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
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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:
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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 May 12, 2022, Day One Biopharmaceuticals, Inc. issued a press release announcing its financial results for the quarter ended March 31, 2022. A copy of the press release is attached as Exhibit 99.1 to this report.
Item 7.01 Regulation FD Disclosure.
On May 12, 2022, 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.
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Description |
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99.1 |
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99.2 |
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104 |
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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.
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DAY ONE BIOPHARMACEUTICALS, INC. |
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Date: |
May 12, 2022 |
By: |
/s/ Charles N. York II, M.B.A. |
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Charles N. York II, M.B.A. |
Exhibit 99.1
Day One Reports First Quarter 2022 Financial Results and Provides Business Update
Initial data from pivotal FIREFLY-1 study with tovorafenib (DAY101) in relapsed pediatric low-grade glioma (pLGG) expected in June 2022
Company plans to initiate pivotal Phase 3 FIREFLY-2 clinical trial evaluating tovorafenib as a first-line therapy in pLGG in the second quarter of 2022
Initiated Phase 1b/2 combination study with tovorafenib and pimasertib in RAF-altered solid tumors
SOUTH SAN FRANCISCO, Calif., May 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 financial results for the first quarter of 2022 and highlighted recent corporate achievements.
“We continue to make excellent progress across our clinical programs and look forward to reporting initial data from our pivotal Phase 2 FIREFLY-1 trial in relapsed pLGG next month,” said Jeremy Bender, Ph.D., chief executive officer of Day One. “These initial data will provide preliminary insights into the potential of tovorafenib to transform patient care for the most common childhood brain cancer, which currently has no approved therapies. Beyond FIREFLY-1, we are preparing to initiate a pivotal Phase 3 study, FIREFLY-2, for the first-line treatment of pLGG patients and recently initiated the combination portion of our Phase 2 FIRELIGHT-1 study with tovorafenib and our investigational oral MEK inhibitor, pimasertib. As our clinical programs advance, we continue to accelerate planning for our first potential regulatory submission for tovorafenib in 2023 and execute on our business strategy to make an impact for patients of all ages with life threatening diseases.”
Program Highlights
First Quarter 2022 Financial Highlights
Upcoming Events
Page 2 of NUMPAGES 6
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 or brain metastases of solid tumors. Tovorafenib has been studied in over 250 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 pediatric low-grade glioma (pLGG), which is an area of considerable unmet need with no approved therapies. Tovorafenib is also being evaluated alone or as a combination therapy for adolescent and adult patient populations with recurrent or progressive solid tumors with MAPK pathway aberrations (FIRELIGHT-1). Tovorafenib has been granted Breakthrough Therapy and Rare Pediatric Disease designations by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pLGG harboring an activating RAF alteration. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma, and from the European Commission (EC) for the treatment of glioma.
About Pimasertib
Pimasertib is an investigational, oral, highly selective, small molecule inhibitor of mitogen‐activated protein kinases 1 and 2 (MEK-1/-2) within the MAPK signaling pathway. Pimasertib has been dosed in over 850 patients to date for various tumor types. Preclinical data indicates that the combination of a MEK inhibitor, such as pimasertib, and a type II RAF inhibitor, such as tovorafenib, has synergistic anti-tumor activity.
Day One is conducting a Phase 1b/2 study (FIRELIGHT-1) to evaluate the safety, tolerability, and preliminary efficacy of combining pimasertib with tovorafenib in adolescent and adult patients (≥12 years of age) with recurrent, progressive, or refractory solid tumors with MAPK pathway aberrations.
About Day One Biopharmaceuticals
Day One Biopharmaceuticals is a clinical-stage biopharmaceutical company developing targeted therapies for patients of all ages with life-threatening diseases. 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 is 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.
Page 3 of NUMPAGES 6
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 clinical trial for DAY101 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, and the ability of 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.
Contacts:
Media:
1AB
Dan Budwick
dan@1abmedia.com
Investors:
LifeSci Advisors
Hans Vitzthum
hans@lifesciadvisors.com
Page 4 of NUMPAGES 6
Day One Biopharmaceuticals, Inc.
Consolidated Statements of Operations and Comprehensive Loss
(unaudited)
(In thousands)
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Three Months Ended |
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2022 |
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2021 |
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Operating expenses: |
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Research and development |
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$ |
15,003 |
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$ |
12,632 |
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General and administrative |
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12,745 |
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3,454 |
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Total operating expenses |
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27,748 |
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16,086 |
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Loss from operations |
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(27,748 |
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(16,086 |
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Interest income (expense), net |
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2 |
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(7 |
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Other expense, net |
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(1 |
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(8 |
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Net loss and comprehensive loss |
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(27,747 |
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(16,101 |
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Net loss attributable to redeemable convertible noncontrolling |
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— |
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(919 |
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Net loss attributable to common stockholders/members |
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$ |
(27,747 |
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$ |
(15,182 |
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Net loss per share, basic and diluted |
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$ |
(0.48 |
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$ |
(2.58 |
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Weighted-average number of common shares used in computing |
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58,382,444 |
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5,892,145 |
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Page 5 of NUMPAGES 6
Day One Biopharmaceuticals, Inc.
Selected Consolidated Balance Sheet Data
(unaudited)
(In thousands)
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March 31, |
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December 31, |
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Cash and cash equivalents |
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$ |
262,731 |
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$ |
284,309 |
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Total assets |
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267,779 |
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289,821 |
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Total liabilities |
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8,176 |
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8,673 |
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Accumulated deficit |
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(155,234 |
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(127,487 |
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Total stockholders’ equity |
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259,603 |
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281,148 |
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#####
Page 6 of NUMPAGES 6
Targeted Therapies for People of All Ages May 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, 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, our ability to obtain regulatory approval, the potential therapeutic benefits and economic value of our product candidates, potential growth opportunities, competitive position, industry environment and potential market opportunities, 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: Cancer Drug Development for People of All Ages Mission That Creates Value Specialized Team Tovorafenib (DAY101) Lead Program Growing Portfolio and Runway Beyond Clinical Milestones Develop medicines for genomically-defined cancers Goal is to establish first-in-class position through rapid pediatric registration Expand to adult populations in parallel Deep expertise in oncology, pediatric, and rare disease development, registration, and commercialization Extensive network in the global pediatric oncology community Proven track record of success in building biopharma companies Potential to be first-in-class oral, CNS-penetrant pan-RAFi Potentially the first approval in a market with no standard of care Monotherapy CRs and PRs in pediatric low-grade glioma (pLGG) Breakthrough Therapy Designation, Rare Pediatric Disease Designation Two clinical-stage MEKi assets, in-licensed for combination trial Projected cash runway into 2024 Capital through pivotal data in pLGG and early adult solid tumor Phase 1b data
Pediatric Markets Create Opportunity for High Impact and Capital Efficiency Lack of approved products create potential first-in-class opportunities Pricing flexibility for important new therapies Supportive and engaged advocacy and investigator community desiring better treatment options Early engagement with global regulatory authorities Small trials and clear endpoints that permit rapid development to clinical proof-of-concept and potential approval Many pediatric tumors are genetically simple and genomically stable Genetic alterations are often oncogenic Rapid clinical development Enriched responder populations informed by underlying biology Regulatory and reimbursement tailwinds
A Senior Team with Deep Experience Developing and Commercializing Products in Pediatric and Adult Oncology Markets Mike Preigh, PhD Chief Technical Officer Head of CMC at Array for 10+ years. Brought >20 drug candidates to IND & clinical development Lisa Bowers Chief Commercial Officer CEO of Rhia Ventures, COO of The Tara Health Foundation, VP of the North American Supply Chain and Commercial Leader at Genentech Davy Chiodin, PharmD Chief Development Officer VP Regulatory Science, Acerta/AZ; Global Regulatory Leader, Pediatric Oncology, Roche/Genentech Samuel Blackman, MD, PhD Chief Medical Officer & Founder Pediatric Heme/Onc and Neuro-Onc; Oncology Clinical Development at Mavupharma, Silverback, Juno, Seattle Genetics, GSK Jeremy Bender, PhD, MBA Chief Executive Officer VP of Corporate Development at Gilead; COO Tizona Therapeutics; CBO Sutro Biopharma; founding Board member of VaxCyte Charles York II, MBA Chief Operating and Financial Officer CFO and Head of Corporate Development at Aeglea; Consulting CFO at Bridgepoint Consulting; PricewaterhouseCoopers Jaa Roberson Chief People Officer Head of Human Resources at Bellicum Pharmaceuticals; Human Resources Roles at Achaogen, Roche/Genentech
Our Pipeline Product Candidate Indication Preclinical Phase 1 Phase 2 Phase 3 Milestones Tovorafenib (DAY101) Type II Pan-RAF Inhibitor Relapsed pLGG Frontline pLGG RAF-altered solid tumors2 (monotherapy) Pimasertib MEK 1/2 Inhibitor MAPK-altered solid tumors3 (Combo w/Tovorafenib) FDA Breakthrough Therapy Designation FDA Orphan Drug Designation EC Orphan Designation FDA Rare Pediatric Disease Designation (PRV Eligible) FIREFLY-11 (pivotal) FIREFLY-2 (planned) FIRELIGHT-1* FIRELIGHT-1* 2DAY101 adult monotherapy Phase 1 dose escalation and expansion trial previously completed 3Pimasertib Phase 1 dose escalation and expansion trial previously completed *Includes patients ≥12 years of age pLGG = pediatric low-grade glioma 1Pivotal Phase 2 trial expected to support registration Enrollment complete: May 2022 Initial data: June 2022 Topline data: 1Q 2023 Phase 3 initiation: 2Q 2022 First patient dosed: November 2021 Phase 1b/2 initiated: March 2022
Tovorafenib (DAY101) Type II Pan-RAF Inhibitor
Tovorafenib (DAY101): Monotherapy Approach is Focused on RAF Fusions While Our Combination Strategy Addresses a Broad Set of MAPK Alterations Tovorafenib (DAY101) is a type II RAF inhibitor that selectively inhibits both monomeric and dimeric RAF kinase Tovorafenib’s inhibition of both RAF monomers and dimers makes it a unique monotherapy approach for patients with tumors driven by RAF wild-type fusions, and a bespoke therapy for pediatric low-grade gliomas Unlike type I RAF inhibitors, tovorafenib does not cause paradoxical activation in RAF wild-type cells Approved BRAF products (e.g. vemurafenib, encorafenib) are type I RAF inhibitors that only inhibit RAF monomers and are therefore limited to use in BRAF V600-altered tumors Type I inhibitors can also cause paradoxical activation of the MAPK pathway, which could potentially lead to increased tumor growth Adapted from: Yaeger and Corcoran, Cancer Discovery, 2019 Type I Type II BRAF V600E ATP BRAF V600E Drug BRAF V600E Drug RAF ATP RAF ATP RAF Drug RAF ATP RAF RAF Drug Drug RAF monomeric kinase RAF dimeric kinase Momomer-selective RAF inhibitor (e.g. vemurafenib, dabrafenib, encorafenib) RAF dimer inhibitor (e.g., LXH254, LY3009120) Tovorafenib (DAY101), in combination with MEK inhibitors, may act synergistically to inhibit tumors driven by other MAPK alterations and broadens its potential clinical applications
The Current pLGG Treatment Paradigm Reflects the Unrelenting Nature of this Chronic Brain Tumor 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. Surgical Intervention Chemo (90%) Other (<5%) Targeted Tx (5-10%) Suspected pLGG GTR No Recurrence Eventual Recurrence 80% 20% 35% Presentation 1L 2L 3L Response, no recurrence ~35% Chemo (50%) Other (<5%) Targeted Tx (40-50%) Chemo (35%) Other (<20%) Targeted Tx (40-50%) Response, no recurrence ~50% ~65% ~50% Biopsy Only 40% 20% Molecular Testing Biopsy1 (>95%) No Biopsy (5%) ≤ Partial Resection ~50% Additional lines of therapy 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
PNOC014 Study Results Demonstrated Responses or Stable Disease in Majority of pLGG Patients Treated with Tovorafenib (DAY101) Of the eight patients with RAF fusions (7 BRAF, 1 CRAF), two patients achieved a complete response by Response Assessment for Neuro-Oncology (RANO), three had a partial response, and two achieved prolonged stable disease Median time to achieve a response was 10.5 weeks, with most common side effects being skin rash and hair color changes. Most patients treated up to two years at 420 mg/m2/week US FDA has granted DAY101 Breakthrough Therapy designation for the treatment of pediatric patients with advanced low-grade glioma harboring RAF alteration and Orphan Drug Designation for the treatment of malignant glioma Tovorafenib (DAY101) studied as once-weekly monotherapy in a Phase 1 dose escalation trial in relapsed pediatric glioma patients conducted by the Dana-Farber Cancer Institute and the Pacific Pediatric Neuro-Oncology Consortium (PNOC) Once Weekly Tovorafenib (DAY101) Complete Response Partial Response Prolonged Stable Disease
Results from Independent Radiology Review of PNOC014 RAPNO: Response assessment for pediatric neuro-oncology (exploratory) RANO: Response assessment for neuro-oncology (FDA standard) Volumetric image analysis (exploratory) Best response from baseline Date of data cutoff: 02 JAN 2020 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 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 Toxicities Grade 1-2 Grade 3 Grade 4 Anemia 6 (67%) Hypophosphatemia 4 (44%) Fatigue 5 (55%) Rash 8 (89%) Achromotrichia 7 (78%) Pruritis 6 (67%) Photosensitivity 1 (11%) Nevus 7 (78%) Alopecia 3 (34%) Epistaxis 2 (22%) Dry skin 3 (34%) Myalgias/arthralgias 3 (34%) Anorexia 2 (22%) Cheilitis 3 (34%) Hypermagnesemia 1 (11%) Bleeding gums 1 (11%) Increased AST 4 (44%) Nausea/vomiting 3 (33%) CPK elevation 1 (11%) Weight loss 2 (22%) DAY101 AE summary Most common toxicity: skin AEs reversible and all manageable Single, reversible Grade 3 event No Grade 4 AEs No dose reductions (vs. 40% of patients on selumetinib montherapy required dose reductions) Drug-related AEs for Tovorafenib (DAY101) Toxicities Grade 1-2 Grade 3 Grade 4 Increased ALT 20 (40%) 1 (2%) CPK elevation 34 (68%) 5 (10%) Diarrhea 27 (54%) 2 (4%) Decreased ejection fraction 19 (38%) 1 (2%) Gastric haemorrhage 1 (2%) Headache 14 (28%) 1 (2%) Decreased lymphocyte count 19 (38%) 1 (2%) Neutropenia 14 (28%) 3 (6%) Paronychia 19 (38%) 3 (6%) Rash (acneiform) 29 (58%) 2 (4%) Rash (maculopapular) 26 (52%) 5 (10%) Skin infection 7 (14%) 1 (2%) Tooth infection 1 (2%) Weight gain 5 (10%) 1 (2%) Vomiting 22 (44%) Nausea 21 (42%) Increased AST 25 (50%) Anemia 28 (56%) Pruritis 10 (20%) Dyspnea 30 (60%) Drug-related AEs for selumetinib Date of DAY101 data cutoff: 02 JAN 2020; Wright K et. al. Neuro Oncology Abstract CTNI-19. 2020; Fangusaro J et al. Lancet Oncol 2019
Pivotal Phase 2 Study of Monotherapy Tovorafenib (DAY101) in pLGG (FIREFLY-1) Abbreviations: LGG, low-grade glioma; ORR, objective response rate; C, cycle; D, day Study Design Screening Day –28 to 0 Enrollment/Baseline (C1D1) MRI: Baseline and every 3rd cycle Study Drug Administration 420mg/m2 QW Eligibility evaluation Treatment period: minimum of 2 years or until progression or toxicity/intolerability C27D1 After Cycle 27: patients may either continue treatment or enter drug holiday period at any time (at discretion of Investigator) End of Study (Patient #60, Cycle 27) Trial Design Single arm, open-label, global registrational phase 2 study n = 60 patients (approximately) Eligibility: Patients aged 6 months – 25 years with LGG harboring a KIAA1549:BRAF wild-type fusion or BRAF V600 mutation Endpoints Primary endpoint: ORR based on RANO criteria, assessed by independent review Secondary endpoints: ORR by RAPNO criteria; EFS; safety
Key Product Attributes for pLGG Prescribers When Choosing a New Therapy Relative Importance of attributes PFS & ORR Safety while on therapy Functional Improvement & Long-Term Safety Dosing and Administration FDA Approval “You want to make sure the treatment is not worse than the disease, and you are not making their QoL worse. These are just children.” “As we are dealing with the brain, we need to make sure these patients can function. We want to make sure they can do their daily activity, and maintain motor functions and vision… this is very important for their QoL.” “Pediatric dosing is very important, but efficacy and safety are a lot more important than the delivery of the drug.” “Efficacy, especially ORR and PFS, are the most important. You want these patients to live without progression of pLGG for as much time as possible, and for the treatment to be effective for the majority of these patients.” MOA “Without an indication, insurance may not pay for it… it would be a higher burden for families… an FDA-approved indication also means the therapy meets general safety and efficacy regulations, so that is always a plus.” “I don’t really care about the mechanism of action, as long as the drug works, and there are no big concerns with toxicity.” Stable Disease “We tell our patients that the goal is to kill the tumor, but the more practical goal is to stop it from growing. Even if we achieve stable tumors, that’s considered a success.” Sources: pLGG Buying Process; pLGG Demand Study
Incidence and Prevalence of BRAF-altered pLGG in the U.S. 2020 Estimated Incidence Under 25 US Population1 ~105,000,000 Rate of CNS Tumors (0.00521%)2 ~5,500 Gliomas (63%)2 ~3,500 Low Grade (77%)2 ~2,600 Has Received Drug Tx (58%)2 ~1,500 BRAF Mutated (70%)2 ~1,100 2017 Estimated SEER Prevalence Under 25 NA ~130,0003 ~82,000 ~63,000 ~36,000 ~26,000 ~1,100 Estimated Annual Incidence ~26,000 Estimated Prevalence (SEER) 1US Census; 2CBTRUS, Qaddoumi et al 2009, Schreck et al 2019, ClearView Analysis; 3SEER US complete prevalence counts of patients aged under 25 with Brain and Other Nervous Systems tumors as of January 1, 2017. Estimated annual incidence and estimated prevalence (SEER) are Day One calculations based on publicly available data.
Our Pipeline Product Candidate Indication Preclinical Phase 1 Phase 2 Phase 3 Anticipated Milestones Tovorafenib (DAY101) Type II Pan-RAF Inhibitor Relapsed pLGG Frontline pLGG RAF-altered solid tumors2 (monotherapy) Pimasertib MEK 1/2 Inhibitor MAPK-altered solid tumors3 (Combo w/Tovorafenib) FDA Breakthrough Therapy Designation FDA Orphan Drug Designation EC Orphan Designation FDA Rare Pediatric Disease Designation (PRV Eligible) FIREFLY-11 (pivotal) FIREFLY-2 (planned) FIRELIGHT-1* FIRELIGHT-1* 2DAY101 adult monotherapy Phase 1 dose escalation and expansion trial previously completed 3Pimasertib Phase 1 dose escalation and expansion trial previously completed *Includes patients ≥12 years of age pLGG = pediatric low-grade glioma 1Pivotal Phase 2 trial expected to support registration Phase 3 initiation: 2Q 2022 First patient dosed: November 2021 Phase 1b/2 initiated: March 2022 Enrollment complete: May 2022 Initial data: June 2022 Topline data: 1Q 2023
Tovorafenib (DAY101) is Active as a Monotherapy in Patients with RAF-altered Adult Solid Tumors and Has Shown Strong Synergy Preclinically in Combination Clinical activity demonstrated in relapsed melanoma patients; preclinical activity demonstrated in RAF fusions, BRAF non-V600 mutations, and BRAF V600 mutations Less frequent and less severe acneiform rash No observed ophthalmologic liabilities (RVO/CSR) No observed CV liabilities (changes in LVEF) No type I BRAF SAEs: SCCs/KAs, pyrexia, arthralgia Same study will include combination cohorts of tovorafenib (DAY101) + pimasertib First patient dosed in Phase 2 monotherapy study in November 2021 >225 adult patient exposures Responses in BRAF V600E mutant tumors similar to type I BRAF inhibitors Responses in relapsed BRAF and NRAS-mutant melanoma, suggesting tovorafenib (DAY101) may be active in tumors currently unaddressed by approved Type I BRAF inhibitors Differentiated safety profile for tovorafenib (DAY101) vs. existing BRAF and MEK inhibitors We initiated an adult solid tumor study to further evaluate monotherapy tovorafenib (DAY101) in patients with RAF altered 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
Activity of Tovorafenib (DAY101) in SNX8:BRAF Fusion Spindle Cell Sarcoma Baseline After 2 cycles of tovorafenib Diagnosis BRAF fusion (FISH) CR PD CR Subtotal resection Gemcitabine, docetaxel Trametinib Ifosfamide, doxorubicin, dexrazoxane Proton radiotherapy SNX8-BRAF fusion Months -30 -24 -18 -12 -6 0 6 Tovorafenib Tovorafenib After the first dose of 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 A male child with spindle cell sarcoma, 5-years of age at diagnosis
Next-generation RAF Inhibitors are Unique in Their Ability to Address Adult Cancers Associated with RAF Wild-type Fusions Botton T et al, Cell Reports, 2019 LY3009120: Lilly pan-RAFi Lifirafenib: Beigene pan-RAF/EGFRi CCT196969: CRUK RAF ”paradox breaker” Springworks 2020 Corp Presentation BRAFwt fusion mixed Mullerian cancer BRAFwt fusion, melanoma Day One/CrownBio internal data E5251-U2001 (Sep 2020) Only tovorafenib (DAY101) has demonstrated monotherapy clinical activity in KIAA1549:BRAF and SRGAP3:CRAF wild-type fusions in pLGG Gouda M et al, ESMO 2020 CR observed at 1800 mg BID = 3x higher total AUC over 900 mg BID Activity of BRAF dimer-breaker PLX-8394 in BRAF wild-type fusion melanoma
Phase 2 Study of Monotherapy Tovorafenib (DAY101) in Solid Tumors (FIRELIGHT-1) Trial Design1 Single arm, open-label, global phase 1b/2a study n = 40 patients (approximately) Eligibility: Patients aged 12 years and older with non-hematologic tumor with an activating BRAF fusion, CRAF/RAF1 fusion, or CRAF/RAF1 amplification Endpoints Primary endpoint: ORR by RECIST version 1.1 for non-CNS solid tumors and RANO criteria for any CNS tumors Secondary endpoints: safety and additional efficacy parameters DAY101 QW until disease progression2 Safety Follow Up Patients with a known BRAF or CRAF/RAF1 fusion, or CRAF/RAF1 amplification Melanoma cohort “Tissue agnostic” cohort Study Drug Administration ≥ 18 years at 600 mg PO QW 12 to <18 years at 420mg/m2 PO QW Abbreviations: ORR, objective response rate; QW, once weekly ; PO, by mouth; BRAF, B-Raf proto-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). 2DAY101 QW until disease progression, intolerable toxicity, withdrawal of consent, or death
Strong Scientific Rationale for Combining Tovorafenib (DAY101) with Additional MAPK Pathway Inhibitors Potential combinations Type II RAFi + MEKi Rationale BRAF fusion dimers are effectively inhibited by type II, but not type I RAFi MEK ERK RAF/MEK/ ERK PI3K/mTOR RAL Type II RAFi + Targeting multiple nodes of MAPK pathway will drive deeper and more durable response Signaling pathways Proliferation, survival Proliferation, survival RAS/RAF/MEK/ERK PI3K/ mTOR Proliferation, survival Type II RAFi + SHP2i Targeting multiple pathways will drive deeper response Type II RAFi + Non V600 BRAF dimers are effectively inhibited by type II, but not type I, RAFi MEK ERK Proliferation, survival SHP2i MEKi or SHP2i MEKi or KRAS- G12Ci or BRAF non-V600 BRAF or CRAF WT fusion KRAS or NRAS mutant NF1 LOF
Pimasertib MEK1/2 Inhibitor
Pimasertib: Allosteric MEK1/2 Inhibitor with Demonstrated Activity in MAPK-driven 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. Pimasertib is an 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 Source: Hepner, Salgues, Anjos, et al. 2017. GF RTKS NRAS BRAF MEK ERK Cell growth and survival Nuclear membrane GTP Gene transcription Cellular membrane MEKi BRAFi
Vertical MAPK Pathway Inhibition with Tovorafenib (DAY101) and Pimasertib Unlocks Potential Synergy for Adult Solid Tumors 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 Combination therapy with a MEK inhibitor and type II RAF inhibitor is synergistic in KRASmut and BRAFmut tumor models Mechanistic model for vertical MAPK pathway inhibition (modified from Yen et al. Cancer Cell, 2018) . DAY101 + MEK inhibitor is synergistic in KRAS G12C and Q61 mutant tumor cell models (Day One internal data) Sensitivity of KRAS Q61 mutant cells to pimasertib is enhanced when cells are treated with the type II RAF inhibitor BGB-283 (Yuan et al., Mol Onc 2020) Modified from Yen et al. Cancer Cell, 2018 A B C
Tovorafenib (DAY101) / Pimasertib Combination to be Evaluated in Solid Tumors (FIRELIGHT-1) 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 Trial Design1 Combination dose escalation, global phase 1b/2 study2 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 Endpoints Phase 1b: PK, PD and Safety, MTD/RP2D Phase 2: Efficacy (ORR, DOR) DAY101 + Pimasertib until disease progression3 NRASmut Selected tumors BRAF Class 1 (non-E/K) and Class 2 mutant tumors BRAF wt fusion selected tumors Pre-identified patients with advanced solid tumors and available clinical molecular profiling information. *Additional biomarker-selected cohorts may be pursued based on developing data Safety Follow Up Tumors with MAPK pathway alterations Phase 1b Phase 2*
Summary
Financial Summary: DAWN Cash and cash equivalents as of March 31, 2022: $262.7 million (no debt) 61.9 million shares of common stock outstanding $ Millions Three Months Ended 3/31/22 Three Months Ended 3/31/21 R&D Expense $15.0 $12.6 G&A Expense $12.7 $3.5 Net Loss $27.7 $16.1 All financial and share information is unaudited Projected cash runway into 2024 FIREFLY-1: Pivotal Phase 2 clinical trial of tovorafenib (DAY101) Enrollment complete in May 2022 Initial clinical data expected in June 2022 Full topline results expected in 1Q 2023 Anticipated NDA filing in 2023, if data from FIREFLY-1 are supportive FIRELIGHT-1: Tovorafenib (DAY101) and pimasertib combination Trial initiated in March 2022
Momentum for a More Inclusive Era of Drug Development, Starting at Day One Pursuing Fast-to-Market Pediatric and Adult Targeted Therapies Key Highlights Tovorafenib (DAY101)1 FIREFLY-1 (Relapsed pLGG) First patient dosed in Pivotal FIREFLY-1 trial: May 2021 Enrollment complete in May 2022 Breakthrough Therapy Designation & Rare Pediatric Disease Designation FIRELIGHT-1 (RAF-altered solid tumors - monotherapy) First patient dosed in phase 2 monotherapy trial: November 2021 Intellectual Property Composition of matter to mid-2030s with PTE, potential exclusivity to late 2030s / early 2040s via broad patent portfolio Pimasertib1 FIRELIGHT-1 (MAPK-altered solid tumors – Combo w/Tovorafenib) Initiated combination dose escalation, global phase 1b/2 trial: March 2022 2022 Outlook Tovorafenib (DAY101) FIREFLY-1 (Relapsed pLGG) Initial data expected: June 2022 Topline data expected: 1Q 2023 FIREFLY-2 (Frontline pLGG) Phase 3 trail initiation: 2Q 2022 1 Worldwide rights for all indications
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