Full Press Release Details
All Ages March 2023 Day One Biopharmaceuticals 1
Disclaimer This presentation and the accompanying oral commentary
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
cannot be predicted or quantified. In some cases, you can identify forward-looking statements by terminology such as "may," "will," "should," "could," "expect," "plan,"
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, cash equivalents and investments 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 profiles of our product candidates, execution of the Phase 2 clinical trial for tovorafenib and the Phase 1b/2 clinical trial for tovorafenib and pimasertib as designed, any expectations about safety, efficacy, timing and 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 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 global business or macroeconomic
conditions, including as a result of the COVID-19 pandemic, inflation and rising interest rates, on our business and operations. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors. It is
not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any
forward-looking statements we may make. These factors, together with those that are described under the heading "Risk Factors" contained in our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission
("SEC") and other documents we file from time to time with the SEC, may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our 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 presentation, and although we
believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted a thorough inquiry into, or 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 Biopharmaceuticals 2
Cancer Drug Development for People of All Ages 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, in- with cancer,
from day one and every pan-RAF inhibitor licensed for combination trials day after Being studied as tablets and Projected cash runway into 2025 Develop medicines for genomically- pediatric-friendly liquid suspension
Upcoming key milestones defined cancers Breakthrough Therapy Designation Pre-NDA meeting in Q2 2023 Establish first-in-class position Rare Pediatric Disease Designation Planned NDA submission in Q2 through
rapid pediatric registration 2023 Orphan Drug Designation (US/EU) Expand to adolescent and adult NDA data set will include populations in parallel and pursue additional follow up with data to those opportunities with the same
be presented at a medical meeting commitment we do for children 1 in Q2 2023 1 NDA data set will include analysis of primary (ORR by RANO-HGG) and secondary (ORR by RAPNO, Day One Biopharmaceuticals 3 PFS) efficacy endpoints, safety, and exploratory
analyses (including ORR by RANO-LGG).
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 Mike Preigh, PhD Adam Dubow Davy Chiodin, PharmD Jaa Roberson Chief Technical Officer General Counsel Chief Development Officer Chief People Officer Head of CMC at Array
for 10+ years. Brought Chief Compliance & Ethics Officer at Bristol VP Regulatory Science, Acerta/AZ; Global Head of Human Resources at Bellicum >20 drug candidates to IND & clinical Myers Squibb (BMS); Legal leadership roles at
Regulatory Leader, Pediatric Oncology, Pharmaceuticals; Human Resources Roles at development BMS in the U.S., Asia and Europe; Partner at Roche/Genentech Achaogen, Roche/Genentech Sedgwick, Detert, Moran & Arnold Day One Biopharmaceuticals
Our Pipeline Recent & Product Candidate Indication Preclinical Phase
1 Phase 2 Phase 3 Anticipated Milestones Topline data presented: January 2023 Pre-NDA meeting & NDA 1 Relapsed pLGG FIREFLY-1 (pivotal) submission planned: Q2 2023 Tovorafenib (DAY101) NDA data set presentation Type II Pan-RAF Inhibitor planned:
Q2 2023 FDA Breakthrough Therapy Designation for relapsed pLGG First patient dosed: FIREFLY-2 (pivotal) Frontline pLGG March 2023 FDA Rare Pediatric Disease Designation (PRV Eligible) for pLGG FDA Orphan Drug Designation for
malignant glioma First patient dosed: RAF-altered November 2021 EC Orphan Designation for glioma FIRELIGHT-1* 2 Abstract accepted for solid tumors presentation: Q2 2023 (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 5
Tovorafenib (DAY101) Type II Pan-RAF Inhibitor Day One
Biopharmaceuticals 6
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
Biopharmaceuticals 7
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 MEK Once weekly dosing Currently approved type I RAFi
are indicated for use in patients with tumors bearing V600E ERK mutations Type I RAF inhibitors cause paradoxical Proliferation and survival Proliferation and survival MAPK activation in the setting of wild-type 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 8
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 ~20% Other Other Other (<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 9
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-HGG criteria, assessed by blinded independent central review
Pivotal Arm 1 (recurrent/progressive pLGG): n=69 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; PFS, Day One Biopharmaceuticals 10 progression-free survival. RANO-HGG, response assessment for neuro-oncology-high grade glioma NCT04775485
FIREFLY-1 Baseline Patient Characteristics Location (n=77) Cerebral
hemisphere Deep midline structures 8% 12% Topline Data Characteristic Arm 1 (N=77) Other 16% Median age, years (range) 8 (2-21) BRAF alteration, n (%) Optic pathway Cerebellum 51% BRAF V600E 13 (17) 6% BRAF Fusion 64 (83) Brain stem 8%
Median number of lines of prior therapy (range) 3 (1-9) BRAF alteration (n=77) Prior MAPK pathway targeted therapy, n (%) BRAF V600E Yes 46 (60) 17% No 31 (40) Geography, n (%) U.S. 27 (35) BRAF fusion Ex-U.S. 50 (65) 83% Sep 28, 2022 data
cutoff. Includes 8 patients with BRAF duplication or BRAF rearrangement. MAPK, mitogen-activated protein kinase; prior MAPK pathway targeted therapy indicates either prior MEKi and/or prior type I RAFi therapy. Day One Biopharmaceuticals
Topline Data from Ongoing Pivotal Phase 2 FIREFLY-1 Trial The primary
endpoint of the FIREFLY-1 trial is overall response rate (ORR) by Response Assessment for Neuro-Oncology-High Grade Glioma (RANO- HGG) criteria as assessed by blinded independent central review. In the 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 Safety data, based on 77 treated patients, indicated
monotherapy tovorafenib to be generally well-tolerated. The most common side effects reported as related to tovorafenib were change in hair color (75%), increased creatine phosphokinase (64%), anemia (46%), fatigue (42%) and maculopapular
rash (42%) 3 patients (3.9%) discontinued treatment due to adverse events, of which 2 (2.6%) were deemed to be related to tovorafenib 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 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 Sep 28, 2022 data cutoff. CR, complete response. PR, partial response. SD, stable disease. Day One Biopharmaceuticals 12
Incidence and Prevalence of BRAF-altered pLGG in the U.S. 2020 2017
Estimated Incidence Estimated SEER Prevalence Under 25 Under 25 1 US Population ~105,000,000 NA 2 3 Rate of CNS Tumors (0.00521%) ~5,500 ~130,000 2 Gliomas (63%) ~3,500 ~82,000 2 Low Grade (77%) ~2,600 ~63,000 2 Has Received Drug Tx (58%) ~1,500
~36,000 2 BRAF Altered (70%) ~1,100 ~26,000 ~1,100 ~26,000 Estimated Annual Incidence Estimated Prevalence 1 2 3 . US Census; CBTRUS, Qaddoumi et al 2009, Schreck et al 2019, ClearView Analysis; SEER US complete Estimated annual incidence and
estimated prevalence are Day prevalence counts of patients aged under 25 with Brain and Other Nervous Systems tumors as of January 1, 2017. One calculations based on publicly available data. 13 Day One Biopharmaceuticals
FIREFLY-2/LOGGIC Pivotal Phase 3 Trial of Tovorafenib (DAY101) in Newly
Diagnosed pLGG Day One Biopharmaceuticals 14
FIREFLY-2/LOGGIC Pivotal Phase 3 Trial of Tovorafenib (DAY101) in Newly
Diagnosed pLGG Trial Design Endpoints Randomized, global, registrational Phase 3 trial of monotherapy tovorafenib Primary endpoint: ORR based on RANO-LGG criteria, assessed 1 (DAY101) vs SoC chemotherapy by blinded independent
central review Eligibility: Patients aged 6 months to <25 years with LGG harboring a RAF The ORR primary analysis is expected to occur ~12 months after alteration and requiring first-line systemic therapy the last patient
randomized Tovorafenib (DAY101) available as tablets and pediatric-friendly liquid suspension Key secondary endpoints: PFS and DoR by RANO criteria, ORR by Patients who progress after stopping tovorafenib (DAY101) may be
re-challenged RAPNO criteria Patients who progress in the SoC arm during or post-treatment may cross-over to Other secondary endpoints: changes in neurological and visual receive tovorafenib function, safety, and tolerability
Key exploratory objectives: QoL and health utilization measures 2 Non-resectable or sub-total Tovorafenib, 420mg/m QW resected LGG (not to exceed 600 mg) AND Long-term follow-up (48 months) Requiring first-line systemic Stratified by therapy
Location of tumor Investigator's choice of Genomic alteration vincristine/carboplatin* or N 400 CDKN2A status vinblastine Infant CHG diagnosis * COG or SIOPe-LGG regimen 1 1Primary endpoint of FIREFLY-2 will be ORR by
RANO-LGG (2017) following full approval by FDA on March Abbreviations: CHG, chiasmatic, hypothalamic glioma; DoR, duration of response; LGG, low-grade glioma; ORR, Day One Biopharmaceuticals 15 16, 2023 of dabrafenib with trametinib in pediatric
patients with low-grade glioma with a BRAF V600E objective response rate; QoL, quality of life; QW, once weekly; SoC, standard of care. mutation who require systemic therapy based on a study with the same primary endpoint. 1:1
FIREFLY-2/LOGGIC: Pivotal Phase 3 Study Of Tovorafenib (DAY101) In
Newly Diagnosed pLGG Collaboration between Day One and the LOGGIC consortium, internationally recognized experts in pLGG research Coupled with the LOGGIC-CORE molecular diagnostic program Worked jointly on the study design
and discussions with the U.S. and EU regulatory authorities Approximately 100 potential sites (~65 from the LOGGIC consortium) ~20 ~65 Sites Sites ~5 Sites ~10 Sites Day One Biopharmaceuticals 16
Our Pipeline Recent & Product Candidate Indication Preclinical