UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): August 10, 2021
DAY ONE BIOPHARMACEUTICALS, INC.
(Exact name of registrant as specified in its charter)
| Delaware | 001-40431 | 83-2415215 | ||
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
| 395 Oyster Point Blvd., Suite 217 South San Francisco, CA |
94080 | |
| (Address of principal executive offices) | (Zip Code) |
(650) 484-0899
(Registrant’s telephone number, including area code)
N/A
(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:
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading symbol(s) |
Name of each exchange on which registered | ||
| Common Stock, $0.0001 Par Value Per Share | DAWN | The Nasdaq Stock Market LLC (Nasdaq Global Select Market) |
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 August 10, 2021, Day One Biopharmaceuticals, Inc. issued a press release announcing its financial results for the quarter ended June 30, 2021. A copy of the press release is attached as Exhibit 99.1 to this report.
The information in this Item 2.02, including Exhibit 99.1 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 Item 2.02 and in the accompanying Exhibit 99.1 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 7.01 Regulation FD Disclosure.
On August 10, 2021, the Company also updated its corporate presentation. A copy of the corporate presentation is attached as Exhibit 99.2 to this report.
The information in this Item 7.01, including Exhibit 99.2 to this report, shall not be deemed to be “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act. The information contained in this Item 7.01 and in the accompanying 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 |
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| DAY ONE BIOPHARMACEUTICALS, INC.
| ||||||
| Date: August 10, 2021 | By: | /s/ Charles N. York II, M.B.A. | ||||
| Chief Operating Officer and Chief Financial Officer | ||||||
Exhibit 99.1
Day One Reports Second Quarter 2021 Financial Results and Corporate Progress
DAY101 Granted Rare Pediatric Disease Designation from FDA
DAY101 Granted Orphan Designation from European Commission
Dosed the First Patients in Pivotal FIREFLY-1 Clinical Trial of DAY101 in Patients with pLGG
Successfully Completed $184 Million Upsized Initial Public Offering Providing Funding into the Second Half of 2023
SOUTH SAN FRANCISCO, CA, August 10, 2021 – Day One Biopharmaceuticals (Nasdaq: DAWN), a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for patients of all ages with genomically defined cancers, today announced financial results for the second quarter of 2021 and highlighted recent corporate achievements.
“Day One made significant progress across multiple clinical and corporate initiatives during the second quarter of 2021, including dosing the first patients in our ongoing FIREFLY-1 pivotal study of DAY101 in pediatric low-grade glioma,” said Jeremy Bender, Ph.D., chief executive officer of Day One. “The success of our recent IPO reflects a strong commitment from our investors who, like all of us at Day One, recognize the therapeutic potential of DAY101. Entering the second half of 2021, we remain well positioned to advance our pipeline through key data readouts with the goal of fulfilling our mission of developing novel medicines to improve the lives of patients of all ages living with cancer.”
Program Highlights
| • | The Company announced first patients dosed in the FIREFLY-1 pivotal clinical trial of DAY101 in pediatric low-grade glioma (pLGG). FIREFLY-1 is being conducted in collaboration with the Pacific Pediatric Neuro-Oncology Consortium (PNOC) and is designed to support the regulatory approval of DAY101. Initial data from FIREFLY-1 is expected in the first half of 2022. |
| • | Day One has initiated a Phase 2 monotherapy trial of DAY101 in adult patients with recurrent, progressive, or refractory solid tumors harboring MAPK pathway aberrations. |
| • | The U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation to DAY101 for the treatment of low-grade gliomas harboring an activating RAF alteration that disproportionately affects children. If a New Drug Application in the United States for DAY101 is approved, Day One may be eligible to receive a Priority Review Voucher (PRV) from the FDA, which can be redeemed to obtain priority review for any subsequent marketing application or may be sold or transferred. |
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| • | The European Commission granted DAY101 Orphan Designation for the treatment of glioma based upon a positive opinion from the European Medicines Agency Committee for Orphan Medicinal Products. |
Corporate Highlights
| • | The Company announced the successful closing of its upsized initial public offering, raising gross proceeds of $184.0 million, bringing total cash, cash equivalents and marketable securities to $310.0 million at the end of June 30, 2021. The company expects its current cash position to fund operations into the second half of 2023 and through key clinical milestones. |
| • | Day One appointed Saira Ramasastry to its Board of Directors. Ms. Ramasastry currently serves as the Managing Partner of Life Sciences Advisory, LLC, and brings more than 20 years of experience to the Board as a life sciences-focused strategic consultant and investment banker. |
Second Quarter 2021 Financial Highlights
| • | Cash Position: Cash and cash equivalents and short-term investments totaled $310.0 million at June 30, 2021. Based on Day One’s current operating plan, management believes it has sufficient capital resources to fund anticipated operations into the second half of 2023. |
| • | R&D Expenses: Research and development expenses were $9.9 million for the second quarter 2021 and $1.4 million for the second quarter 2020. The increase was primarily due to additional employee compensation costs, clinical trial expenses, CMC activity and a milestone payment for DAY101. |
| • | G&A Expenses: General and administrative expenses were $5.5 million for the second quarter 2021 and $0.9 million for the second quarter 2020. The increase was primarily due to additional employee compensation costs, legal, and professional expenses associated with being a public company. |
| • | Net Loss: Net loss totaled $15.5 million and $2.4 million for the second quarter 2021 and 2020, respectively, with non-cash stock compensation expense of $2.5 million and $0.1 million for the second quarter of 2021 and 2020, respectively. |
Upcoming Events
| • | 12th Annual Wedbush PacGrow Healthcare Conference: Day One’s chief executive officer Jeremy Bender will be a participant on the Panel, “Bullseye – Targeted Oncology Part 2”. The panel discussion will take place on Wednesday, August 11th at 10:20 am ET. Day One will also be available for one-on-one investor meetings during the conference. |
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About DAY101
DAY101 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. Studies have shown DAY101 has high brain distribution and exposure in comparison to other MAPK pathway inhibitors, thus potentially benefiting patients with primary brain tumors or brain metastases of solid tumors. DAY101 is a type II RAF inhibitor found to selectively inhibit both monomeric and dimeric RAF kinase, which may broaden its potential clinical application to treat an array of RAF-altered tumors.
DAY101 has been studied in over 250 patients, and as a monotherapy demonstrated good tolerability and encouraging anti-tumor activity in pediatric and adult populations with specific MAPK pathway-alterations. In November 2020, Day One announced preliminary results from PNOC014, an ongoing Phase 1 Pacific Pediatric Neuro-Oncology Consortium (PNOC) network study with DAY101 sponsored by the Dana-Farber Cancer Institute. Preliminary results demonstrated that of the eight relapsed pLGG patients in the study with RAF fusions, two patients achieved a complete response by Response Assessment for Neuro-Oncology (RANO), three had a partial response, two achieved prolonged stable disease, and one experienced progressive disease. DAY101 also demonstrated a tolerable safety profile with the most common side effects being skin rash and hair color changes.
DAY101 has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pLGG harboring an activating RAF alteration who require systemic therapy and who have either progressed following prior treatment or who have no satisfactory alternative treatment options. The FDA has also granted Rare Pediatric Disease Designation to DAY101 for the treatment of low-grade gliomas harboring an activating RAF alteration that disproportionately affects children. In addition, DAY101 has received Orphan Drug designation from the FDA for the treatment of malignant glioma and orphan designation from the European Commission for the treatment of glioma.
Day One is conducting a pivotal Phase 2 trial (FIREFLY-1) of DAY101 in pediatric, adolescent and young adult patients with pLGG. Day One also plans to study DAY101 alone or in combination with other agents that target key signaling nodes in the MAPK pathway, such as the Company’s MEK inhibitor pimasertib, in patient populations where various RAS and RAF alterations are believed to play an important role in driving disease.
About Day One Biopharmaceuticals
Day One Biopharmaceuticals is a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for patients of all ages with genomically defined cancers. Day One was founded to address a critical unmet need: children with cancer are being left behind in a cancer drug development revolution. Our name was inspired by the “The Day One Talk”1 that physicians have with patients and their families about an initial cancer diagnosis and treatment plan. We aim to re-envision cancer drug development and redefine what’s possible for all people living with cancer—regardless of age—starting from Day One.
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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, DAY101, is an oral, highly-selective type II pan-RAF kinase inhibitor, and is being evaluated in a pivotal Phase 2 clinical trial (FIREFLY-1) in pediatric, adolescent and young adult patients with recurrent or progressive low-grade glioma (pLGG). The Company’s pipeline also includes the investigational agent pimasertib, a clinical-stage, oral, small molecule found to selectively inhibit mitogen-activated protein kinase kinases 1 and 2 (MEK). Through Day One and its collaborators, cancer drug development comes of age. Day One is based in South San Francisco. For more information, please visit www.dayonebio.com.
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.
1 Jennifer W. Mack and Holcombe E. Grier; Journal of Clinical Oncology 2004 22:3, 563-566
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Day One Biopharmaceuticals, Inc.
Consolidated Statements of Operations and Comprehensive Loss
(unaudited)
(In thousands)
| Three Months Ended June 30, |
||||||||
| 2021 | 2020 | |||||||
| Operating expenses: |
||||||||
| Research and development |
$ | 9,914 | $ | 1,437 | ||||
| General and administrative |
5,525 | 872 | ||||||
|
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|||||
| Total operating expenses |
15,439 | 2,309 | ||||||
|
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|
|
|
|||||
| Loss from operations |
(15,439 | ) | (2,309 | ) | ||||
|
|
|
|
|
|||||
| Interest expense |
(7 | ) | (10 | ) | ||||
| Other expense |
(27 | ) | — | |||||
| Changes in fair value of derivative tranches liability |
— | (90 | ) | |||||
|
|
|
|
|
|||||
| Net loss and comprehensive loss |
(15,473 | ) | (2,409 | ) | ||||
| Net loss attributable to redeemable convertible noncontrolling interests |
(1,191 | ) | (649 | ) | ||||
| Exchange of redeemable noncontrolling interest shares – deemed dividend* |
(99,994 | ) | — | |||||
|
|
|
|
|
|||||
| Net loss attributable to common share members / common stockholders |
$ | (114,276 | ) | $ | (1,760 | ) | ||
|
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| Net loss per share, basic and diluted |
$ | (5.04 | ) | $ | (0.32 | ) | ||
|
|
|
|
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| Weighted-average number of common shares used in computing net loss per share, basic and diluted |
22,661,889 | 5,456,203 | ||||||
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| * | The exchange of redeemable non-controlling interest shares for Company common stock was accounted for as a non-cash, deemed dividend. See Note 13 in the form 10-Q filed on August 10, 2021 for further information. |
Day One Biopharmaceuticals, Inc.
Selected Consolidated Balance Sheet Data
(unaudited)
(In thousands)
| June 30, 2021 |
December 31, 2020 |
|||||||
| Cash and cash equivalents |
$ | 309,996 | $ | 43,728 | ||||
| Total assets |
316,537 | 45,661 | ||||||
| Total liabilities |
4,774 | 2,200 | ||||||
| Accumulated deficit |
(86,308 | ) | (56,842 | ) | ||||
| Total stockholders’ equity /members’ (deficit) |
311,763 | (54,205 | ) | |||||
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Contacts:
Media:
1AB
Dan Budwick
dan@1abmedia.com
Investors:
LifeSci Advisors
Hans Vitzthum
hans@lifesciadvisors.com
#####
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Cancer Drug Development for Patients of All Ages AUGUST 2021 Exhibit 99.2
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 development activities, 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 in under the heading “Risk Factors” contained in the final prospectus on Form 424B filed with the Securities and Exchange Commission (“SEC”) on May 26, 2021, 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. By attending or receiving this presentation you acknowledge that you will be solely responsible for your own assessment of the market and our market position and that you will conduct your own analysis and be solely responsible for forming your own view of the potential future performance of our business. 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. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction.
Day One: Cancer Drug Development for Patients of All Ages A Mission that Creates Value 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 Specialized Team Rare Pediatric Disease Designation, Breakthrough Therapy Designation, pivotal Phase 2 study with first patient dosed in May 2021, and expected NDA filing in 2023, if the data from FIREFLY-1 are supportive Potentially the first approval in a market with no standard of care Development plan based on clinical POC demonstrated in pediatric and adult cancers with known oncogenic tumor alterations, with a safety database of >250 patients >50% monotherapy ORR in pediatric low-grade glioma (pLGG) Potential to be a first-in-class oral, CNS-penetrant pan-RAFi DAY101 Lead Program Develop medicines for genomically-defined cancers Goal is to establish first-in-class position through rapid pediatric registration Expand to adult populations in parallel 1Q21 in-license of two clinical-stage MEKi assets $350M+ in capital raised to date funds through pivotal data in pLGG and early adult solid tumor Phase 1b data Access Biotechnology, Atlas Ventures, Boxer Capital, BVF Partners, Canaan, Franklin Templeton, Janus Henderson Investors, Perceptive Advisors, RA Capital Management, T. Rowe Price Associates, and Viking Global Investors Growing Portfolio and Strong Investor Base
Pediatric Markets Create Opportunity for High Impact and Capital Efficiency Few approved products create potential first-in-class opportunities Pricing flexibility for important new therapies Supportive and engaged advocacy and investigator community waiting for better treatment options Early engagement with global regulatory authorities Small trials and clear endpoints that permit rapid development to proof-of-concept and potential approval Many pediatric tumors are genetically simple and genomically stable Genetic alterations are often oncogenic Rapid clinical development like other rare diseases Enriched responder populations informed by underlying biology Regulatory and reimbursement tailwinds
Significant Clinical and Business Momentum Over Last 12 Months SINGLE AGENT ACTIVITY FOR DAY 101 SENIOR LEADERSHIP APPOINTMENTS BUSINESS DEVELOPMENT/LICENSING OF MEK INHIBITORS CLINICAL PROGRAM EXPANSION RECENT ACCOMPLISHMENTS AND MILESTONES ACHIEVED Expansion of Executive Leadership Team and Board of Directors, including Jeremy Bender, Lisa Bowers, and John Josey Announced prior $60M Series A and lead clinical-stage program from Takeda Charles York Appointed COO and CFO, and Expands Board of Directors with the Addition of Natalie Holles $130 Million Series B Financing to Accelerate New Targeted Cancer Treatments for Children Q2 2020 Q3/Q4 2020 April / May 2021 Feb 2021 Appoints Saira Ramasastry to Board of Directors Announced plans to rapidly develop new cancer treatments for people of all ages Announces Preliminary Phase 1 Results for DAY101 pLGG, Breakthrough Therapy Designation (BTD) and New Phase 2 Study Expands Clinical-Stage Oncology Pipeline; Global License Agreement with Merck KGaA, Darmstadt, Germany to Develop and Commercialize MEKi Pimasertib First Patient Dosed in FIREFLY-1 Pivotal Phase 2 Clinical Trial of DAY101 in Pediatric Progressive Low-Grade Glioma Business Clinical Rare Pediatric Disease Designation from FDA and Orphan Designation from EC Initiated Adult Solid Tumor Clinical Trial Successfully completes $184M IPO June / July 2021 August 2021
A Senior Team with Deep Experience Developing and Commercializing Products in Pediatric and Adult Oncology Markets Samuel Blackman, MD, PhD Chief Medical Officer & Founder Pediatric Heme/Onc and Neuro-Onc; Oncology Clinical Development at Mavupharma, Silverback, Juno, Seattle Genetics, GSK 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 Jeremy Bender, PhD, MBA Chief Executive Officer VP of Corporate Development at Gilead; COO Tizona Therapeutics; CBO Sutro Biopharma; founding Board member of VaxCyte Davy Chiodin, PharmD Chief Development Officer VP Regulatory Science, Acerta/AZ; Global Regulatory Leader, Pediatric Oncology, Roche/Genentech Mike Preigh, PhD Chief Technical Officer Head of CMC at Array for 10+ years. Brought >20 drug candidates to IND & clinical development Charles York II, MBA Chief Operating and Financial Officer CFO and Head of Corporate Development at Aeglea; Consulting CFO at Bridgepoint Consulting; PricewaterhouseCoopers
Product Candidate Preclinical Phase 1 Phase 2 Phase 3 Anticipated Milestones DAY101 Type II Pan-RAF Inhibitor Pimasertib MEK1/2 Inhibitor *Includes patients ≥12 years of age FDA Breakthrough Therapy Designation FDA Orphan Drug Designation Our Pipeline INITIATED: Relapsed pLGG (FIREFLY-1)1 PLANNED: Frontline pLGG INITIATED: Adult RAF-altered solid tumors2,* (monotherapy) PLANNED: Adult MAPK-altered solid tumors3,* (combo w/ DAY101) 1Pivotal Phase 2 trial expected to support registration 2DAY101 adult monotherapy Phase 1 dose escalation and expansion trial previously completed 3Pimasertib Phase 1 dose escalation and expansion trial previously completed First patient dosed: 2Q2021 Initial data: 1H2022 Phase 3 initiation: 1H2022 Phase 2 initiated: August 2021 Phase 1b/2 initiation: 1Q2022 EC Orphan Designation FDA Rare Pediatric Disease Designation
DAY101: Monotherapy Approach is Focused on RAF Fusions While Our Combination Strategy Addresses a Broad Set of MAPK Alterations DAY101 is a type II RAF inhibitor that selectively inhibits both monomeric and dimeric RAF kinase DAY101’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, DAY101 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) 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 CONFIDENTIAL 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 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
PNOC014 Study Results Demonstrated Responses or Stable Disease in Majority of pLGG Patients Treated with 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 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 DAY101 Complete Response Partial Response Prolonged Stable Disease
Results from Independent Radiology Review of PNOC014 % change from baseline RAPNO: Response assessment for pediatric neuro-oncology (exploratory) RANO: Response assessment for neuro-oncology (FDA standard) Volumetric image analysis (exploratory) Wright K et. al. Neuro Oncology Abstract CTNI-19. 2020 Date of data cutoff: 02 JAN 2020 Best response from baseline
Multiple Rapid, Deep and Durable Responses Observed following Initiation of 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 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 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 Wright K et. al. Neuro Oncology Abstract CTNI-19. 2020 Fangusaro J et al. Lancet Oncol 2019 Date of DAY101 data cutoff: 02 JAN 2020
Pivotal Phase 2 Study of Monotherapy DAY101 in pLGG (FIREFLY-1) Abbreviations: LGG, low-grade glioma; ORR, objective response rate; IRC, independent review committee; C, cycle; D, day, DLT, dose-limiting toxicity, EOS, end of study, MRI, magnetic resonance imaging; SOA, schedule of assessments; SOC, System Organ Class; RP2D, recommended Phase 2 dose. 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, assesed by independent review Secondary endpoints: ORR by RAPNO criteria; EFS; safety
Incidence and Prevalence of BRAF-altered pLGG in the U.S. US Census CBTRUS, Qaddoumi et al 2009, Schreck et al 2019, ClearView Analysis SEER US complete prevalence counts of patients aged under 25 with Brain and Other Nervous Systems tumors as of January 1, 2017 Selumetinib pLGG trial (Fangusaro et al 2019), Vinblastine pLGG trial (Bouffet et al 2012), BRAF Pediatric Gliomas trial (Nobre et al 2020), 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) Estimated annual incidence and estimated prevalence (SEER) are Day One calculations based on publicly available data.
Product Candidate Preclinical Phase 1 Phase 2 Phase 3 Anticipated Milestones DAY101 Type II Pan-RAF Inhibitor Pimasertib MEK1/2 Inhibitor *Includes patients ≥12 years of age FDA Breakthrough Therapy Designation FDA Orphan Drug Designation Our Pipeline INITIATED: Relapsed pLGG (FIREFLY-1)1 PLANNED: Frontline pLGG INITIATED: Adult RAF-altered solid tumors2,* (monotherapy) PLANNED: Adult MAPK-altered solid tumors3,* (combo w/ DAY101) 1Pivotal Phase 2 trial expected to support registration 2DAY101 adult monotherapy Phase 1 dose escalation and expansion trial previously completed 3Pimasertib Phase 1 dose escalation and expansion trial previously completed First patient dosed: 2Q2021 Initial data: 1H2022 Phase 3 initiation: 1H2022 Phase 2 initiated: August 2021 Phase 1b/2 initiation: 1Q2022 EC Orphan Designation FDA Rare Pediatric Disease Designation
Clinical activity demonstrated in relapsed melanoma patients; preclinical activity demonstrated in RAF fusions, BRAF non-V600 mutations, and BRAF V600 mutations Source: Olszanski AJ et. al. European Society for Medical Oncology Congress; Poster #410P, 2017 Unpublished clinical study results 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 DAY101 + pimasertib >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 DAY101 may be active in tumors currently unaddressed by approved Type I BRAF inhibitors Differentiated safety profile for DAY101 vs. existing BRAF and MEK inhibitors We expect to initiate an adult solid tumor study mid-2021 to further evaluate monotherapy DAY101 in patients with RAF altered tumors for which there are no currently approved therapies DAY101 is Active as a Monotherapy in Patients with RAF-altered Adult Solid Tumors and Has Shown Strong Synergy Preclinically in Combination
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 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 Next-generation RAF Inhibitors are Unique in Their Ability to Address Adult Cancers Associated with RAF Wild-type Fusions Activity of BRAF dimer-breaker PLX-8394 in BRAF wild-type fusion melanoma
Strong Scientific Rationale for Combining 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: 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. 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 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 trametinib or selumetinib Pimasertib showed monotherapy clinical activity, including an improvement in median PFS versus dacarbazine in NRAS mutant melanoma Combination with DAY101 and other targeted therapies may unlock the full value of pimasertib in advanced solid tumors
Vertical MAPK Pathway Inhibition with 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. Modified from Yen et al. Cancer Cell, 2018 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) A B C
DAY101+ Pimasertib Combo Dose Escalation Pimasertib Combined with DAY101 May Have a Rapid Path to Market Biomarker-positive patients Substudy 1: DAY101 Substudy 2: DAY101+ Pimasertib Screening Enrollment Treat until progression, toxicity or withdrawal of consent Safety Follow-up BRAFwt fusion melanoma BRAFwt fusion non-melanoma solid tumors Ph1b portion waived (monotherapy dose established) NRASmut selected tumors BRAF Class 1 (non-E/K) and Class 2 mutant tumors BRAFwt fusion selected tumors Design: P1b: BOIN (adaptive) P2: Simon 2-stage (stage 1, n=10/cohort; stage 2, n=25/cohort) Key endpoints: P1b: Safety, MTD/RP2D P2: Efficacy (ORR, DOR) Combination 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 Intent to open at US and ex-US clinical trial sites Additional biomarker-selected cohorts may be pursued based on developing data Pre-identified patients with advanced solid tumors and available clinical molecular profiling information. Phase 1b Phase 2 MASTER PROTOCOL
$ Millions Three Months Ended 6/30/21 Three Months Ended 6/30/20 R&D Expense $9.9 $1.4 G&A Expense $5.5 $0.9 Net Loss $15.4 $2.3 Cash and cash equivalents as of June 30, 2021: $310.0 million (no debt) IPO on May 26, 2021: $184 million in gross proceeds, includes full exercise of underwriter’s option 61.9 million shares of common stock outstanding Financial Summary: DAWN All financial and share information is unaudited Projected cash runway into the second half of 2023 Initial clinical data for DAY 101 in pivotal FIREFLY-1 expected in first half 2022 Anticipated NDA filing for DAY 101 in pLGG in 2023, if data from FIREFLY-1 are supportive DAY101 and pimasertib combination trial expected to initiate in first quarter 2022
Re-envisioning and Redefining Drug Development for People of All Ages – Starting at Day One DAY101 Oral, CNS-penetrant, pan-RAF PIMASERTIB Oral, allosteric MEK inhibitor SPECIALIZED TEAM pLGG: most common brain tumor in children, with no approved therapies Rapid and durable responses demonstrated in heavily pre-treated pLGG patients Well-tolerated as monotherapy; no Grade 4 AEs Worldwide rights to all indications IP: composition of matter to mid-2030s with PTE, potential exclusivity to late 2030s / early 2040s via broad patent portfolio Combination with DAY101 in MAPK-altered solid tumors Clinical experience in over 800 patients Clear rationale for combo for pan-RAFi and MEKi Worldwide rights to all indications Deep experience in the space and corporate development Strategy to aggressively pursue other assets and indications Plan to Initiate Combination Trial with DAY101 1Q 2022 First Patient Dosed in Pivotal FIREFLY-1 May 2021, Initial Data 1H 2022 Initiated Adult Solid Tumor Trial August 2021 Pursuing Fast-to-Market Pediatric and Adult Targeted Therapy Opportunities
