On July 1, 2024 Radionetics Oncology, a biotechnology company discovering and developing novel small molecule G protein coupled receptor (GPCR) targeted radiopharmaceuticals to treat a broad range of solid tumors, reported the formation of a strategic relationship with Eli Lilly and Company to take forward Radionetics’ proprietary GPCR targeting small molecule radiopharmaceuticals (Press release, Radionetics Oncology, JUL 1, 2024, View Source [SID1234644638]).

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Under the terms of the agreement, Radionetics received a $140 million upfront cash payment. As part of the strategic arrangement, Lilly obtained the exclusive right to acquire Radionetics upon conclusion of an exercise period for $1 billion. During the exercise period, Radionetics will continue to build out a proprietary pipeline of therapeutic assets. These will include small molecule radioligand therapeutics targeting GPCRs using the Radionetics proprietary discovery platform and associated intellectual property.

"We are fortunate to have entered into an agreement with Lilly given its global development capability, oncology expertise, and the radiopharmaceutical experience and capabilities Lilly is building following the acquisition of POINT Biopharma," said Paul Grayson, CEO of Radionetics Oncology.

"Furthering our commitment to radiopharmaceutical therapies, this relationship provides access to novel GPCR targets and the discovery capabilities of Radionetics Oncology," said Jacob Van Naarden, Executive Vice President and President, Lilly Oncology.

"Our platform uniquely pairs the power of radiopharmaceuticals with the precision of small molecule targeting to novel GPCRs. We have a specialized team that is focused on rapidly advancing each of our promising programs to bring these much-needed new therapies to patients," said Brett Ewald, Chief Operating Officer.

Cooley LLP is acting as legal advisor to Radionetics. Ropes & Gray LLP is acting as legal advisor to Lilly.

On July 1, 2024 Eisai reported that it has agreed to end its global strategic collaboration with Bristol Myers Squibb for the co-development and co-commercialization of farletuzumab ecteribulin (FZEC), formerly known as MORAb-202, a folate receptor alpha (FRα)-targeting antibody drug conjugate (ADC) due to ongoing portfolio prioritization efforts within Bristol Myers Squibb (Press release, Eisai, JUL 1, 2024, View Source [SID1234644623]). Based on the agreement, Eisai now owns all rights to FZEC and will solely conduct the global development and commercialization of the agent. Eisai will accelerate the development of the agent as a high priority with the hope to deliver it to patients as early as possible. Eisai plans to refund a part of the unused portion of the $200 million payment it received towards research and development expenses from Bristol Myers Squibb under the collaboration agreement and record the remaining as other income.

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FZEC is Eisai’s first ADC and is composed of Eisai’s in-house developed farletuzumab, a humanized IgG1 monoclonal antibody that binds to the FRα, and Eisai’s in-house developed anticancer agent eribulin, using an enzymatically cleavable linker. Currently, three clinical studies are ongoing: Eisai’s Phase 1/2 study for solid tumors (NCT04300556), and Bristol Myers Squibb’s Phase 2 studies for ovarian, peritoneal and fallopian tube cancers (NCT05613088(New Window)) and non-small cell lung cancer (NCT05577715(New Window)).

Eisai positions oncology as a key franchise area and aims to contribute toward the cure of cancers by exploring the depths of human biology. FZEC development for refractory cancers is a testament of our dedication to addressing the unmet medical needs of patients with cancer. Eisai will make continuous efforts to increase the benefits provided to patients with cancer and their families.

[Notes to Editors]

1. Farletuzumab ecteribulin (FZEC, formerly known as MORAb-202)
FZEC is Eisai’s first antibody drug conjugate (ADC) and that is composed of Eisai’s in-house developed farletuzumab, a humanized IgG1 monoclonal antibody that binds to the folate receptor alpha (FRα), and Eisai’s in-house developed anticancer agent eribulin, using an enzymatically cleavable linker. After FZEC enters the target FRα-positive cancer cells, it is thought that the linker is enzymatically cleaved, releasing eribulin from the antibody leading to its antitumor activity. When the anticancer agent and antibody components of an ADC are separated inside a targeted antigen-positive cancer cell, it is theorized that the released anticancer agent also has a bystander effect on neighboring antigen-negative cancer cells and the component cells of the tumor microenvironment. In pre-clinical studies, FZEC demonstrated a bystander effect*, with antitumor activity on the FRα-negative cancer cells surrounding the FRα-positive cancer cells.

The payload eribulin was the first in the halichondrin class of microtubule dynamics inhibitor. Structurally, eribulin is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai, and functions by inhibiting the growth phase of microtubule dynamics which prevents cell division. Eribulin has been approved in countries including Japan, the United States, China, in Europe and in Asia for use in the treatment of advanced breast cancer and liposarcoma (soft tissue sarcoma in Japan).

*Bystander effect: When the anticancer agent and antibody parts of an ADC are separated inside a targeted antigen-positive cancer cell, the released anticancer agent also affects neighboring antigen-negative cancer cells and the component cells of the cancer microenvironment.

On July 01, 2024 KaliVir Immunotherapeutics, Inc., a biotech company developing cutting-edge, multi-mechanistic oncolytic viral immunotherapy programs, reported that the FDA has cleared the Investigational New Drug (IND) application for the STEALTH-001 study of VET3-TGI in patients with incurable, advanced solid tumors (Press release, KaliVir Immunotherapeutics, JUL 1, 2024, View Source [SID1234644639]).

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VET3-TGI is a novel oncolytic immunotherapy which in nonclinical studies specifically targets and preferentially kills tumor cells directly while stimulating anti-cancer immunity by expressing its therapeutic payload consisting of the transgenes for interleukin-12 and a TGFbeta inhibitor. The Phase 1/1b study (ClinicalTrials.gov ID NCT06444815) will evaluate the safety profile and efficacy of VET3-TGI when administered through intravenous infusion or intratumoral injection in patients with advanced, incurable solid tumors. The trial will assess VET3-TGI both as a monotherapy and in combination with checkpoint inhibitor therapy.

"The initiation of this Phase 1/1b clinical study marks a pivotal moment in our continued journey to redefine cancer treatment with oncolytic virus therapy and combat advanced, unresectable or metastatic solid tumors," said Helena Chaye, Ph.D., CEO of KaliVir Immunotherapeutics. "This marks our second initiation of a clinical trial from the VET platform, having announced in 2023 the progress with ASP1012 exclusively licensed to Astellas. We remain fully committed to pushing the boundaries on what is possible with cancer therapies and develop safer, more effective options that have the potential to transform the treatment landscape of oncology."

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.