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Home Roche and Blueprint Medicines Enter $1.7B Collaboration for Pralsetinib, with CStone Holding Greater China Rights

Roche and Blueprint Medicines Enter $1.7B Collaboration for Pralsetinib, with CStone Holding Greater China Rights

Jul 14, 2020 21:18 CST Updated 21:18
Roche

Oncology Drug Research, Development, and Manufacturing

Blueprint Medicines

Anticancer Drug Developer


July 14, 2020 /BioValleyBIOON/ -- Roche recently signed a licensing and collaboration agreement with Blueprint Medicines, the partner of CStone Pharmaceuticals, securing exclusive rights to co-develop and commercialize the oral RET inhibitor pralsetinib in regions outside the United States (excluding Greater China). In the United States, Genentech, a member of the Roche Group, obtained joint commercialization rights for pralsetinib and will share profits equally. This transformative partnership creates a pathway for Blueprint to achieve financial self-sustainability.

In June 2018, CStone Pharmaceuticals obtained from Blueprint Medicines the exclusive rights to develop and commercialize three drugs (pralsetinib, avapritinib, and fisogatinib) in Greater China (Mainland China, Hong Kong, Macao, and Taiwan). On the 9th of this month, CStone Pharmaceuticals announced that the registrational study of pralsetinib in Chinese patients with RET fusion-positive non-small cell lung cancer (NSCLC) had achieved the expected results, and plans to submit a new drug application to the National Medical Products Administration (NMPA) in the near future.

Pralsetinib, designed by Blueprint Medicines, is an oral, potent, and highly selective inhibitor of RET fusions and mutations (including predicted resistance-conferring mutations), indicated for the treatment of RET-altered non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other types of thyroid cancer, as well as other solid tumors. Furthermore, pralsetinib has demonstrated potential as a tumor-agnostic therapy. Roche and Blueprint also plan to expand the development of pralsetinib across various treatment settings and explore the development of next-generation RET inhibitors within the framework of their collaboration.

The total value of this agreement amounts to $1.7 billion. Under the terms of the agreement, Blueprint will receive an upfront cash payment of $675 million and a $100 million equity investment in Blueprint common stock from Roche. In addition, Blueprint is eligible to receive up to $927 million in contingent development, regulatory, and sales milestone payments, as well as royalties based on net product sales outside the United States. Roche and Blueprint will share global research and development costs according to pre-specified cost-sharing ratios and will equally share profits and losses in the United States.

RET-activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and MTC, yet selective therapeutic options targeting these genetic alterations remain very limited. Amid the growing demand for more targeted therapies with the potential to deliver clinical benefits to patients with these cancers, this collaboration reflects Roche’s strategy to provide treatments specifically tailored to individual patientsTumorfeature-based therapies, and provide truly personalized medical services.

In lung cancer, pralsetinib will complement Roche’s already approved broad portfolio of medicines, including Alecensa, Rozlytrek, Tecentriq, Avastin, and Tarceva, and will further support Roche’s strategic focus on understanding driver mutations in lung cancer through personalized treatment approaches. Beyond lung cancer, the “tumor-agnostic” potential of pralsetinib is expected to further expand Roche’s ongoing commitment to discovering new ways to treat cancer based on the genetic mutations of the disease, regardless ofTumorin vivo origin site.

Roche PharmaceuticalsJames Sabry, Head of Collaboration, stated: “We are delighted to enter into this collaboration with Blueprint Medicines, a partner we have worked with for four years. Our goal is to provide a potentially transformative treatment option as soon as possible for cancer patients harboring rare RET alterations. In delivering pralsetinib to patients, we will leverage ourTumorour global influence and expertise in the field of medicine, as well as ourDiagnosisand capabilities in leveraging real-world data, to achieve the goal of providing personalized treatment for patients.”

Molecular Structure of Pralsetinib (Image Source: medchemexpress.com)

The Rearranged during Transfection (RET) gene is a proto-oncogene that undergoes rearrangement during transfection, from which it derives its name. This gene encodes RET, a receptor tyrosine kinase located on the cell membrane, and its abnormalities serve as rare drivers in various types of tumors. Activating RET fusions and mutations are key disease drivers in many cancer types, including non-small cell lung cancer (NSCLC) and medullary thyroid carcinoma (MTC). RET fusions are involved in approximately 1–2% of NSCLC patients and about 10–20% of patients with papillary thyroid carcinoma (PTC), while RET mutations are implicated in approximately 90% of patients with advanced MTC. Furthermore, low-frequency RET alterations have been observed in colorectal cancer, breast cancer, pancreatic cancer, and other malignancies, and RET fusions have also been detected in EGFR-mutant NSCLC patients who have developed drug resistance.

Pralsetinib is an oral (once-daily), potent and highly selective investigational drug targeting oncogenic RET variants, being developed for the treatment of RET-altered NSCLC, MTC, and other types of thyroid cancer, as well as other solid tumors. Previously, in the United StatesFDAPralsetinib has been granted Breakthrough Therapy Designation (BTD) for the treatment of RET fusion-positive non-small cell lung cancer (NSCLC) that has progressed following platinum-based chemotherapy, and for patients with RET-mutant positive medullary thyroid cancer (MTC) who require systemic therapy and have no alternative treatment options.

Blueprint Medicines has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for pralsetinib for the treatment of RET fusion-positive non-small cell lung cancer (NSCLC). The FDA has granted priority review to this NDA, with an expected decision date of November 23, 2020. Additionally, Blueprint Medicines has submitted NDAs to the U.S. FDA for the treatment of RET mutation-positive medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer.FDAMTC application accepted and will be processed in real timeTumorReview of the ROTR Pilot Project.

Pralsetinib was designed by the research team at Blueprint Medicines based on its proprietary compound library. In preclinical studies, pralsetinib consistently demonstrated subnanomolar potency against the most common RET gene fusions, activating mutations, and predicted resistance mutations. Notably, pralsetinib exhibited an 80-fold higher selectivity for RET compared to VEGFR2. Furthermore, pralsetinib showed significantly improved RET selectivity relative to approved multi-kinase inhibitors. By inhibiting both primary and secondary mutations, pralsetinib holds promise for overcoming and preventing the development of clinical resistance. This therapy is expected to achieve durable clinical responses in patients harboring various RET alterations, with a favorable safety profile.

Notably, Eli Lilly’s Retevmo (selpercatinib) is the first approved RET inhibitor. The drug was developed byEli LillyDeveloped by its oncology subsidiary, Loxo Oncology, and approved in the United States this MayFDAApproved for the treatment of three types of RET gene alterations (mutations or fusions)TumorPatients: Non-small cell lung cancer (NSCLC), medullary thyroid carcinoma (MTC), other types of thyroid cancer.

Retevmo is the first therapy approved specifically for patients with cancers harboring RET gene alterations. Specifically, the drug is approved for the treatment of: (1) adult patients with advanced or metastatic NSCLC; (2) patients aged ≥12 years with advanced or metastatic MTC requiring systemic therapy; and (3) patients aged ≥12 years with advanced RET fusion-positive thyroid cancer requiring systemic therapy who have become refractory to radioactive iodine treatment or are not eligible for such treatment. Notably, up to 50% of patients with RET fusion-positive NSCLC may haveTumorBrain Metastases: In patients with baseline brain metastases, Retevmo demonstrated robust efficacy, with an intracranial objective response rate (CNS-ORR) of up to 91% (n=10/11).

Retevmo is a selective RET kinase inhibitor that blocks RET kinase and prevents cancer cell growth. The drug may also affect healthy cells, leading to side effects. Therefore, prior to initiating Retevmo therapy, patients must be confirmed through laboratory testingTumorRET gene alterations are present. (Bioon.com) (Bioon.com)