MEK1 inhibitors(Dual specificity mitogen-activated protein kinase kinase 1 inhibitors), MEK2 inhibitors(Dual specificity mitogen-activated protein kinase kinase 2 inhibitors)

Therapeutic Areas

NeoplasmsEndocrinology and Metabolic DiseaseSkin and Musculoskeletal Diseases+ [1]

Active Indication

MelanomaOvarian Cancer

Inactive Indication

Acute Myeloid LeukemiaAdvanced Malignant Solid NeoplasmBorderline serous tumour of ovary+ [10]

Originator Organization

Santhera Pharmaceuticals (USA), Inc.

Active Organization

Santhera Pharmaceuticals (USA), Inc.

Inactive Organization

EMD Serono, Inc.Merck Serono SAMerck KGaA

+ [1]

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

Structure

Molecular FormulaC15H16ClFIN3O3

InChIKeyHIEXZUXKTABHCP-PPHPATTJSA-N

CAS Registry1236361-78-6

Clinical Trials associated with Pimasertib hydrochloride

NCT06208657 / RecruitingPhase 1/2IIT

Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer

A companion platform trial to test novel targeted agents based on the patient's tumor profile.

Start Date10 Jul 2024

Sponsor / Collaborator

Kazia Therapeutics Ltd.

[+4]

NCT04985604 / Active, not recruitingPhase 1/2

A Phase 1b/2, Open Label Study of DAY101 Monotherapy or Combination With Other Therapies for Patients With Recurrent, Progressive, or Refractory Solid Tumors Harboring MAPK Pathway Aberrations

This is a Phase 1b/2, multi-center, open label umbrella study of patients ≥12 years of age with recurrent, progressive, or refractory melanoma or other solid tumors with alterations in the key proteins of the RAS/RAF/MEK/ERK pathway, referred to as the MAPK pathway.

Start Date15 Jul 2021

Sponsor / Collaborator

Day One Biopharmaceuticals, Inc.

NCT04789668 / CompletedPhase 1/2IIT

Phase I/II Trial of BINTRAFUSP ALFA (M7824) and Pimasertib for Treatment of Intracranial Metastases

This phase I/II trial studies the best dose and effect of pimasertib in combination with bintrafusp alfa in treating patients with cancer that has spread to the brain (brain metastases). Immunotherapy with bintrafusp alfa, a bifunctional fusion protein composed of the monoclonal antibody anti-PD-L1 and TGF-beta, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pimasertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pimasertib and bintrafusp alfa may help to prevent or delay the cancer from progressing (getting worse) and/or coming back.

Start Date15 Jan 2021

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

100 Clinical Results associated with Pimasertib hydrochloride

100 Translational Medicine associated with Pimasertib hydrochloride

100 Patents (Medical) associated with Pimasertib hydrochloride

Literatures (Medical) associated with Pimasertib hydrochloride

01 Nov 2023·Anti-cancer agents in medicinal chemistry

In silico Screening and Validation of Achyranthes aspera as a Potential Inhibitor of BRAF and NRAS in Controlling Thyroid Cancer

Article

Author: Tasleem, Munazzah ; Alamri, Ahmad M ; Khan, Najeeb U ; Alkhilaiwi, Faris A

Background::

Thyroid carcinoma (THCA) is one of the most prevalent endocrine tumors, accounting for 3.4% of all cancers diagnosed annually. Single Nucleotide Polymorphisms (SNPs) are the most prevalent genetic variation associated with thyroid cancer. Understanding thyroid cancer genetics will enhance diagnosis, prognosis, and treatment.

Methods::

This TCGA-based study analyzes thyroid cancer-associated highly mutated genes through highly robust in silico techniques. Pathway, gene expression, and survival studies were performed on the top 10 highly mutated genes (BRAF, NRAS, TG, TTN, HRAS, MUC16, ZFHX3, CSMD2, EIFIAX, SPTA1). Novel natural compounds from Achyranthes aspera Linn were discovered to target two highly mutated genes. The natural compounds and synthetic drugs used to treat thyroid cancer were subjected to comparative molecular docking against BRAF and NRAS targets. The ADME characteristics of Achyranthes aspera Linn compounds were also investigated

Results::

The gene expression analysis revealed that the expression of ZFHX3, MCU16, EIF1AX, HRAS, and NRAS was up-regulated in tumor cells while BRAF, TTN, TG, CSMD2, and SPTA1 were down-regulated in tumor cells. In addition, the protein-protein interaction network demonstrated that HRAS, BRAF, NRAS, SPTA1, and TG proteins have strong interactions with each other as compared to other genes. The ADMET analysis shows that seven compounds have druglike properties. These compounds were further studied for molecular docking studies. The compounds MPHY012847, IMPHY005295, and IMPHY000939 show higher binding affinity with BRAF than pimasertib. In addition, IMPHY000939, IMPHY000303, IMPHY012847, and IMPHY005295 showed a better binding affinity with NRAS than Guanosine Triphosphate.

Conclusion::

The outcomes of docking experiments conducted on BRAF and NRAS provide insight into natural compounds with pharmacological characteristics. These findings indicate that natural compounds derived from plants as a more promising cancer treatment option. Thus, the results of docking investigations conducted on BRAF and NRAS substantiate the conclusions that the molecule possesses the most suited drug-like qualities. Compared to other compounds, natural compounds are superior, and they are also druggable. This demonstrates that natural plant compounds can be an excellent source of potential anti-cancer agents. The preclinical research will pave the road for a possible anti-cancer agent.

01 Sep 2023·Journal of cell communication and signaling

Three generations of mTOR kinase inhibitors in the activation of the apoptosis process in melanoma cells

Article

Author: Krawczyk, Agnieszka ; Ciolczyk-Wierzbica, Dorota ; Wierzbicki, Karol ; Zarzycka, Marta ; Zemanek, Grzegorz

Abstract:

Many signaling pathways are involved in the mammalian target of rapamycin (mTOR), and this serine/threonine kinase regulates the most important cellular processes such as cell proliferation, autophagy, and apoptosis. The subject of this research was the effect of protein kinase inhibitors involved in the AKT, MEK, and mTOR kinase signaling pathways on the expression of pro-survival proteins, activity of caspase-3, proliferation, and induction of apoptosis in melanoma cells. The following inhibitors were used: protein kinase inhibitors such as AKT—MK-2206, MEK—AS-703026, mTOR—everolimus and Torkinib, as well as dual PI3K and mTOR inhibitor—BEZ-235 and Omipalisib, and mTOR1/2—OSI-027 inhibitor in single-mode and their combinations with MEK1/2 kinase inhibitor AS-703026. The obtained results confirm the synergistic effect of nanomolar concentrations of mTOR inhibitors, especially the dual PI3K and mTOR inhibitors (Omipalisib, BEZ-235) in combination with the MAP kinase inhibitor (AS-703026) in the activation of caspase 3, induction of apoptosis, and inhibition of proliferation in melanoma cell lines. Our previous and current studies confirm the importance of the mTOR signal transduction pathway in the neoplastic transformation process. Melanoma is a case of a very heterogeneous neoplasm, which causes great difficulties in treating this neoplasm in an advanced stage, and the standard approach to this topic does not bring the expected results. There is a need for research on the search for new therapeutic strategies aimed at particular groups of patients. Graphical abstractEffect of three generations of mTOR kinase inhibitors on caspase-3 activity, apoptosis and proliferation in melanoma cell lines.

01 Feb 2023·Advanced biology

CD73/NT5E is a Potential Biomarker for Cancer Prognosis and Immunotherapy for Multiple Types of Cancers

Article

Author: Li, Ping ; Zhu, Jiajia ; Liu, Weishuai ; Wang, Xudong ; Xie, Peng ; Yuan, Yudong ; Shi, Yantao ; Huang, Zhiyong ; Wu, Chao ; Liu, Dongying ; Du, Yuheng ; Li, Huisheng

Abstract:

Cluster of Differentiations 73 (CD73)/ecto‐5'‐nucleotidase (NT5E) is a novel type of immune molecular marker expressed on many tumor cells and involved in regulating the essential immune functions and affecting the prognosis of cancer patients. However, it is not clear how the NT5E is linked to the infiltration levels of the immune cells in pan‐cancer patients and their final prognosis. This study explores the role of NT5E in 33 tumor types using GEPIA, TIMER, Oncomine, BioGPS databases, and several bioinformatic tools. The findings reveal that the NT5E is abnormally expressed in a majority of the types of cancers and can be used for determining the prognosis prediction ability of different cancers. Moreover, NT5E is significantly related to the infiltration status of numerous immune cells, immune‐activated pathways, and immunoregulator expressions. Last, specific inhibitor molecules, like NORNICOTINE, AS‐703026, and FOSTAMATINIB, which inhibit the expression of NT5E in various types of cancers, are screened with the CMap. Thus, it is proposed that NT5E can be utilized as a potential biomarker for predicting the prognosis of cancer patients and determining the infiltration of various immune cells in different types of cancers.

News (Medical) associated with Pimasertib hydrochloride

30 Jul 2024

·www.globenewswire.com

Day One Reports Second Quarter 2024 Financial Results and Corporate Progress

Achieved $8.2 million in OJEMDATM (tovorafenib) net product revenues in initial 2 months of launch Expanded pipeline with DAY301, potential first-in-class Antibody Drug Conjugate (ADC) targeting PTK7 Entered into exclusive licensing agreement with Ipsen to commercialize tovorafenib outside of the U.S. for approximately $111 million upfront in cash and equity investment at a premium Entered into a definitive agreement for an oversubscribed private placement of its securities for total gross proceeds of approximately $175 million Company to host conference call and webcast today, July 30, 8:00 a.m. Eastern Time BRISBANE, Calif., July 30, 2024 (GLOBE NEWSWIRE) -- 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 second quarter 2024 financial results and highlighted recent corporate achievements. “We had an outstanding quarter across all facets of our business,” said Jeremy Bender, Ph.D., chief executive officer of Day One. “Demand for OJEMDA led to strong early launch performance following our first approval, and we made significant progress advancing our programs and pipeline, including the addition of DAY301, a potential first-in-class ADC targeting PTK7 that we expect to be in the clinic in the coming months.” Program Highlights OJEMDA received U.S. Food and Drug Administration (FDA) accelerated approval in April 2024. It is the first and only FDA approved therapy for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. Day One provided updated duration of treatment data from the registrational Phase 2 FIREFLY-1 trial investigating tovorafenib in patients with BRAF-altered, relapsed or progressive pLGG. For the 77 patients enrolled on Arm 1, which was the dataset used to assess OJEMDA’s efficacy, the median duration of treatment is now 23.7 months, with some patients being on treatment out to 32 months. Additional analyses will be presented at future medical conferences. Day One and Ipsen entered into an exclusive licensing agreement to commercialize tovorafenib outside of the U.S. in July 2024. Under the agreement, Day One will receive approximately $111 million upfront in cash and equity investment at a premium with up to approximately $350 million in additional launch and sales milestone payments as well as tiered double-digit royalties starting in mid-teens percentage on net sales. Ipsen secured commercialization rights to tovorafenib outside of the U.S. Day One entered into an exclusive licensing agreement with MabCare Therapeutics for its novel ADC targeting protein-tyrosine kinase 7 (PTK7) in June 2024. The Company expects to dose the first patient in the Phase I portion of the Phase 1/2a clinical trial of DAY301 in the fourth quarter of 2024 or first quarter of 2025.Day One presented a poster on tovorafenib demonstrating reversibility of changes in growth velocity observed in the Phase 2 FIREFLY-1 clinical trial at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. These data were also shared at the 21st International Symposium on Pediatric Neuro-Oncology (ISPNO). Day One made the decision to close the pimasertib program in July 2024, including the FIRELIGHT-1 trial evaluating it in combination with tovorafenib. Resources will be redirected to the DAY301 program and results will be shared at a future medical meeting or publication. The pivotal Phase 3 FIREFLY-2/LOGGIC clinical trial evaluating tovorafenib as a front-line therapy in patients aged 6 months to 25 years with pLGG continues to enroll patients in the United States, Canada, Europe, Australia and Asia, with more than 100 sites activated. Corporate Highlights and Upcoming Milestones Day One announced it entered into a definitive agreement for an oversubscribed private placement of its securities for total gross proceeds of approximately $175.0 million in July 2024. The Company sold the rare pediatric disease Priority Review Voucher awarded by the FDA upon OJEMDA’s approval for total cash proceeds of $108.0 million in May 2024, representing a gain on sale.Commercial operations veteran John Stubenrauch joined Day One in July 2024 as Chief Technology Officer. Dr. Stubenrauch, PhD, MBA, was most recently Chief Operating Officer at Nutcracker Therapeutics and brings more than 25 years of experience developing and commercializing medicines, including ADCs, as well as a broad range of product modalities. Second Quarter 2024 Financial Highlights Cash Position: The Company’s cash, cash equivalents and short-term investments totaled $361.9 million as of June 30, 2024. Product Revenue, Net: OJEMDA net product revenues were $8.2 million for the second quarter of 2024, the first partial quarter of the U.S. launch.R&D Expenses: Research and development expenses were $92.1 million for the second quarter of 2024 compared to $32.2 million for the second quarter of 2023. The increase was primarily due to the MabCare Therapeutics license agreement upfront payment of $55.0 million, increased clinical trial activities related to tovorafenib, and additional employee compensation costs.SG&A Expenses: Selling, general and administrative expenses were $30.2 million for the second quarter of 2024 compared to $17.1 million for the second quarter of 2023. The increase was primarily due to additional employee compensation costs, commercial launch activities, and increased professional service expenses to support company growth.Net Loss: Net loss totaled $4.4 million for the second quarter of 2024 with non-cash stock-based compensation expense of $13.0 million, compared to $45.9 million for the second quarter of 2023 with non-cash stock-based compensation expense of $9.5 million. Upcoming Events 2024 Wedbush PacGrow Healthcare Conference, August 12-14, 2024 Conference Call Day One will host a conference call and webcast today, July 30 at 8:00 a.m. Eastern Time. To access the live conference call by phone, dial 877-704-4453 (domestic) or 201-389-0920 (international), and 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™) and 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 StatementsThis 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 clinical trials, the execution of the Phase 2 and Phase 3 clinical trial for tovorafenib as designed, 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. Day One Biopharmaceuticals, Inc.Condensed Statements of Operations(in thousands, except share and per share amounts)(unaudited) Three Months EndedJune 30, Six Months EndedJune 30, 2024 2023 2024 2023 Revenue: Product revenue, net$8,192 $— $8,192 $— Cost and operating expenses: Cost of product revenue 707 — 707 — Research and development 92,106 32,182 132,316 60,010 Selling, general and administrative 30,186 17,072 56,743 35,099 Total cost and operating expenses 122,999 49,254 189,766 95,109 Loss from operations (114,807) (49,254) (181,574) (95,109)Non-operating income (expense) Gain from sale of priority review voucher 108,000 — 108,000 — Investment income, net 3,962 3,406 8,327 6,872 Other expense, net (10) (15) (20) (19)Total non-operating income, net 111,952 3,391 116,307 6,853 Loss before income taxes (2,855) (45,863) (65,267) (88,256)Income tax expense (1,552) — (1,552) — Net loss$(4,407) $(45,863) $(66,819) $(88,256)Net loss per share, basic and diluted$(0.05) $(0.61) $(0.77) $(1.20)Weighted-average number of common shares used in computing net loss per share, basic and diluted 87,121,310 74,964,878 86,864,545 73,478,567 Day One Biopharmaceuticals, Inc.Selected Condensed Balance Sheet Data(in thousands)(unaudited) June 30,2024 December 31,2023Cash, cash equivalents and short-term investments$361,866 $366,347 Total assets 400,437 376,048 Total liabilities 93,706 29,508 Accumulated deficit (525,404) (458,585)Total stockholders’ equity$306,731 $346,540 DAY ONE MEDIALaura Cooper, Head of Communications media@dayonebio.com DAY ONE INVESTORSLifeSci Advisors, PJ Kelleherpkelleher@lifesciadvisors.com

License out/inClinical ResultDrug ApprovalPhase 1ASCO

20 Jun 2024

·www.pharmamanufacturing.com

Day One inks PTK7-targeting ADC licensing deal with MabCare

Day One Biopharmaceuticals has announced an exclusive licensing agreement with MabCare Therapeutics for MTX-13, a novel antibody-drug conjugate (ADC) targeting protein-tyrosine kinase 7 (PTK7). Under the terms of the agreement, Shanghai-based MabCare will receive $55 million upfront and up to $1.152 billion in additional milestones, along with royalties on net sales outside Greater China. Day One aims to dose the first patient in a phase 1 study by late 2024 or early 2025. The compound, now designated as DAY301, received IND clearance from the FDA in April 2024. It targets PTK7, a transmembrane protein highly expressed in various solid tumors, including esophageal, ovarian, lung, and endometrial cancers in adults, as well as pediatric cancers such as neuroblastoma and osteosarcoma. Preclinical studies have shown that DAY301 has significant antitumor activity, making it a promising candidate for treating both adult and pediatric cancers. Day One Biopharmaceuticals, headquartered in Brisbane, California, focuses on developing targeted cancer therapies. The company’s pipeline includes recently approved tovorafenib (branded Ojemda) and pimasertib, currently in phase 1/2 trials. ADCs work by combining the targeting ability of antibodies with the potent cell-killing power of chemotherapy drugs. This allows for the direct delivery of toxic agents to cancer cells, minimizing damage to healthy cells and potentially reducing side effects compared to traditional chemotherapy. The ADC market is rapidly growing , with several ADCs already approved by regulatory agencies worldwide and many more in clinical development.

License out/inADCDrug Approval

18 Jun 2024

·www.globenewswire.com

Day One Expands Pipeline with Potential First-in-Class Clinical-Stage Antibody Drug Conjugate (ADC) Targeting PTK7 in Solid Tumors for Adult and Pediatric Cancers

Day One receives exclusive license for development and commercialization of MTX-13 (DAY301), which received IND clearance by the FDA in April 2024 Targets PTK7, highly expressed in broad range of adult and pediatric solid tumors BRISBANE, Calif., June 18, 2024 (GLOBE NEWSWIRE) -- Day One Biopharmaceuticals (Nasdaq: DAWN) (“Day One” or the “Company”), a commercial-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, today announced it has entered into an exclusive licensing agreement (the Agreement) with MabCare Therapeutics (MabCare) for MTX-13, a novel ADC targeting protein-tyrosine kinase 7 (PTK7). Pursuant to the terms of the Agreement, Day One has exclusive rights to develop, manufacture, and commercialize MTX-13 worldwide, excluding Greater China. In April 2024, the U.S. Food and Drug Administration (FDA) cleared the investigational new drug (IND) application for MTX-13, which going forward will be identified as DAY301. In pre-clinical studies, DAY301 showed antitumor activity in a wide range of solid tumors. “Our priorities for 2024 are to successfully launch OJEMDA™ (tovorafenib), to advance our existing programs and to expand our pipeline by in-licensing clinical-stage assets that have the potential to transform outcomes for patients of all ages living with cancers,” said Jeremy Bender, Ph.D., chief executive officer of Day One. “We are excited by the opportunity presented by DAY301, and we believe we have the right team in place to develop the program to its full potential.” DAY301 targets PTK7, a highly-conserved, catalytically inactive transmembrane protein that is overexpressed in multiple adult cancers, including esophageal, ovarian, lung, and endometrial cancer, as well as pediatric cancers such as neuroblastoma, rhabdomyosarcoma and osteosarcoma. PTK7 has limited expression in normal tissues or organs, making it an attractive target for therapeutic development. “The addition of DAY301 to our pipeline strategically fits our mission of advancing both pediatric and adult medicines in areas of unmet need with equal urgency,” said Dr. Samuel Blackman, co-founder and head of research and development at Day One. “We believe the linker-payload technology embodied in DAY301 will overcome the limitations of earlier PTK7-targeted ADCs, giving us a potential first-in-class drug against a clinically-validated target. We are excited to add this program to Day One and will look to enter the clinic in the coming months.” Under the terms of the licensing agreement, MabCare will receive $55 million upfront, and is eligible to receive an additional $1.152 billion in development, regulatory and commercial success-based milestones, plus low-to-mid single-digit royalties on net sales outside of Greater China. Day One expects the first patient to be dosed in the Phase I study in the fourth quarter of 2024 or first quarter of 2025. About Day One Biopharmaceuticals Day One Biopharmaceuticals is a commercial-stage biopharmaceutical company that 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™) and pimasertib. Day One is based in Brisbane, California. For more information, please visit www.dayonebio.com or find the Company on LinkedIn or X. Cautionary Note Regarding Forward-Looking StatementsThis 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, including DAY301, expectations regarding planned and current clinical trials and the ability of tovorafenib to treat pLGG or related indications. Statements including words such as “believe,” “plan,” “continue,” “expect,” “will,” “develop,” “signal,” “potential,” or “ongoing” and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Forward-looking statements are subject to risks and uncertainties that may cause Day One’s actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties in this press release and other risks set forth in our filings with the Securities and Exchange Commission, including Day One’s ability to develop, obtain regulatory approval for or commercialize any product candidate, Day One’s ability to protect intellectual property, the potential impact of global business or macroeconomic conditions, including as a result of inflation, 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. DAY ONE MEDIALaura Cooper, Head of Communicationsmedia@dayonebio.com DAY ONE INVESTORSLifeSci Advisors, PJ Kelleherpkelleher@lifesciadvisors.com

License out/inADCPhase 1IND

100 Deals associated with Pimasertib hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14904

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Borderline serous tumour of ovary	Phase 2	US	EMD Serono, Inc.	30 Sep 2013
Borderline serous tumour of ovary	Phase 2	AU	EMD Serono, Inc.	30 Sep 2013
Borderline serous tumour of ovary	Phase 2	BE	EMD Serono, Inc.	30 Sep 2013
Borderline serous tumour of ovary	Phase 2	CA	EMD Serono, Inc.	30 Sep 2013
Borderline serous tumour of ovary	Phase 2	FR	EMD Serono, Inc.	30 Sep 2013
Borderline serous tumour of ovary	Phase 2	PL	EMD Serono, Inc.	30 Sep 2013
Borderline serous tumour of ovary	Phase 2	ES	EMD Serono, Inc.	30 Sep 2013
RAS mutation Cutaneous Melanoma	Phase 2	US	Merck KGaA	05 Dec 2012
RAS mutation Cutaneous Melanoma	Phase 2	AU	Merck KGaA	05 Dec 2012
RAS mutation Cutaneous Melanoma	Phase 2	BE	Merck KGaA	05 Dec 2012

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00982865 (Pubmed \| Target Oncol) Manual	Phase 1	Metastatic melanoma BRAF Mutation \| NRAS Mutation	93	pimasertib (Nine of the 11 responders had tumors with BRAF (n = 6) and/or NRAS (n = 3) mutations.)	priwqqkvul(pdludrgcxy) = utgmpxwkdg nutflbkqqe (jbnybuwlup ) View more	Positive	01 Jan 2021
				pimasertib (ocular melanoma)	xqknkiwovt(gimrkbveos) = qmzlbjzfba uotulsxbpd (qsovvnehhi ) View more
NCT00982865 (Pubmed \| Target Oncol)	Phase 1	Advanced Malignant Solid Neoplasm	180	Pimasertib	qvljfgepvr(yjosyzzmem) = ueoqkwwtsw lrwhrotzyv (houqkskaox ) View more	-	01 Jan 2021
NCT01693068 (Pubmed \| Cancers (Basel)) Manual	Phase 2	RAS mutation Cutaneous Melanoma NRAS Mutation	194	Pimasertib	vzsnmsfmyv(ttxojvkmln) = ywjdrybtvc zzdxltckbo (etfjrlgjip ) View more	Positive	29 Jun 2020
				Dacarbazine	vzsnmsfmyv(ttxojvkmln) = ghemvfjhcc zzdxltckbo (etfjrlgjip ) View more
NCT01936363 (EMR 20006-012, Pubmed) Manual	Phase 2	Ovarian Serous Adenocarcinoma	65	SAR245409+pimasertib	aamrfdyzbb(lfgtgeywxx) = gqngqfdeys aderpwdwrp (mwnjinidvw, 3.5 - 19.7) View more	Negative	01 Feb 2020
				Placebo+pimasertib	aamrfdyzbb(lfgtgeywxx) = hvkliuzlks aderpwdwrp (mwnjinidvw, 5.4 - 22.8) View more
NCT01985191 (Pubmed \| Med J Aust) Manual	Phase 1	Advanced Malignant Solid Neoplasm	26	SAR405838+pimasertib	ipnnvngpod(ncfrbzvrrs) = SAR405838 200 mg QD plus pimasertib 45 mg BID avyrdtefzs (zjfdqguzou ) View more	Positive	01 Feb 2019
NCT01390818 (Pubmed \| Med J Aust) Manual	Phase 1	Advanced Malignant Solid Neoplasm	146	pimasertib+voxtalisib	gzwfmrlriv(kcphuhesuy) = pimasertib 60 mg and voxtalisib 70 mg nbtmlrtnef (hhekaucxbx ) View more	Negative	01 Dec 2018
NCT01016483 (Pubmed \| Int J Cancer) Manual	Phase 1/2	Secondary malignant neoplasm of pancreas First line	141	pimasertib+gemcitabine	wceeirhlkq(eiipcuokqx) = massuhhzga wghurqfvda (cbmwlocnof ) View more	Negative	15 Oct 2018
				gemcitabine+placebo	wceeirhlkq(eiipcuokqx) = enhunwscts wghurqfvda (cbmwlocnof ) View more
NCT01378377 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	33	Pimasertib+Temsirolimus (Pimasertib 45 mg+Temsirolimus 12.5 mg)	piktucvcyy(deniwhzaat) = fiercdieop jovfqidyys (zrzuwhlpaj, keiqmavlbi - ikvevzjeeb) View more	-	30 Jul 2018
				Pimasertib+Temsirolimus (Pimasertib 45 mg+Temsirolimus 25 mg)	piktucvcyy(deniwhzaat) = xvyqexdqxs jovfqidyys (zrzuwhlpaj, tazipebydp - nchszksofy) View more
NCT01693068 (CTgov)	Phase 2	RAS mutation Cutaneous Melanoma	194	Dacarbazine (Dacarbazine)	cszanhawqy(yzugytlryf) = ndnlvqtahn lzbxwbdrda (wjlqmyavfe, hpqwljjlnl - hqkkbepjcb) View more	-	05 Jan 2018
				Pimasertib (Pimasertib)	cszanhawqy(yzugytlryf) = hpirwjfvpt lzbxwbdrda (wjlqmyavfe, sftexhkhue - ejtfidzlso) View more
NCT01378377 (Pubmed \| Invest New Drugs) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	33	pimasertib+temsirolimus	xtgljbemql(pwrldhcclf) = rlaptfvpmf jwvkudjtof (hiaqlmqhrc ) View more	Negative	01 Oct 2017

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