UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): |
(Exact name of Registrant as Specified in Its Charter)
(State or Other Jurisdiction |
(Commission File Number) |
(IRS Employer |
||
|
|
|
|
|
|
||||
|
||||
(Address of Principal Executive Offices) |
|
(Zip Code) |
||
Registrant’s Telephone Number, Including Area Code: |
|
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Securities registered pursuant to Section 12(b) of the Act:
|
|
Trading |
|
|
|
|
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 2.02 Results of Operations and Financial Condition.
On February 26, 2024, Day One Biopharmaceuticals, Inc. issued a press release announcing its financial results for the quarter and year ended December 31, 2023. A copy of the press release is attached as Exhibit 99.1 to this report.
Item 7.01 Regulation FD Disclosure.
On February 26, 2024, Day One Biopharmaceuticals, Inc. updated its corporate presentation. A copy of the updated presentation is attached as Exhibit 99.2 to this report.
The information in this Current Report on Form 8-K, including Exhibit 99.1 and Exhibit 99.2 to this report, shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended (the “Securities Act”). The information contained in this Current Report on Form 8-K and in the accompanying Exhibit 99.1 and Exhibit 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 9.01 Financial Statements and Exhibits.
(d) |
Exhibits |
|
|
|
Exhibit Number |
|
Description |
|
|
|
99.1 |
|
|
|
|
|
99.2 |
|
|
|
|
|
104 |
|
Cover Page Interactive Data File (embedded within the Inline XBRL document). |
SIGNATURES
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 thereunto duly authorized.
|
|
|
DAY ONE BIOPHARMACEUTICALS, INC. |
|
|
|
|
Date: |
February 26, 2024 |
By: |
/s/ Charles N. York II, M.B.A. |
|
|
|
Charles N. York II, M.B.A. |
Exhibit 99.1
Day One Reports Fourth Quarter and Full Year 2023 Financial Results and Corporate Progress
PDUFA target action date for tovorafenib NDA in relapsed or progressive pLGG remains set for April 30, 2024
Phase 2 FIREFLY-1 tovorafenib registrational data published in Nature Medicine
Ended 2023 with $366.3 million in cash, cash equivalents and short-term investments providing runway into 2026
BRISBANE, Calif., Feb. 26, 2024 – Day One Biopharmaceuticals (Nasdaq: DAWN) (“Day One” or the “Company”), a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, today announced its fourth quarter and full year 2023 financial results and highlighted recent corporate achievements.
“We have a monumental year ahead of us at Day One with the upcoming PDUFA date for tovorafenib,” said Jeremy Bender, Ph.D., chief executive officer of Day One. “Our team is trained and ready to deliver our first expected commercial medicine to children in need of new treatment options. We also continue to advance our Phase 3 front-line trial with tovorafenib and are actively exploring other potential additions to our pipeline for children and adults living with cancer.”
Program Highlights
Corporate Highlights and Upcoming Milestones
Fourth Quarter and Full Year 2023 Financial Highlights
Upcoming Events
About Tovorafenib
Tovorafenib is an investigational, oral, brain-penetrant, highly selective type II 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 is currently under evaluation in two pivotal clinical trials for pLGG. Tovorafenib is also being evaluated 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 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 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 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, is an investigational, oral, brain-penetrant, highly selective type II 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 Brisbane, California. For more information, please visit www.dayonebio.com or find the Company on LinkedIn or X.
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 trials for tovorafenib as designed, any expectations about safety, efficacy, timing and ability to complete clinical trials, release data results, the ability of Day One to obtain regulatory approvals for and to commercialize 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 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 global business or macroeconomic conditions, including as a result of inflation, changing interest rates, potential instability in the global banking system, uncertainty with respect to the federal debt ceiling and budget and potential government shutdowns related thereto and global regional conflicts 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.
Day One Biopharmaceuticals, Inc.
Consolidated Statements of Operations
(unaudited)
(in thousands, except shares)
|
|
Year Ended December 31, |
||||
|
|
2023 |
|
2022 |
|
2021 |
Operating expenses: |
|
|
|
|
|
|
Research and development |
|
$ 130,521 |
|
$ 85,618 |
|
$ 43,584 |
General and administrative |
|
75,543 |
|
61,291 |
|
29,159 |
Total operating expenses |
|
206,064 |
|
146,909 |
|
72,743 |
Loss from operations |
|
(206,064) |
|
(146,909) |
|
(72,743) |
Investment income, net |
|
17,187 |
|
4,746 |
|
4 |
Other expense, net |
|
(40) |
|
(18) |
|
(15) |
Net loss |
|
(188,917) |
|
(142,181) |
|
(72,754) |
Net loss attributable to redeemable convertible noncontrolling interest |
|
— |
|
— |
|
(2,109) |
Exchange of redeemable noncontrolling interest shares – deemed dividend |
|
— |
|
— |
|
(99,994) |
Net loss attributable to common stockholders/members |
|
$ (188,917) |
|
$ (142,181) |
|
$ (170,639) |
Net loss per share, basic and diluted |
|
$ (2.37) |
|
$ (2.17) |
|
$ (4.62) |
Weighted-average number of common shares used in computing net loss per share, basic and diluted |
|
79,773,004 |
|
65,466,773 |
|
36,960,569 |
Day One Biopharmaceuticals, Inc.
Selected Consolidated Balance Sheet Data
(unaudited)
(in thousands)
|
|
December 31, |
|
December 31, |
Cash, cash equivalents and short-term investments |
|
$ 366,347 |
|
$ 342,269 |
Total assets |
|
376,048 |
|
349,062 |
Total liabilities |
|
29,508 |
|
17,023 |
Accumulated deficit |
|
(458,585) |
|
(269,668) |
Total stockholders’ equity |
|
346,540 |
|
332,039 |
DAY ONE MEDIA
Laura Cooper, Head of Communications
media@dayonebio.com
DAY ONE INVESTORS
LifeSci Advisors, PJ Kelleher
pkelleher@lifesciadvisors.com
#####
Day One Biopharmaceuticals Targeted Therapies for People of All Ages February 2024
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 short-term investments to fund our operations, business plans and objectives, timing and success of our planned nonclinical and clinical development activities, the results of any of our strategic collaborations, including the potential achievement of milestones and provision of royalty payments thereunder, timing and results of nonclinical studies and clinical trials, efficacy and safety profiles of our product candidates, execution of the Phase 2 and Phase 3 clinical trials 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 inflation, changing interest rates, potential instability in the global banking system, uncertainty with respect to the federal debt ceiling and budget and potential government shutdowns related thereto and global regional conflicts, 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.
Cancer Therapies for People of All Ages Develop medicines for genomically-defined cancers Establish first-in-class position through rapid registration pathways Expand to adolescent and adult populations in parallel and pursue those opportunities with the same commitment we do for children Our Approach Nasdaq: DAWN IPO: 2021 Founded: 2018 Financial Position: Runway into 2026
* FIREFLY-1 Arm 1 expected to support registration. † Pimasertib Phase 1 dose escalation and expansion trial previously completed. † † Includes patients ≥12 years of age. § Research collaboration and license agreement with Sprint Bioscience AB for exclusive worldwide rights to a research-stage program targeting VRK1. pLGG, pediatric low-grade glioma. Tovorafenib and Pimasertib are investigational products. Safety and efficacy have not been established by any health authority. Our Pipeline Product Candidate Indication Preclinical Phase 1 Phase 2 Phase 3 Recent & Anticipated Milestones Tovorafenib (DAY101) Type II RAF Inhibitor FDA Breakthrough Therapy Designation for relapsed pLGG FDA Rare Pediatric Disease Designation (PRV Eligible) for pLGG FDA Orphan Drug Designation for malignant glioma EC Orphan Designation for glioma BRAF-altered Relapsed pLGG FDA acceptance of NDA: October 2023 PDUFA target action date: April 30, 2024 Data published in Nature Medicine: November 2023 Frontline RAF-altered pLGG First patient dosed: March 2023 Pimasertib MEK 1/2 Inhibitor MAPK-altered solid tumors† (Combo w/ tovorafenib) Recommended Phase 2 dose & schedule expected: 2H 2024 VRK1 Program§ VRK1 Inhibitor Pediatric and adult cancers In-licensed: August 2023 FIREFLY-1* (pivotal) FIREFLY-2 (pivotal) FIREFLIGHT-1 † †
Tovorafenib (DAY101) Type II RAF Inhibitor
Sawyer, lives with pLGG. 1 Figures come from FIREFLY-1 baseline patient characteristics with a June 5, 2023 data cutoff. Total patients enrolled in arm 1 of the FIREFLY-1 trial was 77. Kids like Sawyer spend most of their childhood as patients rather than children 3 (1-9) 51% Median (range) number of lines of prior systemic therapy 1 Percentage of patients who had greater than or equal to 3 lines of prior systemic therapy 1
Pediatric Low-Grade Glioma (pLGG): The Most Common Type Of Brain Tumor In Children A Serious and Life-Threatening Disease pLGGs are chronic and relentless, with patients suffering profound tumor and treatment-associated morbidity that can impact their life trajectory over the long term9 1 CBTRUS, Qaddoumi et al 2009, Schreck et al 2019, ClearView Analysis; 2 SEER US complete prevalence counts of patients aged under 25 with Brain and Other Nervous Systems tumors as of January 1, 2017. Estimated prevalence are Day One calculations based on publicly available data. 3 Ostrum QT et al., Neuro Oncol. 2015; 16(Suppl 10):x1-x36; 4 De Blank P. et al., Curr Opin Pediatr. 2019 Feb; 31(1):21-27. 5 Chen Y-H, Gutmann DH. Oncogene. 2014;33(16):2019-2026. 6 Packer RJ et al. Neuro Oncol. 2017;19(6)750-761. 7 Ryall S, et al. Cancer Cell. 2020;37(4):569-583. 8 Ryall S, Tabori U, Hawkins C Acta Neuropathol Commun. 2020;8(1):30. 9 Traunwieser T et al., Neurooncol Adv. 2020; 2:vdaa094. 10 Sievert AJ, Fisher MJ. Pediatric low-grade gliomas. J Child Neurol. 2009;24(11):1397-1408. doi:10.1177/0883073809342005. Disease Symptoms10 An estimated 26,000 children/young adults are living with BRAF-altered pLGGs in the U.S. today 1,2 For the majority of patients in the relapsed setting, there is no standard of care and no approved therapies Surgery plays a significant role in treatment, but vast majority of patients require systemic therapy 3,4 ~70% of pLGGs have BRAF alterations, which means ~55% of pLGGs are BRAF fusions and ~15% are BRAF V600E mutations5-8 Cerebral gliomas: Seizures, muscle weakness, behavioral changes Hypothalamic gliomas: Endocrine dysfunction and visual deficits Optic pathway gliomas: Decreased vision (acuity and/or fields), bulging or misalignment of eyes Cerebellar gliomas: Impaired balance, coordination or depth perception Brain stem gliomas: Difficulty swallowing or with speech, abnormal breathing
Source: 1. Heitzer AM, Raghubar K, Ris MD, et al. Neuropsychological functioning following surgery for pediatric low-grade glioma: a prospective longitudinal study. J Neurosurg Pediatr. 2019;1-9. doi:10.3171/2019.9.PEDS19357. 2. Bryant R. Managing side effects of childhood cancer treatment. J Pediatr Nurs. 2003;18(2):113-125. doi:10.1053/jpdn.2003.11. 3. Zahnreich S, Schmidberger H. Childhood cancer: occurrence, treatment and risk of second primary malignancies. Cancers (Basel). 2021;13(11):2607. doi:10.3390/cancers/13112607. 4. National Cancer Institute. Fertility issues in girls and women with cancer. http://www.cancer.gov. Accessed June 13, 2022. 5. Alessi I., Caroleo A.M., de Palma L., Mastronuzzi A., Pro S., Colafati G.S., Boni A., Della Vecchia N., Velardi M., Evangelisti M., et al. Short and Long-Term Toxicity in Pediatric Cancer Treatment: Central Nervous System Damage. Cancers. 2022;14:1540. doi: 10.3390/cancers14061540. Conventional Treatments Can Be Disruptive To Childhood and Can Have Significant Long-Term Consequences Clear need for an effective therapy for the majority of pLGG relapsed or progressive patients that is minimally disruptive to their lives. Significant recovery times Risks of complications Resection may be limited by location of tumor Potential for functional deficits based on location of tumor and extent of resection Risk of secondary malignancy Risk of malignant transformation Risk of vascular proliferation and stroke Neurocognitive impact, depending on location of tumor and radiation field Requirement for indwelling catheter and weekly infusions Risk of neutropenia, hypersensitivity reactions, nausea and vomiting and peripheral neuropathy Surgery Chemotherapy Radiation
Tovorafenib (DAY101) Inhibits Both BRAF Fusions And BRAF V600 Mutations Tovorafenib (DAY101) is an investigational, oral, selective, CNS-penetrant, type II RAF inhibitor that was designed to inhibit both monomeric and dimeric RAF kinase Activity in tumors driven by both RAF fusions and BRAF V600E mutations Tablet and pediatric-friendly liquid suspension Once weekly dosing Currently approved type I BRAF inhibitors are indicated for use in patients with tumors bearing BRAF V600E mutations Type I BRAF inhibitors cause paradoxical MAPK activation in the setting of wild-type RAF, increasing the risk of tumor growth in BRAF fusion-driven Source: 1. Sun Y et al., Neuro Oncol. 2017; 19: 774–85; 2. Sievart AJ et al., PNAS. 2013; 110:5957-62; 3. Karajannis MA et al., Neuro Oncol 2014;16(10):1408-16. RAS-independent activation of the MAPK pathway MAPK pathway RAS RAF MEK ERK Proliferation and survival RAF mutation RAF fusion Proliferation and survival Proliferation and survival Tovorafenib
June 5, 2023 data cutoff. 1 Wen PY, et al. J Clin Oncol. 2010;28(11):1963-1972. 2 Fangusaro J, et al. Lancet Oncol. 2020;21(6):e305–316. 3 van den Bent MJ, et al. Lancet Oncol. 2011;12(6):583-593. Abbreviations: CBR, clinical benefit rate; IRC, independent review committee; C, cycle; D, day; LGG, low-grade glioma; ORR, objective response rate; PFS, progression-free survival; DoR, duration of response; QW, once weekly; TTR, time to response; RANO, Response Assessment in Neuro-Oncology; RAPNO, Response Assessment in Pediatric Neuro-Oncology; MAPK, mitogen-activated protein kinase. For more information, please refer to NCT04775485 Pivotal Phase 2 Trial Of Monotherapy Tovorafenib (DAY101) In Relapsed Or Progressive pLGG (FIREFLY-1) – Fully Enrolled & Data Accepted by FDA Trial Design Endpoints (Pivotal Arm 1) Three arm, open-label, global registrational phase 2 trial Pivotal Arm 1 (recurrent/progressive pLGG, n=77): harboring a KIAA1549-BRAF fusion or BRAF V600E mutation Arm 2 (expanded access recurrent/progressive LGG, n=60): harboring an activating RAF alteration Arm 3 (extracranial solid tumors): harboring an activating RAF fusion Primary endpoint: ORR based on RANO-HGG1, assessed by blinded independent central review Secondary endpoints: ORR by RAPNO-LGG2 assessed by blinded independent central review; PFS, DoR; TTR, CBR; safety Exploratory analyses: ORR and CBR by RANO-LGG3 assessed by blinded independent central review Day –28 to 0 Study Drug Administration 420mg/m2 QW (not to exceed 600mg), QW in 28-day cycles After Cycle 27: patients may either continue treatment or enter drug holiday period at any time (at discretion of investigator) Screening C27D1 Enrollment/ Baseline (C1D1) End of Trial Clinical and radiological evaluations at baseline, and every 3rd cycle for pLGG and every 2nd cycle for solid tumors Eligibility evaluation Treatment period: minimum of 2 years or until progression or toxicity/intolerability Key Inclusion Criteria 6 months – 25 years of age RAF-altered tumor ≥1 prior line of systemic therapy with radiographic progression Prior use of MAPK pathway targeted therapy was permitted
Data from Pivotal Phase 2 FIREFLY-1 Trial June 5, 2023 data cutoff
FIREFLY-1 Baseline Patient Characteristics June 5, 2023 data cutoff. *Includes 6 patients with BRAF duplication and 2 with BRAF rearrangement per fluorescence in situ hybridization or in situ hybridization. †Includes tumors that were extending into multiple regions of the brain, leptomeningeal disease, and/or spinal disease. ‡The 5 patients that had previously received both a MEK inhibitor and also a BRAF inhibitor are recorded in both the “Prior MEK inhibitor” and “Prior BRAF inhibitor” groups. MAPK, mitogen-activated protein kinase. Characteristic Arm 1 (n=77) Median age, years (range) 8 (2-21) Sex, n (%) Male Female 40 (52) 37 (48) Race, n (%) White Asian Black Multiple Other Not specified 41 (53) 5 (6) 2 (3) 3 (4) 6 (8) 20 (26) Number of lines of prior systemic therapy Median (range) 1, n (%) 2, n (%) ≥3, n (%) 3 (1-9) 17 (22) 21 (27) 39 (51) Prior MAPK pathway targeted therapy, n (%) Prior MEK inhibitor Prior BRAF inhibitor Prior BRAF and MEK inhibitors‡ Any MAPK inhibitor 43 (56) 8* (10) 5 (7) 46 (60) BRAF alteration (n=77) Location (n=77) Optic pathway 51% Cerebral hemisphere 8% Brain stem 8% Deep midline structures 12% Other 16%† Cerebellum 6% 17% 83%
Tumor Response To Tovorafenib (DAY101) Using RAPNO-LGG, RANO-LGG and RANO-HGG Maximum change in tumor size (%) Maximum change in tumor size (%) Maximum change in tumor size (%) RAPNO-LGG RANO-LGG RANO-HGG June 5, 2023 data cutoff. BOR, best overall response; CBR, clinical benefit rate; CI, confidence interval; CR, complete response; DOR, duration of response; HGG, high-grade glioma; IRC, independent radiology review committee; LGG, low-grade glioma; MR, minor response; n/a, not applicable; NE, not evaluable; NR, not reached; ORR, overall response rate; PD, progressive disease; PR, partial response; RANO, Response Assessment in Neuro-Oncology; RAPNO, Response Assessment in Pediatric Neuro-Oncology; SD, stable disease; TTR, time to response. * ORR, CBR and BOR for RAPNO-LGG and RANO-LGG included MRs. Response (IRC) RAPNO-LGG n=76 RANO-LGG N=76 RANO-HGG N=69 ORR,* n (%) 95% CI 39 (51) 40-63 40 (53) 41-64 46 (67) 54-78 CBR,* n (%) SD of any length of time SD ≥12 months 62 (82) 43 (57) 63 (83) 46 (61) 64 (93) 54 (78) BOR,* n (%) CR PR MR SD SD <12 months SD ≥12 months PD NE 0 28 (37) 11 (14) 23 (30) 19 (25) 4 (5) 13 (17) 1 (1) 0 20 (26) 20 (26) 23 (30) 17 (22) 6 (8) 11 (14) 2 (3) 12 (17) 34 (49) n/a 18 (26) 10 (14) 8 (12) 4 (6) 1 (1) Median DOR, months 95% CI 13.8 11.3-NR 14.4 11.0-NR 16.6 11.6-NR Median TTR, months Range 5.3 1.6-11.2 5.5 1.6-11.3 3.0 2.6-16.6
Duration Of Tovorafenib (DAY101) Therapy For All Patients With RAPNO-LGG Evaluable Lesions June 5, 2023 data cutoff. Patients Overall treatment duration (months) 5.3 Months 13.8 Months Median time to response Median duration of treatment
Tumor Kinetics In Patients With Best Response Of Progressive Disease According To RAPNO-LGG June 5, 2023 data cutoff. Change in tumor size (%) Months The majority of patients who had radiographic progression by RAPNO-LGG at their initial disease assessment had subsequent prolonged reductions in the size of their tumor with continued treatment.
Tumor Response To Tovorafenib (DAY101) According To RAPNO-LGG In Subgroups Defined By Baseline Characteristics June 5, 2023 data cutoff. Other races included Asian (n=5), Black (n=2), Multiple (n=3),and Other (n=6). There were no Native Hawaiian or other Pacific Islander or American Indian or Alaska Native. No race information was missing. Ex, External to; US, United States. Analysis of response data across various subgroups shows no significant differences in response rate by RAPNO-LGG. Overall response rate, % (95% confidence interval)
Tumor Response To Tovorafenib (DAY101) Across Three Assessment Criteria Were Consistent Across BRAF Fusion And Mutation Patients, and Patients With Prior MAPK Treatment June 5, 2023 data cutoff. 1 Fangusaro J, et al. Lancet Oncol. 2020;21(6):e305–316. 2 Fangusaro J, et al. Lancet Oncol. 2020;21(6):e305–316. 3 van den Bent MJ, et al. Lancet Oncol. 2011;12(6):583-593. 4. Wen PY, et al. J. Clin Oncol. 2017;35(21),2439-2449. * ORR, CBR for RAPNO-LGG and RANO-LGG included MRs. ** the 95% CI were calculated using Kaplan-Meier method. RAPNO-LGG2 RANO-LGG3,4 RANO-HGG1 Response (IRC) n n n ORR,* n (%) 76 39 (51) 76 40 (53) 69 46 (67) BRAF fusion 64 33 (52) 64 33 (52) 59 41 (69) BRAF mutation 12 6 (50) 12 7 (58) 10 5 (50) Prior MAPKi 45 22 (49) 45 23 (51) 41 29 (71) MAPKi-naive 31 17 (55) 31 17 (55) 28 17 (61) CBR,* n (%) (SD of any length of time) 76 62 (82) 76 63 (83) 69 64 (93) BRAF fusion 64 53 (83) 64 53 (83) 59 55 (93) BRAF mutation 12 9 (75) 12 10 (83) 10 9 (90) Prior MAPKi 45 38 (84) 45 38 (84) 41 37 (90) MAPKi-naive 31 24 (77) 31 25 (81) 28 27 (96) CBR,* n (%) (SD ≥12 months) 76 43 (57) 76 46 (61) 69 54 (78) BRAF fusion 64 37 (58) 64 39 (61) 59 49 (83) BRAF mutation 12 6 (50) 12 7 (58) 10 5 (50) Prior MAPKi 45 25 (56) 45 26 (58) 41 33 (80) MAPKi-naive 31 18 (58) 31 20 (65) 28 21 (75) Median DOR, months (95% CI)** 39 13.8 (11.3-NR) 40 14.4 (11.0-NR) 46 16.6 (11.6-NR) BRAF fusion 33 13.8 (11.3-NR) 33 16.3 (11.0-NR) 41 16.8 (11.6-NR) BRAF mutation 6 NR (8.4-NR) 7 12.0 (8.4-NR) 5 15.1 (8.3-NR) Prior MAPKi 22 13.8 (11.3-NR) 23 12.0 (8.5-NR) 29 15.1 (9.0-16.8) MAPKi-naive 17 NR (8.4-NR) 17 16.3 (8.4-NR) 17 NR (11.6-NR)
Tovorafenib (DAY101) Safety Data (n=137) June 5, 2023 data cutoff. Treatment-emergent AEs ≥25% any grade in arms 1 & 2. AE, adverse event; ALT, Alanine transaminase; AST, aspartate aminotransferase; COVID-19, Coronavirus disease 2019; CPK, creatine phosphokinase; LDH, lactate dehydrogenase; RTI, respiratory tract infection; TEAEs, treatment-emergent adverse events; TRAEs, treatment-related adverse events. TEAEs TRAEs Preferred Term, n (%) Any Grade Grade ≥3 Any Grade Grade ≥3 Any AE 137 (100) 86 (63) 134 (98) 58 (42) Hair color changes 104 (76) 0 104 (76) 0 Anemia 81 (59) 15 (11) 67 (49) 14 (10) Elevated CPK 80 (58) 16 (12) 77 (56) 16 (12) Fatigue 76 (55) 6 (4) 60 (44) 6 (4) Vomiting 68 (50) 6 (4) 28 (20) 3 (2) Hypophosphatemia 64 (47) 0 48 (35) 0 Headache 61 (45) 2 (1) 29 (21) 0 Maculo-papular rash 60 (44) 11 (8) 56 (41) 11 (8) Pyrexia 53 (39) 5 (4) 17 (12) 1 (1) Dry skin 49 (36) 0 45 (33) 0 Elevated LDH 48 (35) 0 42 (31) 0 Increased AST 47 (34) 4 (3) 41 (30) 4 (3) Constipation 45 (33) 0 31 (23) 0 Nausea 45 (33) 0 25 (18) 0 Upper RTI 43 (31) 2 (1) 2 (1) 0 Dermatitis acneiform 42 (31) 1 (1) 41 (30) 1 (1) Epistaxis 42 (31) 1 (1) 27 (20) 0 Decreased appetite 39 (28) 5 (4) 28 (20) 4 (3) Paronychia 36 (26) 2 (1) 32 (23) 2 (1) Pruritus 35 (26) 1 (1) 32 (23) 1 (1) COVID-19 34 (25) 0 0 0 The most common reasons for discontinuation were tumor hemorrhage (3 patients) and decrease in growth velocity (2 patients) 33 patients (24%) had TRAEs leading to dose reduction; 50 patients (37%) had TRAEs leading to dose interruption Median duration of dose interruption was 2 weeks 9 patients (7%) had TRAEs leading to discontinuation
1 Selt F, van Tilburg CM, Bison B, et al. Response to trametinib treatment in progressive pediatric low-grade glioma patients. J Neurooncol. 2020;149(3):499-510. doi:10.1007/s11060-020-03640-3. 2 Ryall S, Tabori U, Hawkins C. Pediatric low-grade glioma in the era of molecular diagnostics. Acta Neuropathol Commun. 2020;8(1):30. doi:10.1186/s40478-020-00902-z. 3 SEER US complete prevalence counts of patients aged under 25 with Brain and Other Nervous Systems tumors as of January 1, 2017. 4 CBTRUS, Qaddoumi et al 2009, Schreck et al 2019, ClearView Analysis. 5 US Census. Estimated annual incidence, estimated prevalence, and estimated recurrent/progressive total addressable patient population are Day One calculations based on publicly available data. 6 Source: Internal market research conducted by EpidStrategies, A Division of ToxStrategies, Inc. on behalf of Day One , * The estimated addressable pool of recurrent or progressive pLGG patients is based on progression free survival curves modeled from published literature. Estimated BRAF-Altered pLGG Patient Population In The U.S. The estimated addressable pool of recurrent or progressive pLGG patients is ~2,000-3,0006 per year at steady state* ~26,000 ~2,000-3,000 ~1,100 Recurrent/Progressive Total Addressable Patient Population per Year6 Incidence of Treatment-Eligible Frontline Patients4,5 Prevalence of Systemically-Treated Patients Under 251-5
Preparing for a Successful Launch* * Pending FDA Approval Key Factors Communicate strong clinical profile for tovorafenib without significant disruption to childhood Enable patient access through establishing broad coverage and patient support programs Experienced, fully dedicated field sales force (18 U.S. Account Managers) Positive patient experience, drug profile consisting of once-weekly dosing (oral tablet or liquid formulation) Priorities Drive FIREFLY-1 Trial and Physician Awareness Build momentum with pediatric oncologists at the ~200 U.S. Centers of Excellence Enable unrestricted patient access
Key Takeaways From FIREFLY-1 Data And Next Steps Response rate is clinically meaningful from FIREFLY-1 for pediatric patients with recurrent or progressive LGG harboring BRAF fusions or BRAF V600E mutations (“BRAF-altered”) 67% ORR by RANO-HGG 51% ORR by RAPNO-LGG 53% ORR by RANO-LGG Deepening of responses observed in patients from December 2022 to June 2023 data cutoffs across all three assessment criteria Meaningful duration of response as of data cutoff (median times: 16.6 months with RANO-HGG, 13.8 months with RAPNO-LGG, and 14.4 months with RANO-LGG)* Responses were observed in patients with either BRAF fusion or BRAF V600E mutations Responses seen in a heavily-pretreated population where the majority (60%) of patients progressed on or after one or more prior MAPK inhibitors Safety and tolerability profile indicating monotherapy tovorafenib to be generally well-tolerated FDA Rare Pediatric Disease Designation for pLGG, eligible for Priority Review Voucher June 5, 2023 data cutoff. * RANO-HGG 95% CI: 11.6-NR, RAPNO-LGG 95% CI: 11.3-NR, RANO-LGG 95% CI: 11.0-NR. Next Steps: Priority review granted with PDUFA target action date of April 30, 2024
FIREFLY-2 / LOGGIC Pivotal Phase 3 Trial of Tovorafenib (DAY101) in Frontline pLGG
FIREFLY-2/LOGGIC Pivotal Phase 3 Trial Of Tovorafenib (DAY101) In Frontline pLGG Trial Design * COG or SIOPe-LGG regimen. Abbreviations: CHG, chiasmatic, hypothalamic glioma; DoR, duration of response; LGG, low-grade glioma; ORR, objective response rate; QoL, quality of life; QW, once weekly; SoC, standard of care. 1 Primary endpoint of FIREFLY-2 will be ORR by RANO-LGG (2017) following full approval by FDA on March 16, 2023 of dabrafenib with trametinib in pediatric patients with low-grade glioma with a BRAF V600E mutation who require systemic therapy based on a study with the same primary endpoint. Endpoints Randomized, global, registrational Phase 3 trial of monotherapy tovorafenib (DAY101) vs SoC chemotherapy Eligibility: Patients aged 6 months to <25 years with LGG harboring a RAF alteration and requiring first-line systemic therapy Tovorafenib (DAY101) available as tablets and pediatric-friendly liquid suspension Patients who progress after stopping tovorafenib (DAY101) may be re-challenged Patients who progress in the SoC arm during or post-treatment may cross-over to receive tovorafenib Primary endpoint: ORR based on RANO-LGG criteria, assessed by blinded independent central review1 The ORR primary analysis is expected to occur ~12 months after the last patient randomized Key secondary endpoints: PFS and DoR by RANO criteria, ORR by RAPNO criteria Other secondary endpoints: changes in neurological and visual function, safety, and tolerability Key exploratory objectives: QoL and health utilization measures Non-resectable or sub-total resected LGG AND Requiring first-line systemic therapy N ≈ 400 Stratified by Location of tumor Genomic alteration CDKN2A status Infant CHG diagnosis Tovorafenib, 420mg/m2 QW (not to exceed 600 mg) Investigator's choice of vincristine/carboplatin* or vinblastine Long-term follow-up (48 months) 1:1 Randomization
FIRELIGHT-1 Phase 1b/2 Trials Evaluating Tovorafenib (DAY101) as a Combination with Pimasertib
Pimasertib: Investigational Allosteric MEK1/2 Inhibitor With Demonstrated Activity In MAPK-Driven Solid Tumors Pimasertib is an investigational orally-bioavailable, selective, non-competitive MEK1/2 inhibitor in-licensed from Merck KGaA in February 2021 Extensive non-clinical and clinical development work through Phase 2, including a solid tumor trial in Japan and combinations with other MOAs Main AEs typical for all in-class allosteric MEK inhibitors (GI, CPK elevation, skin rash, visual disturbances) Nearly three-fold higher CNS penetration than other MEKi inhibitors (trametinib or selumetinib) Pimasertib showed monotherapy clinical activity, including an improvement in median PFS versus dacarbazine in NRAS mutant melanoma Combination with tovorafenib (DAY101) and other targeted therapies may unlock the full value of pimasertib in advanced solid tumors Sources: Pimasertib Investigator Brochure, v12, 2019; de Gooijer et al., Int J Cancer, 2018; Shaw et al., 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 KRAS or NRAS mutant BRAF non-V600 mutant MEK ERK RAF/ MEK/ERK PI3K/m TOR PI3K/m TOR Proliferation, survival Proliferation, survival Type II RAFi + MEKI Type II RAFi + MEKI Non V600 BRAF dimers are effectively inhibited by type II RAFi , but not type I BRAFi Targeting multiple nodes of MAPK pathway will drive deeper and more durable response Type II RAFi + MEKi is synergistic in BRAF fusion melanoma PDX model ex vivo (internal data) Sensitivity of KRAS Q61 mutant cells to pimasertib is enhanced when cells are treated with the type II BRAF inhibitor BGB-283 (Yuan et al., Mol Onc 2020) Tovorafenib (DAY101) + MEK inhibitor is synergistic in KRAS G12C and Q61 mutant tumor cells (Venetsanakos et al., 2021 AACR poster presentation) A B C
NRASmut Selected tumors Pre-identified patients with advanced solid tumors and available clinical molecular profiling information. Tovorafenib (DAY101) / Pimasertib Combination In Solid Tumors (FIRELIGHT-1) Trial Design1 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. 1Umbrella master study – DAY101-102 (main protocol) DAY101 and MAPK pathway aberration, Sub-study 1 monotherapy (DAY101-102a), Sub-study 2 MEK combo (DAY101-102b).2Intend to open U.S. and ex-U.S. clinical sties. 3DAY101 + Pimasertib until disease progression, intolerable toxicity, withdrawal of consent, or death Endpoints Combination dose escalation, global phase 1b/2 trial2 Phase 1b, BOIN (adaptive), n = 10/cohort (approximately) 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: PK, PD and Safety, MTD/RP2D Phase 2: Efficacy (ORR, DOR) Safety Follow Up DAY101 + Pimasertib until disease progression 3 Phase 1b BRAF-fusion selected tumors Phase 2* *Additional biomarker-selected cohorts may be pursued based on developing data Tumors with MAPK pathway alterations BRAF Class 1 (non-E/K) and Class 2 mutant tumors
Summary
Financial Summary: DAWN All financial and share information is unaudited. 1NDA data set includes analysis of primary (ORR by RANO-HGG) and secondary (ORR by RAPNO, PFS) efficacy endpoints, safety, and exploratory analyses (including ORR by RANO-LGG). PRV, Priority Review Voucher. $ Millions Twelve Months Ended 12/31/23 Twelve Months Ended 12/31/22 R&D Expense $130.5 $85.6 G&A Expense $75.5 $61.3 Net Loss $188.9 $142.2 Cash, cash equivalents and short-term investments as of December 31, 2023: $366.3 million (no debt) ~87.4 million shares of common stock outstanding as of February 21, 2024 Projected Cash Runway into 2026 FIREFLY-1: Pivotal Phase 2 clinical trial of tovorafenib (DAY101) NDA1 in May 2023 FDA acceptance of NDA and priority review granted in October 2023 PDUFA target action date of April 30, 2024 (PRV eligible) Data published in Nature Medicine and oral presentations at SNO in November 2023 FIREFLY-2/LOGGIC: Pivotal Phase 3 clinical trial of tovorafenib (DAY101) in newly diagnosed pLGG First patient dosed in March 2023
2023 Key Accomplishments FIREFLY-1: Relapsed or Progressive pLGG Business Development Financials $366.3 million in cash, cash equivalents and short-term investments as of December 31, 2023 Cash runway into 2026 Research collaboration and license agreement for preclinical program targeting VRK1 in August 2023 NDA initiated in May 2023 Clinical data presented in oral presentation at ASCO in June 2023 FDA acceptance of NDA and priority review granted in October 2023 Data published in Nature Medicine and oral presentation at SNO in November 2023 PDUFA target action date of April 30, 2024 FIREFLY-2: Frontline pLGG Dosed the first patient in March 2023
Priorities as we Expand into a Commercial-Stage Company Secure the first FDA-approved targeted therapy for pLGG with BRAF fusions and point mutations that have relapsed or progressed Expand awareness amongst physicians and establish broad coverage to enable patient access Following approval, establish tovorafenib as the standard of care for relapsed or progressive pLGG Grow Day One into a leading, biopharmaceutical company that is the partner of choice for oncology drug development Explore selective partnerships as a source of capital and risk sharing Further invest in business development activities to expand our multiple asset portfolio for both children and adults FIREFLY-2: Study tovorafenib as a frontline therapy for treatment-naive patients with pLGG FIRELIGHT-1: Evaluate tovorafenib in combination with pimasertib in adolescent and adult populations Advance early stage VRK1 program to clinical development Launch Tovorafenib Advance Portfolio Expand Pipeline
Appendix
Duration Of Tovorafenib (DAY101) Therapy For All Patients With RANO-HGG Evaluable Lesions Patients Overall treatment duration (months) June 5, 2023 data cutoff. 3.0 Months 16.6 Months Median time to response Median duration of treatment
Duration Of Tovorafenib (DAY101) Therapy For All Patients With RANO-LGG Evaluable Lesions Patients Overall treatment duration (months) June 5, 2023 data cutoff. 5.5 Months 14.4 Months Median time to response Median duration of treatment
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 Apr 14, 2022 data cutoff. Tovorafenib is an investigational agent. Safety and efficacy have not been established by any health authority. Months -36 -30 -24 -18 -12 -6 0 After 6 Cycles Baseline 1L: Vincristine/carboplatin Best response SD Diagnostic biopsy PR 6 2L: Trametinib Best response PD 3L: Tovorafenib Tumor kinetics (RANO) Tovorafenib 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
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 Tovorafenib 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 Apr 14, 2022 data cutoff. Tovorafenib is an investigational agent. Safety and efficacy have not been established by any health authority. Months -84 -72 -60 -48 -36 -24 -12 Baseline 3L: Vinblastine Best response SD PR 0 4L: Trametinib Best response SD 5L: Tovorafenib Tumor kinetics 12 2L: Carboplatin/vincristine Best response PR 1L: Carboplatin Best response PD Suboccipital craniotomies After 3 Cycles After 6 Cycles After 9 Cycles
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 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 Apr 14, 2022 data cutoff. Tovorafenib is an investigational agent. Safety and efficacy have not been established by any health authority. Months -60 -48 -36 -24 -12 Baseline PR 0 2L: Dabrafenib Best response PR 3L: Tovorafenib Tumor kinetics 12 1L: Carboplatin/vincristine Best response PR Subtotal resection After 3 Cycles After 6 Cycles Tovorafenib
Initiated treatment with tovorafenib 400 mg/QW following 3 prior therapies, including binimetinib and trametinib, which were discontinued due to PD At cycle 3, PR (-88%) per RANO-HGG, and MR (-32% and -40%) per RAPNO-LGG and RANO-LGG, respectively Sustained improvements in visual acuity reported; logMAR change 0.2 → 0 PD criteria met (-94% to -91%) with RANO-HGG at cycle 15; continued treatment as investigator deemed no radiographic progression with subsequent reduction in target lesion (-97%) AEs were G2 (drug eruption, elevated CPK) and G1 (hair color change, paronychia, growth retardation) Case Study: Activity Of Tovorafenib (DAY101) In KIAA1549-BRAF Fusion Posterior Fossa Pilocytic Astrocytoma 8-year-old boy with relapsed pilomyxoid astrocytoma of the optic pathway, with visual loss in right eye, visual field loss in left eye, fatigue, intermittent nausea/vomiting, intermittent headaches, anorexia, and temperature regulation disorder Dec 22, 2022, data cut-off. AEs, adverse events; C, contrast; CPK, creatine phosphokinase; G, grade; HGG, high-grade glioma; LGG, low-grade glioma; logMAR, Logarithm of the Minimum Angle of Resolution; MR, minor response; PD, progressive disease; PR, partial response; QW, once weekly; RANO, Response Assessment in Neuro-Oncology; RAPNO, Response Assessment in Pediatric Neuro-Oncology; VC, vincristine-carboplatin.. Months -60 -48 -36 -24 -12 VC Trametinib PR 0 Tovorafenib 12 24 Binimetinib T1 + C (baseline and post cycle 3) T2 (baseline and post cycles 3 & 12) Tumor kinetics
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 ~20 Sites ~65 Sites ~5 Sites ~10 Sites Approximately 100 potential sites (~65 from the LOGGIC consortium)