UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
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| Item 5.02 | Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers. |
Appointment of New Director
On September 9, 2022, upon the recommendation of the Nominating and Governance Committee (the “Governance Committee”) of the Board of Directors (the “Board”) of Day One Biopharmaceuticals, Inc. (the “Company”), the Board increased the size of the Board to nine directors and appointed Garry Nicholson as a Class I director, effective as of September 12, 2022 (the “Effective Date”). In connection with his appointment to the Board, Mr. Nicholson has been appointed as chairperson of the Board and as a member of the Governance Committee. Julie Papanek Grant, the prior chairperson of the Board, shall continue as a member of the Board.
In connection with his appointment as a non-employee director of the Board, and in accordance with the Company’s current compensation policy for non-employee directors (the “Compensation Policy”), the Board granted Mr. Nicholson a stock option to purchase shares of the Company’s common stock with an aggregate value of $560,000, calculated in accordance with the Compensation Policy (the “Initial Grant”). The Initial Grant shall vest monthly over three years, beginning on the one-month anniversary of the Effective Date, subject, however, to Mr. Nicholson’s continued service on the Board on each vesting date.
Pursuant to the Compensation Policy, on the date of each annual meeting of the Company’s stockholders, each non-employee director who is serving on the Board prior to, and will continue to serve on the Board following, such meeting is entitled to an annual stock option grant for shares of the Company’s common stock with an aggregate value of $280,000 (the “Annual Grant”), calculated in accordance with the Compensation Policy. Mr. Nicholson will be eligible for Annual Grants, provided, that, he satisfies the requirements set forth in the Compensation Policy, including the service requirements.
The Initial Grant and any Annual Grants awarded to Mr. Nicholson will be issued under the Company’s 2021 Equity Incentive Plan and will accelerate in full upon a change of control. Mr. Nicholson will also be entitled to the applicable annual cash retainer paid to non-employee directors under the Compensation Policy.
The Company has entered into its standard form of indemnification agreement with Mr. Nicholson. The form of the indemnification agreement was previously filed by the Company as Exhibit 10.1 to the Company’s registration statement on Form S-1 (File No. 333-255754) filed with the Securities and Exchange Commission on May 26, 2021 and incorporated by reference herein.
There are no arrangements or understandings between Mr. Nicholson and any other persons, pursuant to which Mr. Nicholson was selected as a member of the Board. There are also no family relationships among any of the Company’s other directors or executive officers and Mr. Nicholson. Mr. Nicholson does not have any other direct or indirect material interest in any transaction required to be disclosed pursuant to Item 404(a) of Regulation S-K.
| Item 7.01 | Regulation FD Disclosure. |
On September 12, 2022, the Company issued a press release announcing the appointment disclosed above. A copy of this press release is attached hereto as Exhibit 99.1 and is incorporated by reference herein. Additionally, on September 12, 2022, the Company updated its corporate presentation. A copy of the updated corporate presentation is attached as Exhibit 99.2 and is also available on the Company’s website in the Events & Presentations section at www.dayonebio.com.
The information in this Item 7.01, including Exhibits 99.1 and 99.2 to this report, shall not be deemed to be “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act. The information contained in this Item 7.01 and in the accompanying Exhibits 99.1 and 99.2 shall not be incorporated by reference into any other filing under the Exchange Act or under the Securities Act, except as shall be expressly set forth by specific reference in such filing.
| Item 8.01 | Regulation FD Disclosure. |
On September 12, 2022, the Company updated guidance on the planned first patient dosing to the second half of 2022 for the Company’s Phase 3 clinical trial (FIREFLY-2/LOGGIC) evaluating tovorafenib as a front-line therapy for patients newly diagnosed with pLGG.
| Item 9.01 | Financial Statement and Exhibits. |
(d) Exhibits
| Exhibit Number |
Description | |
| 99.1 | Press release issued by Day One Biopharmaceuticals, Inc. regarding the appointment of a new director, dated September 12, 2022. | |
| 99.2 | Corporate Presentation. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |
Forward-Looking Statements
This Current Report on Form 8-K contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and other federal securities laws. Any statements contained herein that do not describe historical facts, including, but not limited to, statements we make regarding the timing of our Phase 3 clinical trial (FIREFLY-2/LOGGIC). Such risks and uncertainties include, among others, the risks identified in the Company’s filings with the SEC, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2022, filed with the SEC on August 4, 2022, and other reports as filed with the SEC. The Company cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. The Company undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date they were made or to reflect the occurrence of unanticipated events.
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| DAY ONE BIOPHARMACEUTICALS, INC. | ||||||
| Date: September 12, 2022 | By: | /s/ Charles N. York II, M.B.A. | ||||
| Name: | Charles N. York II, M.B.A. | |||||
| Title: | Chief Operating Officer and Chief Financial Officer | |||||
Exhibit 99.1
Day One Appoints Garry Nicholson as Chairman of the Board of Directors
SOUTH SAN FRANCISCO, Calif., September 12, 2022 – 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 the appointment of Garry Nicholson as chairman of its board of directors. Mr. Nicholson brings more than 30 years of pharmaceutical and biotech oncology experience and previously served as president of Pfizer Oncology where he led its global oncology franchise. Day One co-founder Julie Grant, who served as board chair since 2021, will continue to serve as a member of the board of directors.
“Garry is an accomplished leader in the development and commercialization of new cancer therapies and we are thrilled to welcome him as chairman of our board of directors,” said Jeremy Bender, Ph.D., chief executive officer of Day One. “Garry’s expertise and guidance will be critical as tovorafenib continues to advance in our pivotal FIREFLY-1 trial towards potential commercialization for relapsed pediatric low-grade glioma and as our other ongoing clinical trials continue to progress.”
Mr. Nicholson currently serves as chairman of the board of directors for G1 Therapeutics and as a board member for Tmunity Therapeutics and NextCure. He also previously served on the board of directors for Turning Point Therapeutics, Five Prime Therapeutics and TESARO prior to their acquisitions by large pharmaceutical companies. As former president of Pfizer Oncology, his responsibilities included global commercialization, sales, clinical development, regulatory strategy and business development for Pfizer’s oncology portfolio. Earlier in his career, Mr. Nicholson held various leadership positions in the oncology division of Eli Lilly and Company, including global oncology platform leader. He has also served as president and CEO of XTuit Pharmaceuticals. Mr. Nicholson earned a B.S. in Pharmacy from the University of North Carolina at Chapel Hill and an M.B.A. from the University of South Carolina.
“Day One is an innovative company dedicated to advancing new cancer therapies for people of all ages and I could not be more excited to join its board of directors as chairman,” said Mr. Nicholson. “Tovorafenib has the potential to become a meaningful new targeted treatment for pediatric low-grade glioma, a devastating form of childhood brain cancer, and I look forward to applying my oncology market experience as the company prepares for potential commercialization.”
About Tovorafenib
Tovorafenib is an investigational, oral, brain-penetrant, highly selective type II pan-RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway, which is being investigated in primary brain tumors and solid tumors harboring activating RAF alterations. Tovorafenib has been studied in over 325 patients to date. Currently tovorafenib is under evaluation in a pivotal Phase 2 clinical trial (FIREFLY-1) among pediatric, adolescent and young adult patients with relapsed pediatric low-grade glioma (pLGG), which is an area of considerable unmet need with no approved therapies for the majority
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of patients. Day One has also initiated a pivotal Phase 3 study (FIREFLY-2/LOGGIC) in newly-diagnosed patients with pLGG. Beyond pLGG, tovorafenib is 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 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 Company’s name was inspired by the “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 what’s possible for all people living with cancer—regardless of age—starting from Day One.
Day One partners with leading clinical oncologists, families, and scientists to identify, acquire, and develop important emerging cancer treatments. The Company’s lead product candidate, tovorafenib (DAY101), is an investigational, oral, brain-penetrant, highly-selective type II pan-RAF kinase inhibitor. The Company’s 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 One’s plans to develop cancer therapies, expectations from current clinical trials, the execution of the Phase 2 and Phase 3 clinical trial for tovorafenib (DAY101) as designed, any expectations about safety, efficacy, timing and ability to complete clinical trials, release data results and to obtain regulatory approvals for tovorafenib (DAY101) and other candidates in development, and the ability of tovorafenib (DAY101) 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 One’s 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 One’s ability to develop, obtain regulatory approval for or commercialize any product candidate, Day One’s ability to protect intellectual property, the potential impact of the COVID-19 pandemic and the sufficiency of Day One’s 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.
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Contacts:
Media:
1AB
Dan Budwick
dan@1abmedia.com
Investors:
LifeSci Advisors
Hans Vitzthum
hans@lifesciadvisors.com
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Exhibit 99.2 Targeted Therapies for People of All Ages September 2022 June 2022
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 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 and the Phase 1b/2 clinical trial for DAY101 and pimasertib 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 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
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, 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 • 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 through rapid pediatric registration • Orphan Drug Designation (US/EU) • NDA submission in 1H 2023, if • Expand to adolescent and adult data are supportive populations in parallel and pursue those opportunities with the same • First patient dosing in pivotal commitment we do for children Phase 3 (FIREFLY-2 /LOGGIC), frontline trial expected 2H 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 Mike Preigh, PhD Davy Chiodin, PharmD Jaa Roberson Chief Technical Officer Chief Development Officer Chief People Officer Head of CMC at Array for 10+ years. Brought >20 drug VP Regulatory Science, Acerta/AZ; Global Regulatory Head of Human Resources at Bellicum Pharmaceuticals; candidates to IND & clinical development Leader, Pediatric Oncology, Roche/Genentech Human Resources Roles at Achaogen, Roche/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 ü FDA Breakthrough Therapy Designation for relapsed pLGG Trial Initiation: June 2022 FIREFLY-2 (pivotal) Frontline pLGG First patient dosing ü FDA Rare Pediatric Disease expected: 2H 2022 Designation (PRV Eligible) for pLGG ü FDA Orphan Drug Designation for gliomas RAF-altered First patient dosed: ü 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 Biopharmaceuticals 7
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 8
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 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 17
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 Mutated (70%) ~1,100 ~26,000 ~1,100 ~26,000 Estimated Annual Incidence Estimated Prevalence (SEER) 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 (SEER) are prevalence counts of patients aged under 25 with Brain and Other Nervous Systems tumors as of January 1, 2017. Day One calculations based on publicly available data. 18 Day One Biopharmaceuticals
FIREFLY-2/LOGGIC Pivotal Phase 3 Trial of Tovorafenib (DAY101) in Newly Diagnosed pLGG Day One Biopharmaceuticals 19
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 • Key secondary endpoints: PFS and DoR by RANO criteria, ORR by alteration and requiring first-line systemic therapy RAPNO criteria • Tovorafenib (DAY101) available as tablets and pediatric-friendly liquid suspension • Other secondary endpoints: changes in neurological and visual • Patients who progress after stopping tovorafenib (DAY101) may be re-challenged function, safety, and tolerability • Patients who progress in the SoC arm during or post-treatment may cross-over to • Key exploratory objectives: QoL and health utilization measures receive tovorafenib 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 20 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 21
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 ü FDA Breakthrough Therapy Designation for relapsed pLGG Trial Initiation: June 2022 FIREFLY-2 (pivotal) Frontline pLGG First patient dosing ü FDA Rare Pediatric Disease expected: 2H 2022 Designation (PRV Eligible) for pLGG ü FDA Orphan Drug Designation for gliomas RAF-altered First patient dosed: ü 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 22
Tovorafenib (DAY101) is Active as a Monotherapy in Patients with RAF-altered Adult Solid Tumors and Has Shown Strong Synergy Preclinically in Combination • >225 adult patient exposures Clinical activity demonstrated in relapsed melanoma patients; preclinical • Responses in BRAF V600E mutant tumors similar to type I BRAF inhibitors activity demonstrated in RAF fusions, • Responses in relapsed BRAF and NRAS-mutant melanoma, suggesting BRAF non-V600 mutations, and BRAF tovorafenib (DAY101) may be active in tumors currently unaddressed by V600 mutations approved Type I BRAF inhibitors • Less frequent and less severe acneiform rash Differentiated safety profile for • No observed ophthalmologic liabilities (RVO/CSR) tovorafenib (DAY101) vs. existing BRAF • No observed CV liabilities (changes in LVEF) and MEK inhibitors • No type I BRAF SAEs: SCCs/KAs, pyrexia, arthralgia We initiated an adult solid tumor study to further • Same study will include combination cohorts of tovorafenib evaluate monotherapy tovorafenib (DAY101) + pimasertib (DAY101) in patients with RAF altered • First patient dosed in Phase 2 monotherapy study in November 2021 tumors for which there are no currently approved therapies Source: Olszanski AJ et. al. European Society for Medical Oncology Congress; Poster #410P, 2017 Unpublished clinical study results Day One Biopharmaceuticals 23
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 Trametinib 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 24
Next-generation RAF Inhibitors are Unique in Their Ability to Address Adult Cancers Associated with RAF Wild-type Fusions Only 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 25
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 26
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 27
Pimasertib MEK1/2 Inhibitor Day One Biopharmaceuticals 28
Pimasertib: Allosteric MEK1/2 Inhibitor with Demonstrated Activity in MAPK-driven Solid Tumors RTKS GF • Pimasertib is an orally-bioavailable, selective, non-competitive MEK1/2 inhibitor in-licensed from Merck KGaA in February 2021 GTP • Extensive non-clinical and clinical development work through Cellular membrane Phase 2, including a solid tumor trial in Japan and combinations with other MOAs NRAS • Main AEs typical for all in-class allosteric MEK inhibitors (GI, CPK elevation, skin rash, visual disturbances) BRAFi BRAF • 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 mutant melanoma ERK • Combination with tovorafenib (DAY101) and other targeted Nuclear therapies may unlock the full value of pimasertib in advanced Cell growth and membrane solid tumors survival Gene transcription 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 29 AACR LB-456, 2012; Lebbe et al., Cancers, 2020.
Vertical MAPK Pathway Inhibition with Tovorafenib (DAY101) and Pimasertib Unlocks 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 30
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 31
Summary Day One Biopharmaceuticals 32
Financial Summary: DAWN Cash, cash equivalents and short-term investments as 73.5 million shares of common stock Follow-on in June 2022: $172.5 million in gross of June 30, 2022: $394.9 million (no debt) outstanding as of August 1, 2022 proceeds, includes full exercise of underwriters’ option Six Months Ended Six Months Ended $ Millions 6/30/22 6/30/21 R&D Expense $37.6 $22.5 G&A Expense $26.9 $9.0 Net Loss $64.3 $31.6 FIREFLY-1: Pivotal Phase 2 clinical trial of tovorafenib (DAY101) • Pivotal cohort enrollment completed in May 2022 • Initial clinical data presented in June 2022 Projected • Full topline results expected in Q1 2023 • NDA submission planned in 1H 2023, if data from FIREFLY-1 is supportive cash runway FIREFLY-2/LOGGIC: Pivotal Phase 3 clinical trial of tovorafenib (DAY101) in newly diagnosed pLGG into 2025 • Trial initiated in June 2022 • First patient dosing expected in 2H 2022 FIRELIGHT-1: Tovorafenib (DAY101) and pimasertib combination • First patient dosed in May 2022 All financial and share information is unaudited Day One Biopharmaceuticals 33
Appendix Day One Biopharmaceuticals 34
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 35 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 36 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 37 not been established by any health authority. Day One Biopharmaceuticals
FIREFLY-1 Study Status • First patient dosed in May 2021. Registrational pLGG arm completed enrollment in May 2022 • ~35 sites opened across 11 countries • Expanded access to patients with pLGG (arm 2) and RAF fusion-positive solid tumors (arm 3) • Interim efficacy and safety analysis in the first 25 consecutively enrolled patients who had: • Received at least 1 dose of study treatment • At least 6 months of follow-up as of April 14, 2022 • Tumor assessments according to RANO criteria, as determined by a blinded independent radiological review committee • 22 patients with RANO-evaluable tumors Day One Biopharmaceuticals 38
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