Day One Biopharmaceuticals : Corporate Presentation - October 2023

Day One Biopharmaceuticals

Targeted Therapies for People of All Ages

October 2023

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, rising interest rates, cybersecurity incidents, instability in the global banking system, government shutdowns, uncertainty with respect to the federal budget and geopolitical conflicts, including the conflicts in Israel and Ukraine, 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.

2

2

Cancer Drug Development For People Of All Ages

A Mission That Creates Value

Nasdaq: DAWN

IPO: 2021

Founded: 2018

Financial	Runway into 2026
Position

• 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

• Lead program FIREFLY-1: FDA acceptance of NDA and priority review granted with PDUFA target action of date of April 30, 2024

Growing	• Frontline trial (FIREFLY-2) underway

Portfolio	• Clinical-stage MEKi asset (pimasertib), in-licensed for combination trial with tovorafenib
	• Research collaboration and license agreement for preclinical program targeting VRK1

3

NDA data set included analysis of primary (ORR by RANO-HGG) and secondary (ORR by RAPNO-LGG, PFS) efficacy endpoints, safety, and exploratory analyses (including ORR by RANO-LGG).

Our Pipeline

Product Candidate	Indication	Preclinical	Phase 1	Phase 2	Phase 3	Recent & Anticipated
Milestones
						Topline data presented:
Tovorafenib (DAY101)						September 2023
Relapsed pLGG	FIREFLY-11 (pivotal)				FDA acceptance of NDA:
Type II RAF Inhibitor				October 2023
						PDUFA target action date:
• FDA Breakthrough Therapy						April 30, 2024
Designation for relapsed pLGG

• FDA Rare Pediatric Disease Designation (PRV Eligible) for pLGG

Frontline pLGG

FIREFLY-2 (pivotal)

First patient dosed: March 2023

• FDA Orphan Drug Designation for malignant glioma
• EC Orphan Designation for glioma

RAF-altered
solid tumors2	FIRELIGHT-1*
(monotherapy)

First patient dosed: November 2021

Poster presented:

April 2023

Pimasertib	MAPK-altered		First patient dosed:
MEK 1/2 Inhibitor	solid tumors3	FIRELIGHT-1*	May 2022
	(Combo w/tovorafenib)
VRK1 Program4	Pediatric and		In-licensed:
VRK1 Inhibitor	adult cancers		August 2023

4

*Includes patients ≥12 years of age. 1 FIREFLY-1 Arm 1 expected to support registration. 2 DAY101 adult monotherapy Phase 1 dose escalation and expansion trial previously completed. 3 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. 4 Research collaboration and license agreement with Sprint Bioscience AB for exclusive worldwide rights to a research-stage program targeting VRK1.

Tovorafenib (DAY101)

Type II RAF Inhibitor

Pediatric Low-Grade Glioma (pLGG): The Most Common Type Of Brain Tumor In Children

PLGGs are chronic and relentless, with patients suffering profound tumor and

treatment-associated morbidity that can impact their life trajectory over the long term6

A Serious and Life-Threatening Disease		Disease Symptoms7

• An estimated 26,000 children/young adults are living with BRAF-altered pLGGs in the U.S. today1,2
• Surgery plays a significant role in treatment, but 70% of patients require systemic therapy3,4
• For the majority of patients in the relapse setting, there is no standard of care and no approved therapies
• ~70% of pLGGs have BRAF alterations, of these ~85% are BRAF fusions and ~15% are BRAF V600E mutations5
• Majority of patients have many years of treatment until the tumors typically senesce by their mid-20s

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

6

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 Jones DTW et al., Cancer Res. 2008; 68:8673-77.6 Traunwieser T et al., Neurooncol Adv. 2020; 2:vdaa094. 7 Sievert AJ, Fisher MJ. Pediatric low-grade gliomas. J Child Neurol. 2009;24(11):1397-1408. doi:10.1177/0883073809342005.

Conventional Treatments Can Be Disruptive To Childhood and Can Have Significant Long-Term Consequences

Surgery

• 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

Chemotherapy

• Requirement for indwelling catheter and weekly infusions
• Risk of neutropenia, hypersensitivity reactions, nausea and vomiting and peripheral neuropathy

Radiation

• Risk of secondary malignancy
• Risk of malignant transformation
• Risk of vascular proliferation and stroke
• Neurocognitive impact, depending on location of tumor and radiation field

7

High unmet need for an effective therapy for the majority of pLGG relapsed or progressive patients

that is minimally disruptive to their lives.

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.

Tovorafenib (DAY101) Inhibits Both BRAF Fusions And BRAF V600 Mutations

MAPK pathway

RAS

RAF

MEK

ERK

Proliferation and survival

RAS-independent activation of the MAPK pathway

RAF		Tovorafenib		RAF fusion
mutation

Proliferation and survival

Proliferation and survival

• 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 BRAFi 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

8

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.

The Current pLGG Treatment Paradigm Reflects The Unrelenting Nature Of This Chronic Brain Tumor

Presentation

Surgical Intervention

1L

2L

3L

~35%

~20%

GTR

No Recurrence

Targeted Tx

Targeted Tx

Targeted Tx

Biopsy1

(5-10%)

(40-50%)

(40-50%)

Suspected

(>95%)

~65%

~50%

~50%

pLGG

≤ Partial

Eventual

Additional lines

Chemo

Chemo

Chemo

~40%

Resection

~80%

Recurrence

of therapy

(~90%)

(~50%)

(~35%)

Molecular

Testing

Biopsy Only

Other

Other

Other

~20%

(<5%)

(<5%)

(<20%)

No Biopsy

(~5%)

Response,

~50%

Response,

~35%

no recurrence

no recurrence

Because many pLGGs undergo senescence when patients reach their 20s, the goal of therapy is to maximize tumor

control while minimizing treatment-associatedtoxicities 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.

9

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

Pivotal Phase 2 Trial Of Monotherapy Tovorafenib (DAY101) In Relapsed Or Progressive pLGG (FIREFLY-1) - Fully Enrolled & Data Submitted to 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

Key Inclusion Criteria	Clinical and radiological evaluations at baseline, and every 3rd
		cycle for pLGG and every 2nd cycle for solid tumors

• 6 months - 25 years of age

•	RAF-altered tumor		Day -28 to 0	Enrollment/
•	≥1 prior line of systemic				End of Trial
Screening	Baseline
	therapy with radiographic			(C1D1)	Study Drug Administration	C27D1	After Cycle 27: patients may either continue
	progression
						420mg/m2 QW (not to exceed 600mg),	treatment or enter drug holiday period at any time
• Prior use of MAPK pathway
					QW in 28-day cycles		(at discretion of investigator)
	targeted therapy was
	permitted
			Eligibility evaluation				Treatment period: minimum of 2 years or until progression or toxicity/intolerability

10

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