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:
Securities registered pursuant to Section 12(b) of the Act:
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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 October 30, 2024, Day One Biopharmaceuticals, Inc. (the "Company") issued a press release announcing its financial results for the quarter ended September 30, 2024. A copy of the press release is attached as Exhibit 99.1 to this report. A copy of the Company’s presentation with respect to its financial results for the quarter ended September 30, 2024 is attached as Exhibit 99.2 to this report.
Item 7.01 Regulation FD Disclosure.
On October 30 2024, the Company updated its corporate presentation. A copy of the updated presentation is attached as Exhibit 99.3 to this report.
The information in this Current Report on Form 8-K, including Exhibit 99.1, Exhibit 99.2 and Exhibit 99.3 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, Exhibit 99.2 and Exhibit 99.3 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 |
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Exhibit Number |
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Description |
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99.1 |
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99.2 |
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99.3 |
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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: |
October 30, 2024 |
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 Third Quarter 2024 Financial Results and Corporate Progress
Achieved $20.1 million in OJEMDATM (tovorafenib) net product revenue
Ended the third quarter with $558.4 million in cash, cash equivalents and short-term investments
Company to host conference call and webcast today, October 30, 4:30 p.m. Eastern Time
BRISBANE, Calif., Oct. 30, 2024 – Day One Biopharmaceuticals, Inc. (Nasdaq: DAWN) (“Day One” or the “Company”), a biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, today announced its third quarter 2024 financial results and highlighted recent corporate achievements.
“Our third quarter results demonstrate continued patient demand for OJEMDA, driven by the need for new therapies for children living with pediatric low-grade glioma,” said Jeremy Bender, Ph.D., chief executive officer of Day One. “Looking ahead to 2025, we plan to continue to drive growth by advancing our programs and pipeline, including DAY301, a potential first-in-class ADC targeting PTK7 that we expect to be in the clinic in the coming months.”
Program Highlights
Exhibit 99.1
Corporate Highlights and Upcoming Milestones
Third Quarter 2024 Financial Highlights
Upcoming Events
Conference Call
Day One will host a conference call and webcast today, October 30 at 4:30 p.m. Eastern Time. To access the live conference call by phone, dial 877-704-4453 (domestic) or 201-389-0920 (international), and
Exhibit 99.1
provide the access code 13745150. Live audio webcast will be accessible from the Day One Investors & Media page. To ensure a timely connection to the webcast, it is recommended that participants register at least 15 minutes prior to the scheduled start time. An archived version of the webcast will be available for replay on the Events & Presentations section of the Day One Investors & Media page for 30 days following the event.
About OJEMDA™
OJEMDA (tovorafenib) is a Type II RAF kinase inhibitor of mutant BRAF V600, wild-type BRAF, and wild-type CRAF kinases.
OJEMDA is indicated for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Tovorafenib was granted Breakthrough Therapy and Rare Pediatric Disease designations by the FDA for the treatment of patients with pLGG harboring an activating RAF alteration, and it was evaluated by the FDA under priority review. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma and from the European Commission for the treatment of glioma.
For more information, please visit www.ojemda.com.
About Day One Biopharmaceuticals
Day One Biopharmaceuticals believes when it comes to pediatric cancer, we can do better. The Company was founded to address a critical unmet need: the dire lack of therapeutic development in pediatric cancer. Inspired by “The Day One Talk” that physicians have with patients and their families about an initial cancer diagnosis and treatment plan, Day One aims to re-envision cancer drug development and redefine what’s possible for all people living with cancer—regardless of age—starting from Day One.
Day One partners with leading clinical oncologists, families, and scientists to identify, acquire, and develop important targeted cancer treatments. The Company’s pipeline includes tovorafenib (OJEMDA™), DAY301 and a VRK1 inhibitor program.
Day One is based in Brisbane, California. For more information, please visit www.dayonebio.com or find the Company on LinkedIn or X.
Day One uses its Investor Relations website (ir.dayonebio.com), its X handle (x.com/DayOneBio), and LinkedIn Home Page (linkedin.com/company/dayonebio) as a means of disseminating or providing notification of, among other things, news or announcements regarding its business or financial performance, investor events, press releases, and earnings releases, and as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD.
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 and commercialize cancer therapies, expectations from current and planned
Exhibit 99.1
clinical trials, the execution of the Phase 2 and Phase 3 clinical trial for tovorafenib as designed, expectations with respect to the timing of Day One’s Phase 1a/b clinical trial of DAY301, any expectations about safety, efficacy, timing and ability to complete clinical trials, release data results and to obtain regulatory approvals for tovorafenib and other candidates in development, and the ability of tovorafenib to treat pLGG or related indications.
Statements including words such as “believe,” “plan,” “continue,” “expect,” “will,” “develop,” “signal,” “potential,” or “ongoing” and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements.
Forward-looking statements are subject to risks and uncertainties that may cause Day One’s actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties in this press release and other risks set forth in our filings with the Securities and Exchange Commission, including Day One’s ability to develop, obtain and retain regulatory approval for or commercialize any product candidate, Day One’s ability to protect intellectual property, the potential impact of global business or macroeconomic conditions, including as a result of inflation, rising interest rates, instability in the global banking system, geopolitical conflicts and the sufficiency of Day One’s cash, cash equivalents and investments to fund its operations. These forward-looking statements speak only as of the date hereof and Day One specifically disclaims any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law.
Exhibit 99.1
Day One Biopharmaceuticals, Inc.
Condensed Statements of Operations
(in thousands, except share and per share amounts)
(unaudited)
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Three Months Ended |
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Nine Months Ended |
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2024 |
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2023 |
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2024 |
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2023 |
Revenue: |
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Product revenue, net |
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$ 20,070 |
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$ — |
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$ 28,262 |
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$ — |
License revenue |
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73,691 |
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— |
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73,691 |
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— |
Total revenues |
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93,761 |
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— |
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101,953 |
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— |
Cost and operating expenses: |
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Cost of product revenue |
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1,590 |
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— |
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2,297 |
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— |
Research and development |
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33,563 |
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33,163 |
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165,879 |
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93,173 |
Selling, general and administrative |
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28,972 |
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18,275 |
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85,715 |
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53,374 |
Total cost and operating expenses |
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64,125 |
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51,438 |
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253,891 |
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146,547 |
Income (loss) from operations |
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29,636 |
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(51,438) |
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(151,938) |
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(146,547) |
Non-operating income: |
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Gain from sale of priority review voucher |
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— |
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— |
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108,000 |
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— |
Investment income, net |
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5,322 |
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5,291 |
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13,649 |
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12,163 |
Other income (expense), net |
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1,197 |
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(3) |
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1,177 |
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(22) |
Total non-operating income, net |
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6,519 |
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5,288 |
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122,826 |
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12,141 |
Income (loss) before income taxes |
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36,155 |
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(46,150) |
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(29,112) |
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(134,406) |
Income tax benefit (expense) |
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882 |
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— |
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(670) |
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— |
Net income (loss) |
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37,037 |
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(46,150) |
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(29,782) |
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(134,406) |
Net income (loss) per share - basic |
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$ 0.38 |
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$ (0.54) |
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$ (0.33) |
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$ (1.73) |
Net income (loss) per share - diluted |
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$ 0.38 |
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$ (0.54) |
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$ (0.33) |
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$ (1.73) |
Weighted-average number of common shares used in net income (loss) per share - basic |
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96,623,123 |
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85,952,501 |
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90,164,895 |
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77,682,237 |
Weighted-average number of common shares used in net income (loss) per share - diluted |
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96,937,759 |
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85,952,501 |
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90,164,895 |
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77,682,237 |
Day One Biopharmaceuticals, Inc.
Selected Condensed Balance Sheet Data
(in thousands)
(unaudited)
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September 30, |
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December 31, |
Cash, cash equivalents and short-term investments |
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$ 558,383 |
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$ 366,347 |
Total assets |
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600,807 |
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376,048 |
Total liabilities |
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45,344 |
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29,508 |
Accumulated deficit |
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(488,367) |
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(458,585) |
Total stockholders’ equity |
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555,463 |
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346,540 |
Exhibit 99.1
DAY ONE MEDIA
Laura Cooper, Head of Communications
media@dayonebio.com
DAY ONE INVESTORS
LifeSci Advisors, PJ Kelleher
pkelleher@lifesciadvisors.com
#####
Third Quarter 2024 Financial Results and Corporate Progress October 2024 Nasdaq: DAWN
Forward-Looking Statements 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, the anticipated gross proceeds of our private placement offering, timing and success of our commercialization and marketing efforts, 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 products and product candidates, the ability of OJEMDA™ (tovorafenib) to treat pediatric low-grade glioma (pLGG) or related indications, the potential therapeutic benefits and economic value of our products and product candidates, potential growth opportunities, competitive position, industry environment and potential market opportunities, our ability to protect intellectual property and the impact of global business or macroeconomic conditions, including as a result of inflation, changing interest rates, cybersecurity incidents, potential instability in the global banking system, changes in the U.S. presidential administration, uncertainty with respect to the federal debt ceiling and budget and potential government shutdowns related thereto and global regional conflicts, on our business and operations. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. These factors, together with those that are described under the heading “Risk Factors” contained in our most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and other documents we file from time to time with the SEC, may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and although we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted a thorough inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements. Furthermore, if our forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk.
Agenda & Day One Participants Opening Remarks Jeremy Bender (Chief Executive Officer) OJEMDATM (tovorafenib) Lauren Merendino (Chief Commercial Officer) Financial Performance Charles York (Chief Operating Officer & Chief Financial Officer) Q&A Session All, joined by: Sam Blackman (Co-Founder & Head of R&D)
Opening Remarks Jeremy Bender Chief Executive Officer
Executing On Our Priorities As A Commercial-Stage Company 1 Represents cash, cash equivalents and short-term investments as of September 30, 2024. OJEMDA $20.1M in net product revenue +145% quarter over quarter growth Steady cadence of new patient starts and favorable payer access Pipeline Progress Continued focus on fully enrolling frontline FIREFLY-2 trial Urgently working to initiate DAY301 Phase 1a trial, our potential first-in-class ADC targeting PTK-7 Financial Position Strong financial position with $558.4M in cash1 Building a Sustainable Company with Durable Growth for the Near and Long Term
OJEMDA Launch Performance Lauren Merendino Chief Commercial Officer
Impressive Performance on Multiple Fronts 1 OJEMDA received U.S. FDA accelerated approval for relapsed or refractory BRAF-altered pediatric low-grade glioma on April 23, 2024. 2 Cumulative prescriptions are approximations based on data available on September 30, 2024. $28.3M NET REVENUES SINCE LAUNCH1 855 CUMULATIVE PRESCRIPTIONS SINCE LAUNCH1,2 ~80% PAYER APPROVAL RATE
Quarterly Net Revenue OJEMDA Patient Demand Continues to Drive Growth $8.2M $20.1M +145% Revenue Drivers Consistent patient demand & high continuation rates were primary growth drivers in Q3 The growth rate reflects ongoing adoption of OJEMDA by physicians, payers, and patients. High payer approval rates $28.3M Net Revenue Since Launch
Strong Growth in Prescriptions in 3Q 2024 1 Total prescriptions includes prescriptions for all patients (new & refill, paid & free drug and on-label & off-label patients). 2 Prescriptions are approximations based on data available on September 30, 2024. HCP – Health Care Professional. 239 619 +159% Quarterly U.S. OJEMDA Prescriptions (TRx)1,2 Breadth of Prescribers & Patients Nearly doubled the number of HCPs who prescribed OJEMDA HCPs treating more than 1 patient continues to increase Significant uptake in both fusion & mutation patients and broad range of tumor locations in the brain Continued positive feedback from physicians and a desire to use more OJEMDA
Physician Perspectives Momentum Continues to Build in Physicians Treating pLGG 1 Day One Market Research, survey of 24 pLGG-treating Oncologiists. 2 Day One prescription data. 3 Guidepoints interview, 10/14/2024, 4 Day One Market Research. “From what I recall, over 80% of patients achieved at least stable disease and about 50%, had significant tumor shrinkage. That’s exciting when you compare it to where we’ve been in the past.” 4 “Now, our paradigm is, you get your traditional chemotherapy as your upfront. Then if you progress, you have a choice between a MEK inhibitor and tovorafenib…I think it's going to be mostly patients choosing Tovo over MEK. I also think that there's going to be patients who progress on MEK inhibitor that will go on Tovo.” 3 - Neuro-Oncologist KOL Feedback from pLGG Treaters 100% AWARENESS OF OJEMDA1 >90% INTEND TO PRESCRIBE OJEMDA1 >80% TOP TIER ACCOUNTS HAVE STARTED ONE OR MORE PATIENTS ON OJEMDA2
Significant Progress on Payer Coverage, with Published Coverage for the Majority of Patients ~60% Commercial Patients 1 Breakaway Partners LLC – Breakaway Partners Analytics Platform. Metrics Based on 190.5M Commercial Lives . 2 Artia Solutions - Medicaid Coverage Status Report and Breakaway Partners LLC – Breakaway Partners Analytics Platform. Metrics Based on 74.9M Total Medicaid Lives. 3 Internal prescription data. ~80% Patients Approved for Coverage, Despite Lower Reported Coverage3 PAYER MIX ~40% Medicaid Patients Commercial Reported Coverage1 Percent of Covered Lives Medicaid Reported Coverage2 Percent of Covered Lives Covered 67% (+17%) Covered 62% (+48%) Not Covered Pending Review 4% Not Covered Pending Review 3% Not Published 35% Not Published 29%
Well-Positioned For Continuing Commercial Execution And Sustained Growth Continuing Launch Trajectory Increase breadth & depth of prescribers Position OJEMDA as the standard of care in 2nd line Establish remaining payer coverage policies
Financial Performance Charles York Chief Operating Officer and Chief Financial Officer
Third Quarter 2024 Financial Results All financial information is unaudited. 1 Includes stock-based compensation expense of $3.8 million and $13.2 million for the three and nine months ended 9/30/24, and $3.3 million and $10.1 million for the three and nine months ended 9/30/23, respectively. 2 Includes stock-based compensation expense of $7.8 million and $24.0 million for the three and nine months ended 9/30/24, and $6.3 million and $18.4 million for the three and nine months ended 9/30/23, respectively. 3 Includes sale of Priority Review Voucher of $108.0 million for the nine months ended 9/30/24. Financial Summary ($ in millions) Three Months Ended 9/30/24 Three Months Ended 9/30/23 Nine Months Ended 9/30/24 Nine Months Ended 9/30/23 OJEMDA Net Revenue 20.1 -- 28.3 -- License Revenue 73.7 -- 73.7 -- Total Revenue $93.8 $-- $101.1 $-- Cost of Product Revenue 1.6 -- 2.3 -- Research and Development Expense1 33.6 33.2 165.9 93.2 Selling, General and Administrative Expense2 29.0 18.3 85.7 53.4 Total Cost and Operating Expenses $64.1 $51.4 $253.9 $146.5 Non-operating Income3 6.5 5.3 122.8 12.1 Income Tax Benefit (Expense) 0.9 -- (0.7) -- Net Income (Loss) $37.0 ($46.2) ($29.8) ($134.4) 9/30/24 9/30/23 Cash, cash equivalents and short-term investments $558.4 $405.5
Thank You Nasdaq: DAWN
Day One Biopharmaceuticals Targeted Therapies for People of All Ages October 2024
Disclaimer This presentation and the accompanying oral commentary contain forward-looking statements that are based on our management’s beliefs and assumptions and on information currently available to our management. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “could,” “expect,” “plan,” anticipate,” “believe,” “estimate,” “predict,” “intend,” “potential,” “would,” “continue,” “ongoing” or the negative of these terms or other comparable terminology. Forward-looking statements include all statements other than statements of historical fact contained in this presentation, including information concerning our future financial performance, including the sufficiency of our cash, cash equivalents and short-term investments to fund our operations, business plans and objectives, the anticipated gross proceeds of our private placement offering, timing and success of our commercialization and marketing efforts, 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 products and product candidates, the ability of OJEMDA™ (tovorafenib) to treat pediatric low-grade glioma (pLGG) or related indications, the potential therapeutic benefits and economic value of our products and product candidates, potential growth opportunities, competitive position, industry environment and potential market opportunities, our ability to protect intellectual property and the impact of global business or macroeconomic conditions, including as a result of inflation, changing interest rates, cybersecurity incidents, potential instability in the global banking system, changes in the U.S. presidential administration, uncertainty with respect to the federal debt ceiling and budget and potential government shutdowns related thereto and global regional conflicts, on our business and operations. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. These factors, together with those that are described under the heading “Risk Factors” contained in our most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and other documents we file from time to time with the SEC, may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and although we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted a thorough inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements. Furthermore, if our forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk.
Cancer Therapies for People of All Ages Develop medicines for genomically-defined cancers Establish first-in-class position through rapid registration pathways Expand to adolescent and adult populations in parallel and pursue those opportunities with the same commitment we do for children Our Approach Nasdaq: DAWN IPO: 2021 Founded: 2018
1 OJEMDA has received accelerated approval by the U.S. Food and Drug Administration. 2 FIREFLY-1 is an open-label, pivotal Phase 2 trial. 3Ex-U.S. license agreement with Ipsen to commercialize OJEMDA (tovorafenib) outside the U.S. DAY301 is a license agreement with MabCare Therapeutics for exclusive worldwide rights, excluding Greater China, for MTX-13/CB-002, a novel ADC targeting PTK7. pLGG, pediatric low-grade glioma. VRK1 Program is a research collaboration and license agreement with Sprint Bioscience AB for exclusive worldwide rights to a research-stage program targeting VRK1. The safety and efficacy of investigational agents and/or investigational uses of approved products have not been established. Our Pipeline Product Candidate Therapeutic Area Preclinical Phase 1 Phase 2 Phase 3/ Registrational Approved Recent & Anticipated Milestones Tovorafenib3 Type II RAF Inhibitor OJEMDA brand name in U.S.1 Ex-U.S. Rights: BRAF-altered relapsed pLGG FDA approval April 2024 Ex-U.S. license agreement July 2024 Frontline RAF-altered pLGG First patient dosed March 2023 DAY301 PTK7 Targeted ADC Adult and pediatric solid tumors U.S. IND cleared April 2024 First patient dosed expected 4Q 2024 / 1Q 2025 VRK1 Program VRK1 Inhibitor Adult and pediatric cancers In-licensed August 2023 FIREFLY-1 (pivotal Phase 2)2 FIREFLY-2 (pivotal Phase 3)
OJEMDATM (tovorafenib) Relapsed or Refractory BRAF-altered pLGG
Pediatric Low-Grade Glioma: 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 term1 A Serious and Life-Threatening Disease For the majority of pLGG patients in the relapsed setting, there is no standard of care and no approved therapies Up to 75% of pLGGs have a BRAF alteration*, of those ~80% are BRAF fusions and ~20% are BRAF V600 mutations2-6 Despite surgery playing a significant role in treatment, the vast majority of patients still require systemic therapy7,8 Due to high rate of disease recurrence, most patients will undergo multiple lines of systemic therapy over the course of their disease *Incidence of BRAF alterations varies across pLGG subtypes. 1 Sievert AJ, Fisher MJ. Pediatric low-grade gliomas. J Child Neurol. 2009;24(11):1397-1408. doi:10.1177/0883073809342005. 2 Penman CL et al. Front Oncol. 2015;5:54. 3 Cohen AR., N Engl J Med. 2020;386(20):1922-1931. 4 Lassaletta A, et al. J Clin Oncol. 2017;35(25):2934-2941. 5 Faulkner C, et al. J Neuropathol Exp Neurol. 2015;74(9):867-872. 6 Packer RJ, et al. Neuro Oncol. 2017;19(6):750-761. 7 Ostrum QT et al., Neuro Oncol. 2015; 16(Suppl 10):x1-x36; 8 De Blank P. et al., Curr Opin Pediatr. 2019 Feb; 31(1):21-27.
Source: 1. Heitzer AM, Raghubar K, Ris MD, et al. Neuropsychological functioning following surgery for pediatric low-grade glioma: a prospective longitudinal study. J Neurosurg Pediatr. 2019;1-9. doi:10.3171/2019.9.PEDS19357. 2. Bryant R. Managing side effects of childhood cancer treatment. J Pediatr Nurs. 2003;18(2):113-125. doi:10.1053/jpdn.2003.11. 3. Zahnreich S, Schmidberger H. Childhood cancer: occurrence, treatment and risk of second primary malignancies. Cancers (Basel). 2021;13(11):2607. doi:10.3390/cancers/13112607. 4. National Cancer Institute. Fertility issues in girls and women with cancer. http://www.cancer.gov. Accessed June 13, 2022. 5. Alessi I., Caroleo A.M., de Palma L., Mastronuzzi A., Pro S., Colafati G.S., Boni A., Della Vecchia N., Velardi M., Evangelisti M., et al. Short and Long-Term Toxicity in Pediatric Cancer Treatment: Central Nervous System Damage. Cancers. 2022;14:1540. doi: 10.3390/cancers14061540. Conventional Treatments Can Be Disruptive To Childhood And Can Have Significant Long-Term Consequences Goal of therapy is to control the tumor, minimize the burden of surgery, chemotherapy, and radiation, and reduce the risk of life-long treatment and disease-related effects Significant recovery times Risks of complications Resection may be limited by location of tumor Potential for functional deficits based on location of tumor and extent of resection Risk of secondary malignancy Risk of malignant transformation Risk of vascular proliferation and stroke Neurocognitive impact, depending on location of tumor and radiation field Requirement for indwelling catheter and weekly infusions Risk of neutropenia, hypersensitivity reactions, nausea and vomiting and peripheral neuropathy Surgery Chemotherapy Radiation
Overview U.S. Prescribing Information For OJEMDATM (tovorafenib) *This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial. INDICATION OJEMDA is indicated for the treatment of pediatric patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma harboring a BRAF fusion or rearrangement, or BRAF V600 mutation RECOMMENDED DOSE 380 mg/m2 administered orally once weekly (not to exceed a dose of 600mg once weekly); OJEMDA can be taken with or without food For full prescribing information, visit dayonebio.com Available in tablet formulation and pediatric-friendly powder for oral suspension
Efficacy Summary From OJEMDATM (tovorafenib) Prescribing Information Overall response rate (RAPNO-LGG) in 76 evaluable patients 51% Response (IRC) RAPNO-LGG n n (%) 95% CI ORR, n (%) BRAF fusion or rearrangement BRAF V600 mutation Prior MAPKi use MAPKi-naïve Median DOR, months Median TTR, months Range 76 64 12 45 31 39 39 39 (51) 33 (52) 6 (50) 22 (49) 17 (55) 13.8 5.3 1.6-11.2 40-63 39-64 21-79 31-64 36-73 11.3-NR† Maximum change in tumor size (%) June 5, 2023 data cutoff. CI, confidence interval; DOR, duration of response; IRC, independent radiology review committee; LGG, low-grade glioma; NR, not reached; ORR, overall response rate; RAPNO, Response Assessment in Pediatric Neuro-Oncology; TTR, time to response; CR, complete response; PR, partial response; MR, minor response; SD, stable disease; PD, progressive disease. † As of the data cutoff, 66% remain on tovorafenib.
Warnings and Precautions Hemorrhage Skin toxicity, including photosensitivity Hepatotoxicity Effect on growth Embryo-fetal toxicity Use in NF1- associated tumors Safety Summary From OJEMDATM (tovorafenib) Prescribing Information No boxed warnings or contraindications TEAEs (≥ 30% of patients [n=137]) Preferred Term, n (%) Any Grade Grade ≥3 Any AE 137 (100) 86 (63) Hair color changes 104 (76) 0 Anemia 81 (59) 15 (11) Elevated CPK 80 (58) 16 (12) Fatigue 76 (55) 6 (4) Vomiting 68 (50) 6 (4) Hypophosphatemia 64 (47) 0 Headache 61 (45) 2 (1) Maculo-papular rash 60 (44) 11 (8) Pyrexia 53 (39) 5 (4) Dry skin 49 (36) 0 Elevated LDH 48 (35) 0 Increased AST 47 (34) 4 (3) Constipation 45 (33) 0 Nausea 45 (33) 0 Upper RTI 43 (31) 2 (1) Dermatitis acneiform 42 (31) 1 (1) Epistaxis 42 (31) 1 (1) June 5, 2023 data cutoff. OJEMDA safety data (n=137). Treatment-emergent AEs ≥20% any grade in arms 1 & 2. AE, adverse event; AST, aspartate aminotransferase; CPK, creatine phosphokinase; LDH, lactate dehydrogenase; RTI, respiratory tract infection; TEAEs, treatment-emergent adverse events.
Addressable U.S. Opportunity of OJEMDA Estimated to be ~2,000-3,000 Patients Incident Therapeutic Build for New pLGG Patients to be Treated in Frontline Setting U.S. Incident Patients <25 years old with CNS Tumors (0.00521%)1,2 ~5,500 Rate of Low Grade Gliomas (Gliomas rate 63%, Low-Grade 77%)2 ~2,600 ~1,500 Patients Ineligible for Surgery or Post Surgery (58%)2 ~1,100 % BRAF Fusion (80%) † % BRAF V600 (20%) † † ~880 ~220 Frontline (1L) Annual Incident Patients ~1,100 1L BRAF-Altered pLGG Patients Eligible for Systemic Therapy Illustrative pLGG Patient Flow§ 5 Year Prevalence ~5,500 Progressed After 5 Years ~55% Relapsed / Refractory (2L+) ~55-60% 1. US Census. 2 CBTRUS, Qaddoumi et al 2009, Schreck et al 2019, ClearView Analysis. 3 Penman CL et al. Front Oncol. 2015;5:54. 4 Cohen AR., N Engl J Med. 2020;386(20):1922-1931. 5 Lassaletta A, et al. J Clin Oncol. 2017;35(25):2934-2941. 6 Faulkner C, et al. J Neuropathol Exp Neurol. 2015;74(9):867-872. 7 Packer RJ, et al. Neuro Oncol. 2017;19(6):750-761. * Incidence of BRAF alterations varies across pLGG subtypes. † Predominantly seen in pilocytic astrocytomas. †† May vary across pLGG subtypes. BRAF, V-Raf murine sarcoma viral oncogene homolog B; MAPK, mitogen-activated protein kinase; pLGG, pediatric low-grade glioma. § Estimated annual incidence, estimated prevalence, estimated progression rates, and estimated recurrent/progressive total addressable opportunity are Day One calculations based on publicly available data. The estimated recurrent/progressive total addressable opportunity is based on progression free survival curves modeled from published literature and internal market research conducted by EpidStrategies, A Division of ToxStrategies, Inc. on behalf of Day One. Majority of pLGG patients will progress within 5 years OJEMDA’s Addressable Opportunity in the U.S. Rate of BRAF-Altered (70%-75%)3-7* Prevalence Under 25 years ~26,000 Treated Population ~2,000-3,000 Recurrences Trigger Entry to Treated Population
Product Profile Aligns With What Physicians Are Looking For In A Therapy Data from Pivotal Phase 2 FIREFLY-1 trial. Meaningful tumor stabilization or shrinkage may be possible with OJEMDA. In the clinical trial: 51% of children experienced tumor shrinkage by at least 25% 82% of children saw their tumors shrink or remain stable Efficacy Safety Dosing Generally well-tolerated therapy, with 9 out of 10 patients staying on treatment in the clinical trial Most common grade 3 / 4 adverse events include: anemia, elevated CPK, maculo-papular rash, fatigue & vomiting Once-weekly, taken with or without food conveniently from home can mean fewer daily interruptions OJEMDA is indicated for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion, rearrangement, or BRAF V600 mutation.
Strong Q3 Patient Demand Continues to Drive Performance HCP, Health Care Professional. * Total prescriptions includes prescriptions for all patients (new & refill, paid & free drug and on-label & off-label patients), prescriptions are approximations based on data available on September 30, 2024. Strong and steady patient demand & high continuation rates were primary growth drivers in Q3 2024 Revenue Drivers Breadth & Depth of Prescribers Growing Utilization High payer approval rate enabling a high percentage of patients on paid drug Payer Coverage $20.1M in net product revenue in 3Q 2024 619 prescriptions in Q3 2024, 159% growth vs Q2 2024* Nearly doubled the number of HCPs who prescribed OJEMDA in Q3 HCPs treating more than 1 patient continues to increase
Coverage Approval Rates are High Across both Commercial and Medicaid Payers Despite Limited Published Coverage Reported Coverage1,2 Percent of Covered Lives 1 Breakaway Partners LLC – Breakaway Partners Analytics Platform. Metrics Based on 190.5M Commercial Lives . 2 Artia Solutions - Medicaid Coverage Status Report and Breakaway Partners LLC – Breakaway Partners Analytics Platform. Metrics Based on 73.9M Total Medicaid Lives. 3 Internal prescription data. Data source date 9/30/2024. Coverage comparison data 9/30/2024 vs. 6/30/24. Covered ~64% (+40%) Not Covered Pending Review 3% Not Published 33% Payer Mix ~60% commercial patients ~40% Medicaid patients ~80% Patients Approved for Coverage, Despite Lower Reported Coverage3
Well-Positioned For Commercial Execution And Sustained Growth Continuing Launch Trajectory Increase breadth & depth of prescribers Position OJEMDA as the standard of care in 2nd line Establish remaining payer coverage policies
FIREFLY-2 / LOGGIC Pivotal Phase 3 Trial of Tovorafenib in Frontline pLGG
FIREFLY-2/LOGGIC Pivotal Phase 3 Trial Of Tovorafenib In Frontline pLGG Trial Design * COG or SIOPe-LGG regimen. Abbreviations: CHG, chiasmatic, hypothalamic glioma; DoR, duration of response; LGG, low-grade glioma; ORR, objective response rate; QoL, quality of life; QW, once weekly; SoC, standard of care. Endpoints Randomized, global, registrational Phase 3 trial of monotherapy tovorafenib vs SoC chemotherapy Eligibility: Patients aged 6 months to <25 years with LGG harboring a RAF alteration and requiring first-line systemic therapy Tovorafenib available as tablets and pediatric-friendly liquid suspension Patients who progress after stopping tovorafenib may be re-challenged Patients who progress in the SoC arm during or post-treatment may cross-over to receive tovorafenib Primary endpoint: ORR based on RAPNO-LGG criteria, assessed by blinded independent central review The ORR primary analysis is expected to occur ~12 months after the last patient randomized Key secondary endpoints: PFS and DoR by RAPNO-LGG criteria Other secondary endpoints: changes in neurological and visual function, safety, and tolerability Key exploratory objectives: QoL and health utilization measures Non-resectable or sub-total resected LGG AND Requiring first-line systemic therapy N ≈ 400 Stratified by Location of tumor Genomic alteration CDKN2A status Infant CHG diagnosis Tovorafenib, 380mg/m2 QW (not to exceed 600 mg) Investigator's choice of vincristine/carboplatin* or vinblastine or monthly carboplatin Long-term follow-up (48 months) 1:1 Randomization
DAY301 PTK7 Targeted Antibody Drug Conjugate (ADC)
DAY301: Next Generation ADC Targeting PTK7 1 Cho BC, et al. Ann Oncol. (34; Suppl 2): S460-S461, 2023. PTK7: Clinically-Validated ADC Target DAY301: Potential First-in-Class Asset Substantial Development and Commercial Opportunities for DAY301 Anti-tumor activity of anti-PTK7 ADC demonstrated in Phase 1b trial of Pfizer / Abbvie’s cofetuzumab pelidotin1 High PTK7 expression in multiple adult and pediatric tumor histologies U.S. IND Cleared – Target First Patient Dosed in Q4 2024 / Q1 2025 Novel ADC active in preclinical models, designed to maximize therapeutic window
PTK7: A Clinically-Validated ADC Target 1 Phase 1b study of PF-06647020/ABBV-647. Potential opportunity for a next-generation PTK7 ADC with improved therapeutic index Clinical results for cofetuzumab pelidotin1 demonstrated proof of concept for PTK7-targeted ADCs Cofetuzumab pelidotin activity seen in multiple tumor types: Ovarian (Pt-resistant): ORR 27% (n=63) TNBC: ORR 21% (n=29) NSCLC: ORR 19% (n=31) mDOR: 4.2-5.7m for Ovarian (Pt-resistant)/TNBC/NSCLC mPFS: 1.5-2.9m for Ovarian (Pt-resistant)/TNBC/NSCLC Aur0101 program limited by toxicity, resulting in reduced dose intensity and duration A next generation product with optimized properties and a better therapeutic index may achieve greater clinical efficacy
DAY301: Potential First-In-Class Asset 1) Damelin M, et al. A PTK7-targeted antibody-drug conjugate reduces tumor-initiating cells and induces sustained tumor regressions. Sci Transl Med. 2017. HNSTD, Highest Non-Severely Toxic Dose; P-gp, P-glycoprotein. DAY301 has been designed to maximize therapeutic index and overcome limitations of prior programs Tumor regression at tolerable doses seen in multiple preclinical models Higher HNSTD in cyno toxicology studies; payload with known safety profile High cell permeability / bystander effect; low efflux (not a P-gp substrate) Novel, highly hydrophilic, cleavable linker Moderate-to-high affinity antibody with favorable stability and developability profile Drug-antibody-ratio (DAR) of 8, shown to be effective for other ADCs in solid tumors IP: Composition of Matter patent term expected 2044, once issued DAY301
DAY301: First-in-Class Potential PDX 362310 TNBC H-score 255 PDX 362797 SCLC H-score 210 PDX LD1-200615 HNSCC H-score 120 0 1,000 2,000 3,000 0 20 40 60 80 Tumor Volume (mm3) (Mean ± SEM) Days Post Administration 0 1,000 2,000 3,000 4,000 0 7 14 21 28 Tumor Volume (mm3) (Mean ± SEM) Days Post Administration *P 0.0435 0 400 800 1,200 1,600 2,000 2,400 0 7 14 21 28 35 *P 0.0316 Tumor Volume (mm3) (Mean ± SEM) Days Post Administration Control antibody + DAY301 payload Vehicle Control antibody + auristatin payload Cofetuzumab pelidotin, 5 mg/kg DAY301, 10 mg/kg Ref: Kong C, et al. MTX-13, a Novel PTK7-Directed Antibody–Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors. Mol Cancer Ther. 2023 Control antibody + auristatin payload, 5 mg/kg Cofetuzumab pelidotin, 5 mg/kg Control antibody + DAY301 payload, 10 mg/kg Cofetuzumab mAb + DAY301 payload, 10 mg/kg DAY301, 5 mg/kg DAY301, 10 mg/kg Vehicle Cofetuzumab pelidotin, 10 mg/kg Chemotherapy control Cofetuzumab mAb + DAY301 payload Control antibody + DAY301 payload Anti-DLL3 mAb + DAY301 payload, 10 mg/kg B7-H3 DXd ADC, 10 mg/kg DAY301, 10 mg/kg Indicates when drug was administered Improved tumor regression activity demonstrated for DAY301 vs. benchmarks in multiple preclinical models
DAY301: Encouraging Development And Commercial Opportunities Indication PTK7 Expression (>1+) U.S. Patient Population Cases/deaths ORR at Relapse Median OS at Relapse Endometrial 100%2 67,880/13,2503 39%7 9 months7 Esophageal SCC 76%1 22,370/16,1303 5%4 3 months4 Gastric 35%2 26,890/10,8803 12%14 6-14 months15 Head & Neck SCC 75%1 54,540/11,5803 32%5 7.8 months5 NSCLC 50%2 199,393/106,3103 45-60%8 7-12 months9 Ovarian (platinum resistant) 30%2 (95%)* 19,710/13,2703 20-35%3 17.2 months6 Small Cell Lung 50%2 35,187/18,7603 10-40%10 9-12 months11 TNBC 70%2 310, 720/42,2503 5-35%12 28 months13 Potential pediatric indications include: neuroblastoma, rhabdomyosarcoma and osteosarcoma 1 Kong et al, 2023; 2 Protein Atlas; 3 PDQ; 4 Parry et al, 2015; 5 Vermorken et al, 2010; 6 Sehouli et al, 2008; 7 Rutten et al, 2021; 8 Park et al, 2017; 9 Assi et al, 2023; 10 Abughanimeh et al, 2020; 11 Asai et al, 2014; 12 Bardia et al, 2021; 13 Cai et al, 2023; 14 Sym et al, 2008; 15 Ji et al, 2023. * MabCare data
DAY301-001: Initial Phase 1a/b Clinical Trial Design DL, Dose Level; RD, Recommended Dose; BOIN, Bayesian Optimal Interval; HNSCC, Head and Neck Squamous Cell Carcinoma; SCLC, Small Cell Lung Cancer; SCC, Squamous-Cell Carcinoma; NSCLC, Non-Small Cell Lung Cancer Phase 1a: Monotherapy Dose Escalation FDA-cleared starting dose DL5 RD1 RD2 Identify two recommended dose levels for further evaluation, based on safety and anti-tumor activity BOIN design for efficiency of dose escalation Backfill active dose levels to generate additional safety data Enroll tumor types with known high PTK7 expression Advance two recommended dose levels to Phase 1b Final dose optimization scheme and approval path pending discussions with FDA at end of dose escalation RD1 Simon 2-stage design Expand to a potential single-arm registrational trial for accelerated approval or randomized trial at optimized dose RD1 cohort RD2 cohort Go to dose optimization Phase 1b: Monotherapy Dose Expansion and Optimization Phase 1: Pediatric Monotherapy Dose Confirmation RD-1 RD2 Lower of the two adult RDs Potential adult indications include platinum resistant ovarian cancer, squamous NSCLC, esophageal SCC, HNSCC, endometrial, and/or SCLC Patients to be selected based on PTK7 expression clinical trial assay Pediatric dose confirmation and efficacy assessment to begin near/at the end of adult dose escalation Initial target indications include neuroblastoma, osteosarcoma, rhabdomyosarcoma Key Design Elements Adult & Pediatric Development DL4 DL3 DL2 DL1 RD1
Summary
Third Quarter 2024 Financial Results All financial information is unaudited. 1 Includes stock-based compensation expense of $3.8 million and $13.2 million for the three and nine months ended 9/30/24, and $3.3 million and $10.1 million for the three and nine months ended 9/30/23, respectively. 2 Includes stock-based compensation expense of $7.8 million and $24.0 million for the three and nine months ended 9/30/24, and $6.3 million and $18.4 million for the three and nine months ended 9/30/23, respectively. 3 Includes sale of Priority Review Voucher of $108.0 million for the nine months ended 9/30/24. Financial Summary ($ in millions) Three Months Ended 9/30/24 Three Months Ended 9/30/23 Nine Months Ended 9/30/24 Nine Months Ended 9/30/23 OJEMDA Net Revenue 20.1 -- 28.3 -- License Revenue 73.7 -- 73.7 -- Total Revenue $93.8 $-- $101.1 $-- Cost of Product Revenue 1.6 -- 2.3 -- Research and Development Expense1 33.6 33.2 165.9 93.2 Selling, General and Administrative Expense2 29.0 18.3 85.7 53.4 Total Cost and Operating Expenses $64.1 $51.4 $253.9 $146.5 Non-operating Income3 6.5 5.3 122.8 12.1 Income Tax Benefit (Expense) 0.9 -- (0.7) -- Net Income (Loss) $37.0 ($46.2) ($29.8) ($134.4) 9/30/24 9/30/23 Cash, cash equivalents and short-term investments $558.4 $405.5
Priorities as a Commercial-Stage Company Expand awareness amongst physicians and establish broad coverage to enable patient access Establish OJEMDA as the standard of care for relapsed or refractory pLGG harboring a BRAF alteration Provide a positive and supportive experience when initiating OJEMDA therapy for patients and families Grow Day One into a leading, biopharmaceutical company that is the partner of choice for oncology drug development Explore selective partnerships as a source of capital and risk sharing Further invest in business development activities to expand our multiple asset portfolio for both children and adults FIREFLY-2: Study tovorafenib as a frontline therapy for treatment-naive patients with pLGG Develop DAY301, ADC targeting PTK7 in pediatric and adult solid tumors Advance early stage VRK1 program to clinical development Launch OJEMDATM (tovorafenib) Advance Portfolio Expand Pipeline
Appendix
Tovorafenib Inhibits Both BRAF Fusions And BRAF V600 Mutations Tovorafenib is an investigational, oral, selective, CNS-penetrant, type II RAF inhibitor that was designed to inhibit both monomeric and dimeric RAF kinase Activity in tumors driven by both RAF fusions and BRAF V600E mutations Tablet and pediatric-friendly liquid suspension Once weekly dosing Currently approved type I BRAF inhibitors are indicated for use in patients with tumors bearing BRAF V600 mutations Type I BRAF inhibitors cause paradoxical MAPK activation in the setting of wild-type RAF, increasing the risk of tumor growth in BRAF fusion-driven Source: 1. Sun Y et al., Neuro Oncol. 2017; 19: 774–85; 2. Sievart AJ et al., PNAS. 2013; 110:5957-62; 3. Karajannis MA et al., Neuro Oncol 2014;16(10):1408-16. RAS-independent activation of the MAPK pathway MAPK pathway RAS RAF MEK ERK Proliferation and survival RAF mutation RAF fusion Proliferation and survival Proliferation and survival Tovorafenib
June 5, 2023 data cutoff. 1 Wen PY, et al. J Clin Oncol. 2010;28(11):1963-1972. 2 Fangusaro J, et al. Lancet Oncol. 2020;21(6):e305–316. 3 van den Bent MJ, et al. Lancet Oncol. 2011;12(6):583-593. Abbreviations: CBR, clinical benefit rate; IRC, independent review committee; C, cycle; D, day; LGG, low-grade glioma; ORR, objective response rate; PFS, progression-free survival; DoR, duration of response; QW, once weekly; TTR, time to response; RANO, Response Assessment in Neuro-Oncology; RAPNO, Response Assessment in Pediatric Neuro-Oncology; MAPK, mitogen-activated protein kinase. For more information, please refer to NCT04775485 Pivotal Phase 2 Trial Of Monotherapy Tovorafenib In Relapsed Or Progressive pLGG (FIREFLY-1) Trial Design Endpoints (Pivotal Arm 1) Three arm, open-label, global registrational phase 2 trial Pivotal Arm 1 (recurrent/progressive pLGG, n=77): harboring a KIAA1549-BRAF fusion or BRAF V600E mutation Arm 2 (expanded access recurrent/progressive LGG, n=60): harboring an activating RAF alteration Arm 3 (extracranial solid tumors): harboring an activating RAF fusion Primary endpoint: ORR based on RANO-HGG1, assessed by blinded independent central review Secondary endpoints: ORR by RAPNO-LGG2 assessed by blinded independent central review; PFS, DoR; TTR, CBR; safety Exploratory analyses: ORR and CBR by RANO-LGG3 assessed by blinded independent central review Day –28 to 0 Study Drug Administration 420mg/m2 QW (not to exceed 600mg), QW in 28-day cycles After Cycle 27: patients may either continue treatment or enter drug holiday period at any time (at discretion of investigator) Screening C27D1 Enrollment/ Baseline (C1D1) End of Trial Clinical and radiological evaluations at baseline, and every 3rd cycle for pLGG and every 2nd cycle for solid tumors Eligibility evaluation Treatment period: minimum of 2 years or until progression or toxicity/intolerability Key Inclusion Criteria 6 months – 25 years of age RAF-altered tumor ≥1 prior line of systemic therapy with radiographic progression Prior use of MAPK pathway targeted therapy was permitted
Data from Pivotal Phase 2 FIREFLY-1 Trial June 5, 2023 data cutoff
FIREFLY-1 Baseline Patient Characteristics June 5, 2023 data cutoff. *Includes 6 patients with BRAF duplication and 2 with BRAF rearrangement per fluorescence in situ hybridization or in situ hybridization. †Includes tumors that were extending into multiple regions of the brain, leptomeningeal disease, and/or spinal disease. ‡The 5 patients that had previously received both a MEK inhibitor and also a BRAF inhibitor are recorded in both the “Prior MEK inhibitor” and “Prior BRAF inhibitor” groups. MAPK, mitogen-activated protein kinase. Characteristic Arm 1 (n=77) Median age, years (range) 8 (2-21) Sex, n (%) Male Female 40 (52) 37 (48) Race, n (%) White Asian Black Multiple Other Not specified 41 (53) 5 (6) 2 (3) 3 (4) 6 (8) 20 (26) Number of lines of prior systemic therapy Median (range) 1, n (%) 2, n (%) ≥3, n (%) 3 (1-9) 17 (22) 21 (27) 39 (51) Prior MAPK pathway targeted therapy, n (%) Prior MEK inhibitor Prior BRAF inhibitor Prior BRAF and MEK inhibitors‡ Any MAPK inhibitor 43 (56) 8* (10) 5 (7) 46 (60) BRAF alteration (n=77) Location (n=77) Optic pathway 51% Cerebral hemisphere 8% Brain stem 8% Deep midline structures 12% Other 16%† Cerebellum 6% 17% 83%
Tumor Response To Tovorafenib Using RAPNO-LGG, RANO-LGG and RANO-HGG Maximum change in tumor size (%) Maximum change in tumor size (%) Maximum change in tumor size (%) RAPNO-LGG RANO-LGG RANO-HGG June 5, 2023 data cutoff. BOR, best overall response; CBR, clinical benefit rate; CI, confidence interval; CR, complete response; DOR, duration of response; HGG, high-grade glioma; IRC, independent radiology review committee; LGG, low-grade glioma; MR, minor response; n/a, not applicable; NE, not evaluable; NR, not reached; ORR, overall response rate; PD, progressive disease; PR, partial response; RANO, Response Assessment in Neuro-Oncology; RAPNO, Response Assessment in Pediatric Neuro-Oncology; SD, stable disease; TTR, time to response. * ORR, CBR and BOR for RAPNO-LGG and RANO-LGG included MRs. Response (IRC) RAPNO-LGG n=76 RANO-LGG N=76 RANO-HGG N=69 ORR,* n (%) 95% CI 39 (51) 40-63 40 (53) 41-64 46 (67) 54-78 CBR,* n (%) SD of any length of time SD ≥12 months 62 (82) 43 (57) 63 (83) 46 (61) 64 (93) 54 (78) BOR,* n (%) CR PR MR SD SD <12 months SD ≥12 months PD NE 0 28 (37) 11 (14) 23 (30) 19 (25) 4 (5) 13 (17) 1 (1) 0 20 (26) 20 (26) 23 (30) 17 (22) 6 (8) 11 (14) 2 (3) 12 (17) 34 (49) n/a 18 (26) 10 (14) 8 (12) 4 (6) 1 (1) Median DOR, months 95% CI 13.8 11.3-NR 14.4 11.0-NR 16.6 11.6-NR Median TTR, months Range 5.3 1.6-11.2 5.5 1.6-11.3 3.0 2.6-16.6
Duration Of Tovorafenib Therapy For All Patients With RAPNO-LGG Evaluable Lesions June 5, 2023 data cutoff. Patients Overall treatment duration (months) 5.3 Months 13.8 Months Median time to response Median duration of treatment
Duration Of Tovorafenib Therapy For All Patients With RANO-HGG Evaluable Lesions Patients Overall treatment duration (months) June 5, 2023 data cutoff. 3.0 Months 16.6 Months Median time to response Median duration of treatment
Duration Of Tovorafenib Therapy For All Patients With RANO-LGG Evaluable Lesions Patients Overall treatment duration (months) June 5, 2023 data cutoff. 5.5 Months 14.4 Months Median time to response Median duration of treatment
Tumor Response To Tovorafenib Across Three Assessment Criteria Were Consistent Across BRAF Fusion And Mutation Patients, and Patients With Prior MAPK Treatment June 5, 2023 data cutoff. 1 Fangusaro J, et al. Lancet Oncol. 2020;21(6):e305–316. 2 Fangusaro J, et al. Lancet Oncol. 2020;21(6):e305–316. 3 van den Bent MJ, et al. Lancet Oncol. 2011;12(6):583-593. 4. Wen PY, et al. J. Clin Oncol. 2017;35(21),2439-2449. * ORR, CBR for RAPNO-LGG and RANO-LGG included MRs. ** the 95% CI were calculated using Kaplan-Meier method. RAPNO-LGG2 RANO-LGG3,4 RANO-HGG1 Response (IRC) n n n ORR,* n (%) 76 39 (51) 76 40 (53) 69 46 (67) BRAF fusion 64 33 (52) 64 33 (52) 59 41 (69) BRAF mutation 12 6 (50) 12 7 (58) 10 5 (50) Prior MAPKi 45 22 (49) 45 23 (51) 41 29 (71) MAPKi-naive 31 17 (55) 31 17 (55) 28 17 (61) CBR,* n (%) (SD of any length of time) 76 62 (82) 76 63 (83) 69 64 (93) BRAF fusion 64 53 (83) 64 53 (83) 59 55 (93) BRAF mutation 12 9 (75) 12 10 (83) 10 9 (90) Prior MAPKi 45 38 (84) 45 38 (84) 41 37 (90) MAPKi-naive 31 24 (77) 31 25 (81) 28 27 (96) CBR,* n (%) (SD ≥12 months) 76 43 (57) 76 46 (61) 69 54 (78) BRAF fusion 64 37 (58) 64 39 (61) 59 49 (83) BRAF mutation 12 6 (50) 12 7 (58) 10 5 (50) Prior MAPKi 45 25 (56) 45 26 (58) 41 33 (80) MAPKi-naive 31 18 (58) 31 20 (65) 28 21 (75) Median DOR, months (95% CI)** 39 13.8 (11.3-NR) 40 14.4 (11.0-NR) 46 16.6 (11.6-NR) BRAF fusion 33 13.8 (11.3-NR) 33 16.3 (11.0-NR) 41 16.8 (11.6-NR) BRAF mutation 6 NR (8.4-NR) 7 12.0 (8.4-NR) 5 15.1 (8.3-NR) Prior MAPKi 22 13.8 (11.3-NR) 23 12.0 (8.5-NR) 29 15.1 (9.0-16.8) MAPKi-naive 17 NR (8.4-NR) 17 16.3 (8.4-NR) 17 NR (11.6-NR)
Tovorafenib Safety Data (n=137) June 5, 2023 data cutoff. Treatment-emergent AEs ≥25% any grade in arms 1 & 2. AE, adverse event; ALT, Alanine transaminase; AST, aspartate aminotransferase; COVID-19, Coronavirus disease 2019; CPK, creatine phosphokinase; LDH, lactate dehydrogenase; RTI, respiratory tract infection; TEAEs, treatment-emergent adverse events; TRAEs, treatment-related adverse events. TEAEs TRAEs Preferred Term, n (%) Any Grade Grade ≥3 Any Grade Grade ≥3 Any AE 137 (100) 86 (63) 134 (98) 58 (42) Hair color changes 104 (76) 0 104 (76) 0 Anemia 81 (59) 15 (11) 67 (49) 14 (10) Elevated CPK 80 (58) 16 (12) 77 (56) 16 (12) Fatigue 76 (55) 6 (4) 60 (44) 6 (4) Vomiting 68 (50) 6 (4) 28 (20) 3 (2) Hypophosphatemia 64 (47) 0 48 (35) 0 Headache 61 (45) 2 (1) 29 (21) 0 Maculo-papular rash 60 (44) 11 (8) 56 (41) 11 (8) Pyrexia 53 (39) 5 (4) 17 (12) 1 (1) Dry skin 49 (36) 0 45 (33) 0 Elevated LDH 48 (35) 0 42 (31) 0 Increased AST 47 (34) 4 (3) 41 (30) 4 (3) Constipation 45 (33) 0 31 (23) 0 Nausea 45 (33) 0 25 (18) 0 Upper RTI 43 (31) 2 (1) 2 (1) 0 Dermatitis acneiform 42 (31) 1 (1) 41 (30) 1 (1) Epistaxis 42 (31) 1 (1) 27 (20) 0 Decreased appetite 39 (28) 5 (4) 28 (20) 4 (3) Paronychia 36 (26) 2 (1) 32 (23) 2 (1) Pruritus 35 (26) 1 (1) 32 (23) 1 (1) COVID-19 34 (25) 0 0 0 The most common reasons for discontinuation were tumor hemorrhage (3 patients) and decrease in growth velocity (2 patients) 33 patients (24%) had TRAEs leading to dose reduction; 50 patients (37%) had TRAEs leading to dose interruption Median duration of dose interruption was 2 weeks 9 patients (7%) had TRAEs leading to discontinuation