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 DiseaseUrogenital Diseases

Active Indication

Ovarian Cancer

Inactive Indication

Acute Myeloid LeukemiaAdvanced Hepatocellular CarcinomaAdvanced Malignant Solid Neoplasm+ [19]

Originator Organization

Santhera Pharmaceuticals (USA), Inc.

Active Organization

Santhera Pharmaceuticals (USA), Inc.

Inactive Organization

Merck KGaA

EMD Serono, Inc.Day One Biopharmaceuticals, Inc.

+ [1]

License Organization

Day One Biopharmaceuticals, Inc.Merck KGaA

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (United States)

Structure/Sequence

Molecular FormulaC15H16ClFIN3O3

InChIKeyHIEXZUXKTABHCP-PPHPATTJSA-N

CAS Registry1236361-78-6

Clinical Trials associated with Pimasertib hydrochloride

NCT04789668

/ TerminatedPhase 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

NCT01992874

/ CompletedPhase 1

A Multi-Center, Open-Label, Single 60 mg Dose, Two Period, Two Sequence Cross-Over Trial to Investigate the Relative Bioavailability of Two Solid Oral Pimasertib Formulations in Cancer Patients

This is a Phase 1, multi-center, open-label, single-dose, 2 period, 2 sequence cross-over trial to investigate the relative bioavailability of 2 solid oral pimasertib formulations in cancer subjects (Part A), followed by open-label pimasertib administration (Part B and trial extension phase).

Start Date30 Nov 2013

Sponsor / Collaborator

EMD Serono, Inc.

NCT01985191

/ CompletedPhase 1

A Phase 1 Study of Combination Therapy With SAR405838 and Pimasertib in Patients With Advanced Cancer

Primary Objectives:
To determine the recommended Phase 2 dose of SAR405838 / pimasertib combination therapy in patients with solid tumors.
To assess the anti-tumor activities of SAR405838 / pimasertib in patients with solid tumors.
Secondary Objectives:
To characterize the pharmacokinetic profile of SAR405838 and pimasertib.
To evaluate the pharmacodynamic effect of the SAR405838 and pimasertib.
To characterize genetic status in tumor tissue and circulating tumor DNA.

Start Date01 Nov 2013

Sponsor / Collaborator

Sanofi

[+1]

100 Clinical Results associated with Pimasertib hydrochloride

100 Translational Medicine associated with Pimasertib hydrochloride

100 Patents (Medical) associated with Pimasertib hydrochloride

113

Literatures (Medical) associated with Pimasertib hydrochloride

01 Jul 2025·CHEMISTRY & BIODIVERSITY

Integrated Computational and Experimental Insights Into MEK1/2 Inhibitors: Structural Validation, Docking, ADMET, Molecular Dynamics, and Anticancer Evaluation

Article

Author: Teli, Ghanshyam ; Matada, Gurubasavaraja Swamy Purawarga ; Pal, Rohit

ABSTRACT:

This study explores the therapeutic potential of novel MEK1/2 inhibitors targeting the MAPK pathway, emphasizing their critical role in cancer progression. An integrated computational approach, including molecular docking, pharmacophore modeling, molecular dynamics simulations, and DFT analysis, was employed to evaluate the binding affinity, stability, and pharmacological properties of FDA‐approved and experimental compounds. Structural validation of MEK1 (PDB ID: 1S9J) and MEK2 (PDB ID: 1S9I) revealed z‐scores of −6.89 and −7.13, respectively, with 90.6% and 86.7% of residues in the most favored regions, confirming the reliability of the protein models. Docking studies identified RO5126766 as a lead compound, exhibiting binding energies of −10.1 kcal/mol with MEK1 and −9.5 kcal/mol with MEK2. Molecular dynamics simulations further demonstrated the stability of the RO5126766–MEK1 and RO5126766–MEK2 complexes, with RMSD values ranging from 0.95 to 4.22 Å. The in vitro anticancer assays highlighted the exceptional potency of RO5126766, with IC50 values of 12.87 ± 98.36 nM against MCF‐7 (hormone receptor‐positive breast cancer), 15.08 ± 94.36 nM against MDA‐MB‐231 (triple‐negative breast cancer), and 60.89 ± 70.58 nM against A549 (lung cancer). ADMET analysis confirmed high gastrointestinal absorption, favorable drug‐likeness, and lack of blood‐brain barrier permeability. In addition, DFT studies indicated an optimal HOMO–LUMO energy gap (0.15816 eV), chemical hardness (0.16189 eV), and strong molecular interactions corroborated by MEP analysis. Collectively, these findings establish RO5126766 as a potent and selective MEK1/2 inhibitor, demonstrating significant potential as a targeted therapeutic agent for aggressive and treatment‐resistant cancers.

14 Apr 2025·Journal of Chemical Information and Modeling

Identification and Experimental Validation of NETosis-Mediated Abdominal Aortic Aneurysm Gene Signature Using Multi-omics, Machine Learning, and Mendelian Randomization

Article

Author: Wu, Chengsong ; Kan, Shangguang ; Ren, Yuanyuan ; Zhang, Pan ; Cui, Yue ; Zhang, Chan ; Xiong, Yuyan ; Zhang, Xuejiao ; Li, Yang ; Zhang, Liyao

Abdominal aortic aneurysm (AAA) is a life-threatening disorder with limited therapeutic options. Neutrophil extracellular traps (NETs) are formed by a process known as "NETosis" that has been implicated in AAA pathogenesis, yet the roles and prognostic significance of NET-related genes in AAA remain poorly understood. This study aimed to identify key AAA- and NET-related genes (AAA-NETs-RGs), elucidate their potential mechanisms in contributing to AAA, and explore potential therapeutic compounds for AAA therapy. Through bioinformatics analysis of multiomics and machine learning, we identified six AAA-NETs-RGs: DUSP26, FCN1, MTHFD2, GPRC5C, SEMA4A, and CCR7, which exhibited strong diagnostic potential for predicting AAA progression, were significantly enriched in pathways related to cytokine-cytokine receptor interaction and chemokine signaling. Immune infiltration analysis revealed a causal association between AAA-NETs-RGs and immune cell infiltration. Cell-cell communication analysis indicated that AAA-NETs-RGs predominantly function in smooth muscle cells, B cells, T cells, and NK cells, primarily through cytokine and chemokine signaling. Gene profiling revealed that CCR7 and MTHFD2 exhibited the most significant upregulation in AAA patients compared to non-AAA controls, as well as in in vitro AAA models. Notably, genetic depletion of CCR7 and MTHFD2 strongly inhibited Ang II-induced phenotypic switching, functional impairment, and senescence in vascular smooth muscle cells (VSMCs). Based on AAA-NETs-RGs, molecular docking analysis combined with the Connectivity Map (CMap) database identified mirdametinib as a potential therapeutic agent for AAA. Mirdametinib effectively alleviated Ang II-induced phenotypic switching, biological dysfunction, and senescence. These findings provide valuable insights into understanding the pathophysiology of AAA and highlight promising therapeutic strategies targeting AAA-NETs-RGs.

01 Apr 2025·Cancer research communications

Preclinical Activity of the Type II RAF Inhibitor Tovorafenib in Tumor Models Harboring Either a BRAF Fusion or an NF1 Loss-of-Function Mutation

Article

Author: Venetsanakos, Eleni ; Perino, Samantha ; Wang, Yujin ; Lal-Nag, Madhu ; Rastogi, Shubhra ; Blackman, Samuel C.

Abstract:

Genomic alterations and dysregulation of the MAPK pathway have been described in many different types of cancers. BRAFV600 mutations and BRAF fusions, found in both pediatric and adult cancers, are oncogenic drivers that drive constitutive activation of the RAF pathway. Neurofibromin 1 (NF1) loss-of-function (LOF) mutations, which occur in many cancer types, result in decreased neurofibromin GAP function, thus activating RAS. Tovorafenib is an oral selective, central nervous system–penetrant, type II RAF inhibitor which inhibits RAF monomers and dimers. In this study, the impact of tovorafenib alone or in combination with MEK inhibitor, pimasertib, was explored in adult or pediatric tumor models harboring BRAF fusions or NF1-LOF mutations. Tovorafenib resulted in tumor regression in an AGK::BRAF fusion melanoma patient-derived xenograft model in vivo, while exhibiting little antitumor activity in NF1-LOF tumor models. In vitro anti-proliferative activity of tovorafenib and pathway modulation was evaluated in NF1-LOF tumor cell lines. Little anti-proliferative activity was observed in the NF1-LOF tumor cell lines treated with tovorafenib. In NF1-LOF tumor cells treated with tovorafenib, an increase in phosphorylated ERK was observed at low concentrations, with inhibition of phosphorylated ERK at higher concentrations. When tovorafenib was combined with pimasertib in vitro, synergy was observed in an NF1-LOF embryonal rhabdomyosarcoma patient-derived xenograft model ex vivo and an NF1-LOF Malignant peripheral nerve sheath tumors (MPNST) cell line in vitro, suggesting that vertical pathway inhibition is needed in the NF1-LOF mutant setting.

Significance::

Tovorafenib demonstrated efficacy in BRAF fusion but not in NF1-LOF mutant tumor models. Vertical pathway inhibition by combining type II RAF plus MEK inhibitors may have clinical relevance in NF1-LOF mutant tumors.

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
D10426	-	-	DB14904

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Borderline epithelial tumor of ovary	Phase 2	United States	EMD Serono, Inc.	30 Sep 2013
Borderline epithelial tumor of ovary	Phase 2	Australia	EMD Serono, Inc.	30 Sep 2013
Borderline epithelial tumor of ovary	Phase 2	Belgium	EMD Serono, Inc.	30 Sep 2013
Borderline epithelial tumor of ovary	Phase 2	Canada	EMD Serono, Inc.	30 Sep 2013
Borderline epithelial tumor of ovary	Phase 2	France	EMD Serono, Inc.	30 Sep 2013
Borderline epithelial tumor of ovary	Phase 2	Poland	EMD Serono, Inc.	30 Sep 2013
Borderline epithelial tumor of ovary	Phase 2	Spain	EMD Serono, Inc.	30 Sep 2013
Borderline serous tumour of ovary	Phase 2	United States	EMD Serono, Inc.	30 Sep 2013
Borderline serous tumour of ovary	Phase 2	Australia	EMD Serono, Inc.	30 Sep 2013
Borderline serous tumour of ovary	Phase 2	Belgium	EMD Serono, Inc.	30 Sep 2013

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04789668 (CTgov)	Phase 1/2	Melanoma, Cutaneous Malignant \| Metastatic Solid Tumor \| Hematologic Neoplasms ... View more	8	Pimasertib+Bintrafusp Alfa (Dose-Level)	rtetprdaap = onlfhdmrvr czpyodfwyn (oymaytoaul, emexicwohm - sldddszpaa) View more	-	18 Mar 2026
				Pimasertib+Bintrafusp (Dose-Level 1)	gprbvvtdab(zqqiwpvpxf) = djkmimnmsn stkweicvpz (tfwgnclmbr, chpmxlagpl - akpubonlul) View more
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.)	nnhhgfjcjx(yghvmimezu) = zgkelhdjox pfjndwqtmj (sywzpvsnsk ) View more	Positive	01 Jan 2021
				pimasertib (ocular melanoma)	piqzcswvfy(pmnvlzdtwb) = cheyrubtxb fuikouezqv (cikgfbydjb ) View more
NCT00982865 (Pubmed \| Target Oncol)	Phase 1	Advanced Malignant Solid Neoplasm	180	Pimasertib	nvvytngpty(xrmmnvzwjn) = yblrzmluhi tpqmqgjtki (bzhynbdqqj ) View more	-	01 Jan 2021
NCT01693068 (Pubmed \| Cancers (Basel)) Manual	Phase 2	RAS mutation Cutaneous Melanoma NRAS Mutation	194	Pimasertib	woocfyatjr(kcblubhene) = xcdwdhmovj csrdwkeewf (fwfzrnochp ) View more	Positive	29 Jun 2020
				Dacarbazine	woocfyatjr(kcblubhene) = hbcpwrflof csrdwkeewf (fwfzrnochp ) View more
NCT01936363 (EMR 20006-012, Pubmed) Manual	Phase 2	Ovarian Serous Adenocarcinoma	65	SAR245409+pimasertib	smbuekxbcl(rglyvhrudc) = hgadxwnjxs fluvogsfxi (nckocwrfca, 3.5 - 19.7) View more	Negative	01 Feb 2020
				Placebo+pimasertib	smbuekxbcl(rglyvhrudc) = nulbdxmidu fluvogsfxi (nckocwrfca, 5.4 - 22.8) View more
NCT01985191 (Pubmed \| Med J Aust \| Br J Cancer) Manual	Phase 1	Advanced Malignant Solid Neoplasm	26	SAR405838+pimasertib	bxgjgwedpg(ditbinutkn) = SAR405838 200 mg QD plus pimasertib 45 mg BID voldixepjm (shldrryqoo ) View more	Positive	01 Feb 2019
NCT01390818 (Pubmed \| Med J Aust) Manual	Phase 1	Advanced Malignant Solid Neoplasm	146	pimasertib+voxtalisib	hihtcolmdj(uoohhxbllv) = pimasertib 60 mg and voxtalisib 70 mg nbpgaiecpw (dpjefyjdbc ) View more	Negative	01 Dec 2018
NCT01016483 (Pubmed \| Int J Cancer) Manual	Phase 1/2	Metastatic Pancreatic Cancer First line	141	pimasertib+gemcitabine	auhryxujtu(jkksciizts) = bjlbjqqonn lcxhhnfxux (mxtkkovspp ) View more	Negative	15 Oct 2018
				gemcitabine+placebo	auhryxujtu(jkksciizts) = yfjfvoblha lcxhhnfxux (mxtkkovspp ) View more
NCT01378377 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	33	Pimasertib+Temsirolimus (Pimasertib 45 mg+Temsirolimus 12.5 mg)	tlhpgwmmms = lahegduayn idqskuoiub (jwrjmhsrki, twbokgbmfk - tiyyexleiu) View more	-	30 Jul 2018
				Pimasertib+Temsirolimus (Pimasertib 45 mg+Temsirolimus 25 mg)	tlhpgwmmms = qplqukoqsa idqskuoiub (jwrjmhsrki, fpbxlhsfmc - wlondaxple) View more
NCT01693068 (CTgov)	Phase 2	RAS mutation Cutaneous Melanoma	194	Dacarbazine (Dacarbazine)	vdtwclawoc(lwtucqzdvc) = muxqemiypk chzdvczejf (jhokglveig, ftblvbzxhu - qdyeycvuuq) View more	-	05 Jan 2018
				Pimasertib (Pimasertib)	vdtwclawoc(lwtucqzdvc) = kjsemgqmpd chzdvczejf (jhokglveig, syoeuyoxlh - mmfewkiybk) View more

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