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|Item 8.01.|| |
On January 8, 2023, Day One Biopharmaceuticals, Inc. (the “Company”) issued a press release announcing topline data from its ongoing pivotal Phase 2 trial (“FIREFLY-1”) of tovorafenib (DAY101) for pediatric patients with relapsed or progressive low-grade glioma and the Company updated guidance on the planned first patient dosing to the first quarter of 2023 for the Company’s Phase 3 clinical trial (FIREFLY-2/LOGGIC) evaluating tovorafenib as a front-line therapy for patients newly diagnosed with pLGG.
Additionally, the Company has updated its corporate presentation in connection with its participation in the 41st Annual J.P. Morgan Healthcare Conference.
Copies of the press release and the updated corporate presentation materials are attached hereto as Exhibit 99.1 and Exhibit 99.2, respectively, and are incorporated herein by reference.
|Item 9.01.|| |
Financial Statements and Exhibits.
|99.1||Press Release, dated January 8, 2023.|
|104||Cover Page Interactive Data File (embedded within the Inline XBRL document)|
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
|DAY ONE BIOPHARMACEUTICALS, INC.|
|Date: January 9, 2023||By:|
Charles N. York II, M.B.A.
Chief Operating Officer and Chief Financial Officer
Day One Announces Topline Data from Pivotal Phase 2 FIREFLY-1 Trial
Demonstrating Meaningful Responses with Tovorafenib (DAY101) in Recurrent
or Progressive Pediatric Low-Grade Glioma
Overall response rate (ORR) of 64% and clinical benefit rate (CBR) of 91% in 69 heavily-pretreated, RANO-evaluable patients
Median duration of 8.4 months on therapy as of September 28, 2022, with 77% of patients remaining on treatment
Additional data to be presented at a medical meeting in the second quarter of 2023
New Drug Application submission planned for first half of 2023
SOUTH SAN FRANCISCO, Calif., Jan. 8, 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, today announced positive topline results from the ongoing, open-label, pivotal Phase 2 FIREFLY-1 trial evaluating the investigational agent, tovorafenib (DAY101), as a monotherapy in recurrent or progressive pediatric low-grade glioma (pLGG). Pediatric low-grade glioma is the most common brain tumor diagnosed in children and for which there is no standard of care, and for which there are no approved therapies for the majority of patients. Additional data will be submitted for presentation at an upcoming medical meeting in the second quarter of 2023.
The primary endpoint of the FIREFLY-1 trial is overall response rate (ORR) by Response Assessment for Neuro-Oncology (RANO) criteria as assessed by blinded independent central review. Topline results as of September 28, 2022 include:
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
Safety data, based on 77 treated patients, indicated monotherapy tovorafenib to be generally well-tolerated. The most common side effects reported related to tovorafenib were change in hair color (75%), increased creatine phosphokinase (64%), anemia (46%), fatigue (42%) and maculopapular rash (42%).
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
The responses weve observed in the FIREFLY-1 study with weekly monotherapy tovorafenib in children with recurrent or progressive low-grade gliomas are very encouraging, said Samuel Blackman, M.D., Ph.D., co-founder and chief medical officer of Day One. As tovorafenib progresses in the clinic, we want to thank the patients, their families, the clinical investigators, and the advocates who have chosen to participate in the FIREFLY-1 clinical trial and support the development of a potential new treatment for children in need of new therapeutic options.
FIREFLY-1 is evaluating tovorafenib as once-weekly monotherapy in patients aged 6 months to 25 years with recurrent or progressive pLGG. The trial is being conducted in collaboration with the Pacific Pediatric Neuro-Oncology Consortium (PNOC) and is designed to support the potential regulatory approval of tovorafenib.
Based on the efficacy and safety profile of tovorafenib observed to date from the FIREFLY-1 trial population, we plan to submit a New Drug Application in the first half of this year that will include additional follow up from the full study population, said Jeremy Bender, Ph.D., chief executive officer of Day One. We look forward to continuing our discussions with regulatory authorities with the hope of bringing this therapy to children in need of new options as soon as possible.
In addition to FIREFLY-1, Day One is expanding the development of tovorafenib as a front-line therapy for patients newly diagnosed with pLGG. The global, Phase 3, registrational FIREFLY-2/LOGGIC clinical trial is evaluating once-weekly monotherapy tovorafenib in newly-diagnosed patients with pLGG harboring a known activating RAF alteration.
About Pediatric Low-Grade Glioma
Pediatric low-grade glioma (pLGG) is the most common brain tumor diagnosed in children, accounting for 30% 50% of all central nervous system tumors. BRAF wild-type fusions are the most common cancer-causing genomic alterations in pediatric low-grade gliomas. These genomic alterations are also found in several adult and pediatric solid tumors.
Pediatric low-grade glioma can impact a childs health in many ways depending on tumor size and location, including vision loss and motor dysfunction. There are no approved therapies for pLGG, and current treatment approaches are associated with potential acute and life-long adverse effects. While most children with pLGG survive their cancer, children who do not achieve remission following surgery may face years of increasingly aggressive therapies. Due to the indolent nature of pLGG, patients generally receive multiple years of systemic therapy.
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 recurrent 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 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 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.
About the Pacific Pediatric Neuro-Oncology Consortium
The Pacific 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 is a clinical-stage biopharmaceutical company that believes when it comes to pediatric cancer, we can do better. We put kids first and are developing targeted therapies that deliver to their needs. Day One was founded to address a critical unmet need: the dire lack of therapeutic development in pediatric cancer. The Companys name was 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 whats possible for all people living with cancerregardless of agestarting from Day One.
Day One partners with leading clinical oncologists, families, and scientists to identify, acquire, and develop important emerging cancer treatments. The Companys lead product candidate, tovorafenib (DAY101), is an investigational, oral, brain-penetrant, highly-selective type II pan-RAF kinase inhibitor. The Companys pipeline also includes pimasertib, an investigational, oral, highly-selective small molecule inhibitor of mitogen-activated protein kinases 1 and 2 (MEK-1/-2). Day One is based in South San Francisco. For more information, please visit www.dayonebio.com or find the company on LinkedIn or Twitter.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: Day Ones plans to develop cancer therapies, expectations from current clinical trials, the execution of the Phase 2 and Phase 3 clinical trial for tovorafenib as designed, any expectations about safety, efficacy, timing and ability to complete clinical trials, release data results and to obtain regulatory approvals for tovorafenib and other candidates in development, and the ability of tovorafenib to treat pLGG or related indications.
Statements including words such as believe, plan, continue, expect, will, develop, signal, potential, or ongoing and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements.
Forward-looking statements are subject to risks and uncertainties that may cause Day Ones actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties in this press release and other risks set forth in our filings with the Securities and Exchange Commission, including Day Ones ability to develop, obtain regulatory approval for or commercialize any product candidate, Day Ones ability to protect intellectual property, the potential impact of global business or macroeconomic conditions, including as a result of the COVID-19 pandemic, inflation and rising interest rates and the sufficiency of Day Ones cash, cash equivalents and investments to fund its operations. These forward-looking statements speak only as of the date hereof and Day One specifically disclaims any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law.
DAY ONE MEDIA
Laura Cooper, Head of Communications
DAY ONE INVESTORS
Hans Vitzthum, LifeSci Advisors
Exhibit 99.2 Day One Biopharmaceuticals Targeted Therapies for People of All Ages January 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 Quarterly Report on Form 10-Q 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 • Planned NDA submission in • Establish first-in-class position 1H 2023 • Rare Pediatric Disease Designation through rapid pediatric registration • NDA data set will include • Orphan Drug Designation (US/EU) • Expand to adolescent and adult additional follow up with data to populations in parallel and pursue be presented at a medical those opportunities with the same meeting in Q2 2023 commitment we do for children • First patient dosing in pivotal Phase 3 (FIREFLY-2 /LOGGIC), frontline trial expected Q1 2023 Day One Biopharmaceuticals 3
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 4
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: 1H 2023 Tovorafenib (DAY101) NDA data set presentation Type II Pan-RAF Inhibitor planned: Q2 2023 ü FDA Breakthrough Therapy Designation for relapsed pLGG First patient dosing FIREFLY-2 (pivotal) Frontline pLGG expected: Q1 2023 ü FDA Rare Pediatric Disease Designation (PRV Eligible) for pLGG ü FDA Orphan Drug Designation for malignant glioma RAF-altered First patient dosed: ü EC Orphan Designation for glioma FIRELIGHT-1* 2 November 2021 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 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 only in adults and patients 6+ years of ERK age with relapsed tumors harboring a BRAF V600 mutation Proliferation and survival Proliferation and survival Proliferation and survival ‒ Type I RAF inhibitors cause paradoxical MAPK activation in the setting of wild-type 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 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; Day One Biopharmaceuticals 10 PFS, progression-free survival. 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 11
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 (RANO) 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 criteria, assessed by (DAY101) vs SoC chemotherapy 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 Abbreviations: CHG, chiasmatic, hypothalamic glioma; DoR, duration of response; LGG, low-grade Day One Biopharmaceuticals 15 glioma; ORR, objective response rate; QoL, quality of life; QW, once weekly; SoC, standard of care . 1:1 Randomization
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 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: 1H 2023 Tovorafenib (DAY101) NDA data set presentation Type II Pan-RAF Inhibitor planned: Q2 2023 ü FDA Breakthrough Therapy Designation for relapsed pLGG First patient dosing FIREFLY-2 (pivotal) Frontline pLGG expected: Q1 2023 ü FDA Rare Pediatric Disease Designation (PRV Eligible) for pLGG ü FDA Orphan Drug Designation for malignant glioma RAF-altered First patient dosed: ü EC Orphan Designation for glioma FIRELIGHT-1* 2 November 2021 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 17
Next-generation RAF Inhibitors are Unique in Their Ability to Address Adult Cancers Associated with RAF Wild-type Fusions Tovorafenib (DAY101) has demonstrated monotherapy BRAFwt fusion mixed Mullerian clinical activity in KIAA1549:BRAF and SRGAP3:CRAF wild- cancer type fusions in pLGG Activity of BRAF dimer-breaker PLX-8394 in BRAF wild-type fusion melanoma BRAFwt fusion, melanoma Day One/CrownBio internal data E5251-U2001 (Sep 2020) Botton T et al, Cell Reports, 2019 LY3009120: Lilly pan-RAFi Lifirafenib: Beigene pan-RAF/EGFRi CCT196969: CRUK RAF Gouda M et al, CR observed at 1800 mg BID = 3x ”paradox breaker” Springworks 2020 Corp Presentation ESMO 2020 higher total AUC over 900 mg BID Day One Biopharmaceuticals 18
Phase 2 Study of Monotherapy Tovorafenib (DAY101) in Solid Tumors (FIRELIGHT-1) 1 Trial Design Endpoints • Single arm, open-label, global phase 1b/2a trial • Primary endpoint: ORR by RECIST version 1.1 for non-CNS solid tumors and RANO criteria for any CNS tumors • n = 40 patients (approximately) • Secondary endpoints: safety and additional • Eligibility: Patients aged 12 years and older with non- efficacy parameters hematologic tumor with an activating BRAF fusion, CRAF/RAF1 fusion, or CRAF/RAF1 amplification Melanoma cohort Patients with a known BRAF Safety 2 or CRAF/RAF1 fusion, or DAY101 QW until disease progression Follow Up CRAF/RAF1 amplification “Tissue agnostic” cohort Study Drug Administration ≥ 18 years at 600 mg PO QW 2 12 to <18 years at 420mg/m PO QW Abbreviations: ORR, objective response rate; QW, once weekly ; PO, by mouth; BRAF, B-Raf proto-oncogene.0 1. Umbrella master study – DAY101-102 (main protocol) DAY101 and MAPK pathway aberration, Sub-study 1 monotherapy (DAY101-102a), Sub-study 2 MEK combo (DAY101-102b). 2. DAY101 QW until disease progression, intolerable toxicity, withdrawal of consent, or death Day One Biopharmaceuticals 19
Activity of Tovorafenib (DAY101) in SNX8:BRAF Fusion Spindle Cell Sarcoma A male child spindle cell sarcoma, 5-years of age at diagnosis Months -30 -24 -18 -12 -6 0 6 CR PD CR Diagnosis Targeted Therapy BRAF fusion (FISH) Ifosfamide, doxorubicin, Tovorafenib Tovorafenib Subtotal resection dexrazoxane SNX8-BRAF fusion Gemcitabine, docetaxel Proton radiotherapy • After the first dose of Baseline After 2 cycles of tovorafenib tovorafenib (DAY101), the patient experienced grade 2 rash, which resolved in a day following a dose of diphenhydramine • Radiotherapy-related adverse events included hyperpigmentation overlying the spine on the upper back with no skin breaks, and mild dysphagia Data cut off: September 30, 2021 Day One Biopharmaceuticals 20
Strong Scientific Rationale for Combining Tovorafenib (DAY101) with Additional MAPK Pathway Inhibitors BRAF or CRAF BRAF KRAS or NRAS NF1 non-V600 mutant LOF WT fusion MEK MEK RAF/ PI3K/m RAS/RAF/ME PI3K/ Signaling RAL MEK/ERK TOR K/ERK mTOR pathways ERK ERK Proliferation, survival Proliferation, survival Proliferation, survival Proliferation, survival KRAS - G12Ci MEKi or Potential Type II RAFi + or Type II RAFi + MEKi Type II RAFi + MEKi Type II RAFi + SHP2i combinations or SHP2i SHP2i Non V600 BRAF dimers are BRAF fusion dimers are Targeting multiple nodes of Targeting multiple pathways effectively inhibited by type II, effectively inhibited by type II, MAPK pathway will drive deeper will drive deeper response Rationale but not type I, RAFi but not type I RAFi and more durable response Day One Biopharmaceuticals 21
Pimasertib MEK1/2 Inhibitor Day One Biopharmaceuticals 22
Pimasertib: Investigational Allosteric MEK1/2 Inhibitor with Demonstrated Activity in MAPK-driven Solid Tumors RTKS GF • Pimasertib is an investigational orally-bioavailable, selective, non-competitive MEK1/2 inhibitor in-licensed from Merck KGaA in February 2021 GTP Cellular membrane • Extensive non-clinical and clinical development work through Phase 2, including a solid tumor trial in Japan and combinations NRAS with other MOAs • Main AEs typical for all in-class allosteric MEK inhibitors (GI, BRAFi BRAF CPK elevation, skin rash, visual disturbances) • Nearly three-fold higher CNS penetration than other MEKi inhibitors (trametinib or selumetinib) MEK MEKi • Pimasertib showed monotherapy clinical activity, including an improvement in median PFS versus dacarbazine in NRAS ERK mutant melanoma Nuclear • Combination with tovorafenib (DAY101) and other targeted Cell growth and membrane therapies may unlock the full value of pimasertib in advanced survival Gene transcription solid tumors Source: Hepner, Salgues, Anjos, et al. 2017. Sources: Pimasertib Investigator Brochure, v12, 2019; de Gooijer et al., Int J Cancer, 2018; Shaw et al., Day One Biopharmaceuticals 23 AACR LB-456, 2012; Lebbe et al., Cancers, 2020.
Vertical MAPK Pathway Inhibition with Tovorafenib (DAY101) and Pimasertib May Unlock Potential Synergy for Adult Solid Tumors A B • The MAPK pathway normally has multiple feedback loops that negatively regulate upstream (RAS/RAF) activation to ensure optimal signaling • Monotherapy MEK inhibition disables these feedback loops and induces RAS signaling as well as RAF dimerization and activation Modified from Yen et al. Cancer Cell, 2018 • Combination therapy with a MEK inhibitor and type II RAF inhibitor C Mechanistic model for vertical MAPK pathway inhibition (modified from Yen et al. A is synergistic in KRASmut and Cancer Cell, 2018) . BRAFmut tumor models DAY101 + MEK inhibitor is synergistic in KRAS G12C and Q61 mutant tumor cell B models (Day One internal data) Sensitivity of KRAS Q61 mutant cells to pimasertib is enhanced when cells are C treated with the type II RAF inhibitor BGB-283 (Yuan et al., Mol Onc 2020) Day One Biopharmaceuticals 24
Tovorafenib (DAY101) / Pimasertib Combination to be Evaluated in Solid Tumors (FIRELIGHT-1) 1 Trial Design Endpoints 2 • Combination dose escalation, global phase 1b/2 trial • Phase 1b: PK, PD and Safety, MTD/RP2D • Phase 1b, BOIN (adaptive), n = 10/cohort (approximately) • Phase 2: Efficacy (ORR, DOR) • Phase 2, Simon 2-stage, n = 25/cohort (approximately) • Eligibility: Patients aged 12 years and older, dose escalation will be performed in advanced solid tumor patients with any MAPK alteration. Expansion cohorts will focus on indications with a potential path to accelerated approval Phase 1b Phase 2* NRASmut Selected tumors Tumors with MAPK pathway BRAF Class 1 (non-E/K) and Safety 3 DAY101 + Pimasertib until disease progression alterations Class 2 mutant tumors Follow Up BRAF wt fusion selected tumors Pre-identified patients with advanced solid *Additional biomarker-selected cohorts may tumors and available clinical molecular be pursued based on developing data profiling information. Abbreviations: BOIN, Bayesian Optimal Interval Design; BRAF, B-Raf proto-oncogene, serine/threonine kinase; MAPK, mitogen-activated protein kinase; NRAS, neuroblastoma rat sarcoma viral oncogene. 1. Umbrella master study – DAY101-102 (main protocol) DAY101 and MAPK pathway aberration, Sub-study 1 monotherapy (DAY101-102a), Sub-study 2 MEK combo (DAY101-102b). 3 2. Intend to open U.S. and ex-U.S. clinical sties. DAY101 + Pimasertib until disease progression, intolerable toxicity, withdrawal of consent, or death Day One Biopharmaceuticals 25
Summary Day One Biopharmaceuticals 26
Financial Summary: DAWN Cash, cash equivalents and short-term investments as of 73.5 million shares of common stock September 30, 2022: $374.3 million (no debt) outstanding as of November 2, 2022 Nine Months Ended Nine Months Ended $ Millions 9/30/22 9/30/21 R&D Expense $59.6 $32.4 G&A Expense $44.6 $18.4 Net Loss $102.1 $50.8 FIREFLY-1: Pivotal Phase 2 clinical trial of tovorafenib (DAY101) • Topline results presented in January 2023 Projected • Pre-NDA meeting and NDA submission planned in 1H 2023 cash runway • NDA data set will include additional follow up with data to be presented at a medical meeting in Q2 2023 into 2025 FIREFLY-2/LOGGIC: Pivotal Phase 3 clinical trial of tovorafenib (DAY101) in newly diagnosed pLGG • First patient dosing expected in Q1 2023 All financial and share information is unaudited Day One Biopharmaceuticals 27
Next Steps FIREFLY-1 • Present NDA data set at medical meeting in Q2 2023 • Pre-NDA meeting and NDA submission planned for 1H 2023 FIREFLY-2 Topline data from pivotal Phase 2 FIREFLY-1 trial • Advance tovorafenib as a front-line therapy for patients newly diagnosed with demonstrating meaningful responses with pLGG tovorafenib in recurrent or progressive pLGG Overall response rate of 64% and clinical benefit FIRELIGHT-1 rate of 91% in 69 heavily-pretreated, RANO- • Evaluate tovorafenib in combination and as monotherapy in adolescent and evaluable patients adult populations Median duration of 8.4 months on therapy as of data cut, with 77% of patients remaining on treatment Commercial Safety data, based on the 77 treated patients, • Continue investment in market and launch preparation activities indicated monotherapy tovorafenib to be generally well-tolerated Business Development • Further investment in business development activities to expand our multiple asset portfolio Data cut off as of September 28, 2022. Overall response rate of 64% in 69 heavily-pretreated, RANO-evaluable patients includes confirmed and unconfirmed CR and PR. Clinical benefit rate Day One Biopharmaceuticals 28 (complete response + partial response/unconfirmed partial response + stable disease)
Appendix Day One Biopharmaceuticals 29
FIREFLY-1 Baseline Characteristics Location (n=25) Characteristic Arm 1 (N=25) Deep midline structures Hypothalamus 12% Median age, years (range) 8 (3-18) 8% Sex, n (%) Other Male 13 (52) 16% Female 12 (48) Race, n (%) Optic pathway Cerebellum Black or African American 1 (4) 52% 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 30
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 31
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 32 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 33 -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 AEs Aspartate aminotransferase increased 14 (56) - 12 (48) - 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 34 Day One Biopharmaceuticals
Key Takeaways • Encouraging initial efficacy data from FIREFLY-1 for pediatric patients with recurrent or progressive 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 the Society for Neuro-Oncology (SNO) annual meeting • 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 with a pivotal Phase 3 frontline pLGG study (FIREFLY-2) ‒ Primary endpoint of ORR based on RANO criteria, assessed by blinded independent central review Day One Biopharmaceuticals 35
Case Study: Activity Of Tovorafenib (DAY101) In KIAA1549-BRAF Fusion Optic Pathway Glioma A 7-years-old female child with an optic pathway glioma, with very poor vision, entropion, folliculitis, eczema, mouth ulceration and xerosis Months -36 -30 -24 -18 -12 -6 0 6 PR 1L: Vincristine/carboplatin Diagnostic biopsy 3L: Tovorafenib 2L: Trametinib Best response SD Best response PD • PR (-58%) and improvement in vision reported at cycle 3 • AEs included grade 3 erythematous rash requiring dose interruption and dose reduction (400 mg QW to 300 mg QW in cycle 1), and grade 2 eczema and maculopapular rash • Patient continues to receive weekly tovorafenib Baseline After 6 cycles Tumor kinetics (RANO) Tovorafenib Apr 14, 2022 data cutoff. Tovorafenib is an investigational agent. Safety and efficacy have not 36 been established by any health authority. Day One Biopharmaceuticals
Case Study: Activity Of Tovorafenib (DAY101) In KIAA1549-BRAF Fusion Posterior Fossa Pilocytic Astrocytoma An 8-years-old female child with a posterior fossa pilocytic astrocytoma, eczema, nausea and constipation Months -84 -72 -60 -48 -36 -24 -12 0 12 PR Suboccipital 2L: Carboplatin/vincristine 4L: Trametinib craniotomies 5L: Tovorafenib Best response PR Best response SD 1L: Carboplatin 3L: Vinblastine Best response PD Best response SD • PR (-69%) at cycle 3 with 500 mg QW tovorafenib, with a deepening of response (80% and 91% in cycles 6 and 9, respectively) over time • AEs included grade 2 decrease in neutrophil count, pustular rash, and upper respiratory infection • Patient continues to receive weekly tovorafenib Baseline After 3 cycles After 6 cycles After 9 cycles Tumor kinetics Tovorafenib Apr 14, 2022 data cutoff. Tovorafenib is an investigational agent. Safety and efficacy have 37 not been established by any health authority. Day One Biopharmaceuticals
Case Study: Activity Of Tovorafenib (DAY101) In BRAF V600E Mutation Deep Midline Astrocytoma A 9-year-old female child with deep midline BRAF V600E-mutant astrocytoma with precocious puberty -60 -48 -36 -24 -12 0 Months 12 PR Subtotal 1L: Carboplatin/vincristine 2L: Dabrafenib 3L: Tovorafenib resection Best response PR Best response PR • PR (-74%) at cycle 3, with a deepening of response (-94%) at cycle 6 • AEs included grade 3 maculopapular rash and increased CPK, requiring drug interruption and dose reduction (500 mg QW to 400 mg QW in cycle 1) • Tovorafenib dose was re-escalated back to 500 mg QW in cycle 4; patient continues on treatment Baseline After 3 cycles After 6 cycles Tumor kinetics Tovorafenib Apr 14, 2022 data cutoff. Tovorafenib is an investigational agent. Safety and efficacy have 38 not been established by any health authority. Day One Biopharmaceuticals
Results from Independent Radiology Review of PNOC014 Best response from baseline RANO: Response assessment for neuro- oncology (FDA standard) Volumetric image analysis (exploratory) RAPNO: Response assessment for pediatric neuro-oncology (exploratory) Date of data cutoff: 02 JAN 2020 Day One Biopharmaceuticals 39 Wright K et. al. Neuro Oncology Abstract CTNI-19. 2020
Multiple Rapid, Deep and Durable Responses Observed following Initiation of Tovorafenib (DAY101) Treatment of pLGG Patients in PNOC014 Date of data cutoff: 02 JAN 2020 Adapted from Wright K et. al. Neuro Oncology Abstract CTNI-19. 2020 Day One Biopharmaceuticals 40 Fangusaro J et al. Lancet Oncol 2019
Drug-related Adverse Events Observed for Tovorafenib (DAY101) in PNOC014 Showed Favorable Safety and Tolerability Profile in pLGG Drug-related AEs for Tovorafenib (DAY101) Drug-related AEs for selumetinib Toxicities Grade 1-2 Grade 3 Grade 4 Toxicities Grade 1-2 Grade 3 Grade 4 Anemia 6 (67%) Increased ALT 20 (40%) 1 (2%) Hypophosphatemia 4 (44%) CPK elevation 34 (68%) 5 (10%) Fatigue 5 (55%) Diarrhea 27 (54%) 2 (4%) DAY101 AE summary Rash 8 (89%) Decreased ejection fraction 19 (38%) 1 (2%) • Most common toxicity: skin Achromotrichia 7 (78%) Gastric haemorrhage 1 (2%) Pruritis 6 (67%) • AEs reversible and all Headache 14 (28%) 1 (2%) manageable Photosensitivity 1 (11%) Decreased lymphocyte count 19 (38%) 1 (2%) • Single, reversible Grade 3 Nevus 7 (78%) Neutropenia 14 (28%) 3 (6%) event Alopecia 3 (34%) Paronychia 19 (38%) 3 (6%) • No Grade 4 AEs Epistaxis 2 (22%) Rash (acneiform) 29 (58%) 2 (4%) • No dose reductions (vs. 40% Dry skin 3 (34%) Rash (maculopapular) 26 (52%) 5 (10%) of patients on selumetinib montherapy required dose Myalgias/arthralgias 3 (34%) Skin infection 7 (14%) 1 (2%) reductions) Anorexia 2 (22%) Tooth infection 1 (2%) Cheilitis 3 (34%) Weight gain 5 (10%) 1 (2%) Hypermagnesemia 1 (11%) Vomiting 22 (44%) Bleeding gums 1 (11%) Nausea 21 (42%) Increased AST 4 (44%) Increased AST 25 (50%) Nausea/vomiting 3 (33%) Anemia 28 (56%) CPK elevation 1 (11%) Pruritis 10 (20%) Weight loss 2 (22%) Dyspnea 30 (60%) Date of DAY101 data cutoff: 02 JAN 2020; Wright K et. al. Neuro Oncology Abstract CTNI-19. Day One Biopharmaceuticals 41 2020; Fangusaro J et al. Lancet Oncol 2019