RANO-
Evaluable Lesions (n=22) 17/22 patients remain on therapy All responders remain on treatment Day One Biopharmaceuticals 14 Apr 14, 2022 data cutoff.
Individual Patient Tumor Change From Baseline (n=22 RANO-Evaluable By
Blinded Independent Central Review) PD SD PR CR Apr 14, 2022 data cutoff. RANO PD = +25% change from baseline; RANO SD = <+24% Months to > -50% change from baseline; RANO PR = -50% change from baseline; RANO CR = Day One
Biopharmaceuticals 15 -100% change from baseline. Percent change from baseline (%)
Tovorafenib (DAY101) Safety Data For the First 25 Enrolled Patients
(TEAEs 25% Any Grade) Treatment-emergent AEs Treatment-related AEs Preferred term, n (%) Any grade Grade 3 Any grade Grade 3 Most treatment-emergent AEs were Blood creatine phosphokinase increased 20 (80) 2 (8) 18 (72) 2
(8) grade 1 or 2 (96%) Hair color changes 17 (68) - 17 (68) - Anemia 14 (56) 3 (12) 10 (40) 2 (8) Other important treatment-emergent Aspartate aminotransferase increased 14 (56) - 12 (48) - AEs included: Vomiting 14 (56) 2 (8) 6 (24) 1 (4)
Decreased weight (24%) Rash* 13 (52) 3 (12) 13 (52) 3 (12) Blood lactate dehydrogenase increased 12 (48) - 9 (36) - Decreased appetite (16%) Headache 10 40) - 3 (12) - Hyponatremia (16%) Dry skin 9 (36) - 7 (28) - Epistaxis 9
(36) - 4 (16) - 7 patients (28%) required dose modifications Constipation 8 (32) - 5 (20) - due to treatment-related AEs Hypocalcemia 8 (32) - 6 (24) - Nausea 8 (32) - 3 (12) - No patient discontinued treatment due to AEs Alanine
aminotransferase increased 7 (28) 1 (4) 4 (16) 1 (4) Fatigue 7 (28) - 7 (28) - Apr 14, 2022 data cutoff. AE, adverse event. TEAE, treatment-emergent adverse event. *Includes maculopapular and erythematous rash 16 Day One Biopharmaceuticals
Key Takeaways Encouraging initial efficacy data from FIREFLY-1
for pediatric patients with relapsed LGG harboring BRAF fusion or BRAF V600 mutation, for whom there is no standard-of-care and no approved agents for the majority of patients 64% ORR and 91% clinical benefit rate (partial
response/unconfirmed partial response + stable disease) in the 22 RANO-evaluable patients: 14 partial responses (13 confirmed responses and 1 unconfirmed response) 6 patients with stable disease All patients with stable
disease (n=6) were noted to have tumor shrinkage, ranging between 19% and 43% Responses were observed in patients with both BRAF fusions and BRAF V600E mutations who received prior MAPK-targeted therapy The median-time-to-response
was 2.8 months A heavily-pretreated population, with a median of 3 prior lines of therapy (range: 1-9) All patients who responded remain on therapy (n=14) and no patients have discontinued treatment due to treatment-related adverse
events Initial safety data, based on the first 25 patients, indicated monotherapy tovorafenib (DAY101) to be generally well-tolerated Majority of AEs were grade 1 or 2; most common treatment-related AEs were CPK elevation, rash, and
hair color changes Treatment-related AEs of grade 3 or greater occurred in nine patients (36%) Plan to present additional initial study results from FIREFLY-1 at an upcoming medical conference in 2H 2022 Topline results from
the full registrational cohort (n=~60) of FIREFLY-1 expected to be available 1Q 2023, with NDA submission planned for 1H 2023 Early results from FIREFLY-1 support plan to evaluate tovorafenib (DAY101) in parallel Phase 3 frontline pLGG study
(FIREFLY-2) Primary endpoint of ORR based on RANO criteria, assessed by blinded independent central review Day One Biopharmaceuticals 17