On July 01, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Orion Corporation ("Orion") reported that notice has been provided of the mutual exercise of an option to convert the companies’ ongoing co-development and co-commercialization agreement for opevesostat (MK-5684/ODM-208), an investigational CYP11A1 inhibitor, and other candidates targeting CYP11A1 into an exclusive global license for Merck (Press release, Merck & Co, JUL 1, 2024, View Source [SID1234644624]).

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"We are pleased with the progress made to date in our collaboration with Orion, including the initiation of two pivotal Phase 3 trials evaluating opevesostat in certain patients with metastatic castration-resistant prostate cancer," said Dr. Dean Y. Li, president, Merck Research Laboratories. "We will continue to advance the clinical development program for opevesostat with speed and rigor to help address the needs of patients living with prostate cancer."

"The conversion of this collaboration into a license agreement allows Orion to focus our resources to progress our other promising development candidates while both remaining well positioned to benefit from the development and potential commercialization of opevesostat and meeting our financial objectives," said Liisa Hurme, president and chief executive officer, Orion Corporation. "We believe Merck provides the best choice to maximize the potential of opevesostat, a compound discovered by Orion’s scientists, for the treatment of patients with certain types of prostate cancer."

As previously announced under the companies’ original co-development and co-commercialization agreement, each party was granted an option to convert the co-exclusive license into an exclusive global license for Merck. With the exercise of the option, Merck will gain global exclusive rights to develop and commercialize opevesostat and other candidates targeting CYP11A1 covered by the agreement.

Under the terms of the agreement, Orion is now eligible to receive development milestone payments up to $30 million, regulatory milestone payments up to $625 million and sales-based milestone payments up to $975 million as well as annually tiered royalty payments ranging from a low double-digit rate up to a rate in the low twenties on net sales for any commercialized licensed product. The development and regulatory milestones are determined by the scope of a number of treatment indications and multiple geographies. Annual sales exceeding several billion US dollars would be required to reach the total amount of the sales milestones and higher end of the royalty rate. In addition, as a result of the exercise of the option, Merck will now assume full responsibility for all past and future development and commercialization expenses associated with the candidates covered by the agreement. As a result of the option exercise and Merck’s assumption of expenses, Orion announced it will release €60 million that was reserved in July 2022 to cover Orion’s share of development cost to be accrued from the balance sheet to net sales and operating profit in Q3 2024. Orion will retain responsibility for the manufacture of clinical and commercial supply for Merck. No payment is associated with the exercise of this option.

The exclusive global license is subject to approval under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions, and is expected to become effective in the third quarter of 2024.

About opevesostat and clinical trial program

Opevesostat is an oral, non-steroidal and selective inhibitor of CYP11A1 discovered and developed by Orion and is being investigated for the treatment of hormone-dependent cancers, such as prostate cancer. By inhibiting CYP11A1 activity, opevesostat is designed to suppress the production of all steroid hormones and their precursors that may activate the androgen receptor signaling pathway.

In 2023, Merck and Orion initiated OMAHA1 (NCT06136624) and OMAHA2a (NCT06136650), two pivotal Phase 3 clinical trials evaluating opevesostat in combination with hormone replacement therapy (HRT), for the treatment of certain patients with metastatic castration-resistant prostate cancer (mCRPC).

OMAHA1 is a randomized, open-label Phase 3 trial evaluating opevesostat in combination with HRT for the treatment of patients with later-line mCRPC who have failed one prior new hormonal agent (NHA) and one or two prior taxanes compared to an alternative NHA (abiraterone or enzalutamide). The trial will enroll an estimated 1,200 patients around the world. The primary endpoints are overall survival (OS) and radiographic progression-free survival (rPFS) by androgen receptor ligand-binding domain (AR LBD) mutation status. Secondary endpoints include time to first subsequent therapy (TFST), objective response rate (ORR) and duration of response (DOR).

OMAHA2a is a randomized, open-label Phase 3 trial evaluating opevesostat in combination with HRT for the treatment of patients with front-line mCRPC who have failed one prior NHA compared to physician’s choice of NHA (abiraterone or enzalutamide). The trial will enroll an estimated 1,500 patients around the world. The primary endpoints are OS and rPFS by AR LBD mutation status. Secondary endpoints include TFST, ORR and DOR.

About metastatic castration-resistant prostate cancer

Prostate cancer is the second most common cancer in male patients globally and is associated with a significant mortality rate. Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone. In patients with metastatic castration-resistant prostate cancer (mCRPC), their prostate cancer grows and spreads to other parts of the body, despite the use of androgen-deprivation therapy to block the action of male sex hormones. Approximately 10-20% of patients with prostate cancer are estimated to develop castration-resistant prostate cancer (CRPC) within five years, with at least 84% of these patients presenting with metastases at the time of CRPC diagnosis. Of patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.

On July 01, 2024 Foundation Medicine, Inc. reported that it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOneLiquid CDx to be used as a companion diagnostic for AKEEGA (niraparib and abiraterone acetate) from Janssen Biotech, Inc, a Johnson & Johnson company, the first and only FDA-approved dual-action tablet combining PARP inhibition and hormone therapy for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC) (Press release, Foundation Medicine, JUL 1, 2024, View Source [SID1234644640]). This decision from the FDA follows the approval of FoundationOneCDx, Foundation Medicine’s tissue-based comprehensive genomic profiling (CGP) test, for the same therapy and indication in August 2023.

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Prostate cancer is one of the most common cancers in men.2 BRCA1- or BRCA2-mutated mCRPC is a particularly aggressive form of the disease,3 occurring in approximately 11% of diagnoses.4 Despite progress in developing new treatment options for this condition, BRCA1- or BRCA2-mutated mCRPC remains difficult to treat and patients often face a poor prognosis.5

While some BRCA1 and BRCA2 mutations are germline, somatic mutations are more common.4 While tumor tissue testing is the gold standard for identifying patients with BRCA1 or BRCA2 mutations in prostate cancer, not all patients with mCRPC have sufficient tumor tissue available for testing.6 With this approval, healthcare providers can now leverage a minimally invasive liquid biopsy to identify additional patients with BRCA mutations who may benefit from AKEEGA.

"We know how challenging it can be to obtain a tissue sample for testing in advanced cancers such as mCRPC, making liquid biopsy an incredibly important tool in a provider’s toolbox for the development of personalized treatment plans for their patients," said Mia Levy, M.D., Ph.D., chief medical officer at Foundation Medicine. "The approval of our liquid biopsy test, along with the previous approval for our tissue biopsy test, will enable more patients to access this important therapy option. Additionally, with the ability to leverage a liquid-based test and reflex to a tissue-based test if needed, healthcare providers can feel confident they have accurate genomic information at their fingertips to guide treatment decisions for patients."

From a simple blood sample, FoundationOne Liquid CDx analyzes more than 300 cancer-related genes to provide genomic insights. The test has several companion diagnostic indications across non-small cell lung cancer (NSCLC), prostate cancer, breast cancer, and colorectal cancer, plus a pan tumor indication specific to NTRK1/2/3 fusions.

With today’s approval, Foundation Medicine is the only company that has five FDA-approved companion diagnostic indications for prostate cancer.7 Foundation Medicine is the global leader in companion diagnostic approvals. The company has 60% of all U.S. companion diagnostic approvals for next-generation sequencing (NGS) testing.8

"Men with aggressive prostate cancer need and deserve more options," said Courtney Bugler, President and CEO of ZERO Prostate Cancer. "We applaud Foundation Medicine’s liquid biopsy test because it empowers patients and families with more tools that can potentially help them lead longer, fuller lives."

Foundation Medicine and FoundationOne are registered trademarks of Foundation Medicine, Inc.

On July 1, 2024 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported that the Company has completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for mirdametinib, an investigational MEK inhibitor, for the treatment of pediatric and adult patients with neurofibromatosis type 1- associated plexiform neurofibromas (NF1-PN) (Press release, SpringWorks Therapeutics, JUL 1, 2024, View Source [SID1234644625]).

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"We are pleased to be one step closer towards our goal of bringing mirdametinib to patients with NF1-PN in the U.S. and believe that our ReNeu data support the potential for mirdametinib to be a differentiated and best-in-class therapy for both children and adults living with this devastating disease," said Saqib Islam, Chief Executive Officer of SpringWorks. "We look forward to working closely with the FDA throughout the review process and also plan to file for regulatory approval in the European Union later this year."

The NDA submission includes data from the pivotal Phase 2b ReNeu trial, which evaluated mirdametinib in patients ≥ 2 years of age with NF1-associated PN causing significant morbidity. Results were presented in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and demonstrated that mirdametinib treatment resulted in significant objective response rates confirmed by blinded independent central review, deep and durable responses, improvement in pain and health-related quality of life as well as a manageable safety profile across both the adult and pediatric cohorts.1

The FDA and the European Commission have granted Orphan Drug designation for mirdametinib for the treatment of NF1. The FDA has also granted Fast Track designation for the treatment of patients ≥ 2 years of age with NF1-PN that are progressing or causing significant morbidity and Rare Pediatric Disease designation for the treatment of NF1.

In the second half of 2024, SpringWorks also plans to file a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) for mirdametinib for the treatment of children and adults with NF1-PN.

About the ReNeu Trial

ReNeu (NCT03962543) is an ongoing, multi-center, open-label Phase 2b trial evaluating the efficacy, safety, and tolerability of mirdametinib in patients ≥ 2 years of age with an inoperable NF1-associated PN causing significant morbidity. The study enrolled 114 patients to receive mirdametinib at a dose of 2 mg/m2 twice daily (maximum dose of 4 mg twice daily) without regard to food. Mirdametinib was administered orally in a 3-week on, 1-week off dosing schedule as either a capsule or dispersible tablet. The primary endpoint is confirmed objective response rate defined as ≥ 20% reduction in target tumor volume during the 24 cycle treatment phase, as measured by MRI and assessed by blinded independent central review. Secondary endpoints include safety and tolerability, duration of response, and changes from baseline in patient reported outcomes to Cycle 13. The treatment phase of the trial is complete and results were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Patients who completed the treatment phase were eligible to continue receiving treatment in the optional long-term follow up portion of the study, which is ongoing.

About NF1-PN

Neurofibromatosis type 1 (NF1) is a rare genetic disorder that arises from mutations in the NF1 gene, which encodes for neurofibromin, a key suppressor of the MAPK pathway.2,3 NF1 is the most common form of neurofibromatosis, with an estimated global birth incidence of approximately 1 in 2,500 individuals, and approximately 100,000 patients living with NF1 in the United States.4,5 The clinical course of NF1 is heterogeneous and manifests in a variety of symptoms across numerous organ systems, including abnormal pigmentation, skeletal deformities, tumor growth and neurological complications, such as cognitive impairment.6 Patients with NF1 have an 8 to 15-year mean reduction in their life expectancy compared to the general population.3

NF1 patients have approximately a 30-50% lifetime risk of developing plexiform neurofibromas, or PN, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment; in rare cases, NF1-PN may be fatal.7,8 NF1-PNs are most often diagnosed in the first two decades of life.7 These tumors can be aggressive and are associated with clinically significant morbidities; typically, they grow more rapidly during childhood.9,10

Surgical removal of these tumors is challenging due to the infiltrative tumor growth pattern along nerves and can lead to permanent nerve damage and disfigurement.11 MEK inhibitors have emerged as a validated class of treatment for NF1-PN.12

About Mirdametinib

Mirdametinib is a potent, oral, CNS-penetrant, allosteric small molecule MEK inhibitor in development as a monotherapy treatment for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) and low-grade glioma (LGG), and as a combination therapy for the treatment of several subsets of biomarker-defined metastatic solid tumors. Mirdametinib is an investigational drug for which safety and efficacy have not been established.

Mirdametinib is designed to inhibit MEK1 and MEK2, which occupy pivotal positions in the MAPK pathway. The MAPK pathway is a key signaling network that regulates cell growth and survival and plays a central role in multiple cancers and rare diseases when genetically altered.

The FDA and the European Commission have granted Orphan Drug designation for mirdametinib for the treatment of NF1. The FDA has also granted Fast Track designation for the treatment of patients ≥ 2 years of age with NF1-PN that are progressing or causing significant morbidity and Rare Pediatric Disease designation for the treatment of NF1.

On July 01, 2024 Medincell reported the company will provide an overview of some of its R&D programs related to its cutting-edge Long-Acting Injectable technologies through several presentations and posters at the CRS 2024 conference, from July 8 to 12 in Bologna, Italy, including (Press release, MEDINCELL, JUL 1, 2024, View Source [SID1234644641]):

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Oncology field: Presentation of in vivo data showing the improved immunomodulatory potential of a tumor-targeting monoclonal antibody in melanoma using BEPO technology for peritumoral administration.

Introduction to BEPO STAR: Overview of the novel Medincell’s proprietary Long-Acting Injectable technology designed to enhance controlled delivery across a broader range of drugs and therapeutic areas.

Medincell proprietary in vitro release tool: Presentation of an innovative in vitro lab tool designed to accelerate formulation activities and preclinical candidates selection.

Adolfo Lopez-Noriega, Head of R&D at Medincell, said: "Innovation is our cornerstone, driving our advanced technologies and their groundbreaking applications. Our world-class R&D team is dedicated to continuously pushing the boundaries, enhancing our technology’s reach, and ensuring our position at the forefront of controlled and targeted drug delivery. Our advancements aim to deliver superior therapeutic options through systemic or local delivery in areas where we can make a significant impact, such as psychiatry, oncology, obesity, or pain management. Attending CRS allows us to share our recent achievements and underscores our commitment to forging strong partnerships with both academia and pharmaceutical companies."

Organized by the Controlled Release Society, the CRS Annual Meeting is a prominent conference in the field of controlled release science and technology. It covers a wide range of topics, including drug delivery systems, biomaterials, nanotechnology, polymers, and regulatory aspects of controlled release products. It’s a major event for all academics and pharmaceutical industry professionals involved in the development and application of controlled release technologies.

Event website: View Source

On July 1, 2024 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported that the Company has completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for mirdametinib, an investigational MEK inhibitor, for the treatment of pediatric and adult patients with neurofibromatosis type 1- associated plexiform neurofibromas (NF1-PN) (Press release, SpringWorks Therapeutics, JUL 1, 2024, View Source [SID1234644625]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased to be one step closer towards our goal of bringing mirdametinib to patients with NF1-PN in the U.S. and believe that our ReNeu data support the potential for mirdametinib to be a differentiated and best-in-class therapy for both children and adults living with this devastating disease," said Saqib Islam, Chief Executive Officer of SpringWorks. "We look forward to working closely with the FDA throughout the review process and also plan to file for regulatory approval in the European Union later this year."

The NDA submission includes data from the pivotal Phase 2b ReNeu trial, which evaluated mirdametinib in patients ≥ 2 years of age with NF1-associated PN causing significant morbidity. Results were presented in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and demonstrated that mirdametinib treatment resulted in significant objective response rates confirmed by blinded independent central review, deep and durable responses, improvement in pain and health-related quality of life as well as a manageable safety profile across both the adult and pediatric cohorts.1

The FDA and the European Commission have granted Orphan Drug designation for mirdametinib for the treatment of NF1. The FDA has also granted Fast Track designation for the treatment of patients ≥ 2 years of age with NF1-PN that are progressing or causing significant morbidity and Rare Pediatric Disease designation for the treatment of NF1.

In the second half of 2024, SpringWorks also plans to file a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) for mirdametinib for the treatment of children and adults with NF1-PN.

About the ReNeu Trial

ReNeu (NCT03962543) is an ongoing, multi-center, open-label Phase 2b trial evaluating the efficacy, safety, and tolerability of mirdametinib in patients ≥ 2 years of age with an inoperable NF1-associated PN causing significant morbidity. The study enrolled 114 patients to receive mirdametinib at a dose of 2 mg/m2 twice daily (maximum dose of 4 mg twice daily) without regard to food. Mirdametinib was administered orally in a 3-week on, 1-week off dosing schedule as either a capsule or dispersible tablet. The primary endpoint is confirmed objective response rate defined as ≥ 20% reduction in target tumor volume during the 24 cycle treatment phase, as measured by MRI and assessed by blinded independent central review. Secondary endpoints include safety and tolerability, duration of response, and changes from baseline in patient reported outcomes to Cycle 13. The treatment phase of the trial is complete and results were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Patients who completed the treatment phase were eligible to continue receiving treatment in the optional long-term follow up portion of the study, which is ongoing.

About NF1-PN

Neurofibromatosis type 1 (NF1) is a rare genetic disorder that arises from mutations in the NF1 gene, which encodes for neurofibromin, a key suppressor of the MAPK pathway.2,3 NF1 is the most common form of neurofibromatosis, with an estimated global birth incidence of approximately 1 in 2,500 individuals, and approximately 100,000 patients living with NF1 in the United States.4,5 The clinical course of NF1 is heterogeneous and manifests in a variety of symptoms across numerous organ systems, including abnormal pigmentation, skeletal deformities, tumor growth and neurological complications, such as cognitive impairment.6 Patients with NF1 have an 8 to 15-year mean reduction in their life expectancy compared to the general population.3

NF1 patients have approximately a 30-50% lifetime risk of developing plexiform neurofibromas, or PN, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment; in rare cases, NF1-PN may be fatal.7,8 NF1-PNs are most often diagnosed in the first two decades of life.7 These tumors can be aggressive and are associated with clinically significant morbidities; typically, they grow more rapidly during childhood.9,10

Surgical removal of these tumors is challenging due to the infiltrative tumor growth pattern along nerves and can lead to permanent nerve damage and disfigurement.11 MEK inhibitors have emerged as a validated class of treatment for NF1-PN.12

About Mirdametinib

Mirdametinib is a potent, oral, CNS-penetrant, allosteric small molecule MEK inhibitor in development as a monotherapy treatment for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) and low-grade glioma (LGG), and as a combination therapy for the treatment of several subsets of biomarker-defined metastatic solid tumors. Mirdametinib is an investigational drug for which safety and efficacy have not been established.

Mirdametinib is designed to inhibit MEK1 and MEK2, which occupy pivotal positions in the MAPK pathway. The MAPK pathway is a key signaling network that regulates cell growth and survival and plays a central role in multiple cancers and rare diseases when genetically altered.

The FDA and the European Commission have granted Orphan Drug designation for mirdametinib for the treatment of NF1. The FDA has also granted Fast Track designation for the treatment of patients ≥ 2 years of age with NF1-PN that are progressing or causing significant morbidity and Rare Pediatric Disease designation for the treatment of NF1.