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On June 18, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved Rozlytrek (entrectinib) for the treatment of adult and paediatric patients with neurotrophic tyrosine receptor kinase (NTRK) fusion-positive, advanced recurrent solid tumours (Press release, Hoffmann-La Roche, JUN 18, 2019, View Source [SID1234537129]). Rozlytrek is the first tumour-agnostic medicine to be approved in Japan that targets NTRK gene fusions, which have been identified in a range of hard-to-treat solid tumour types, including pancreatic, thyroid, salivary gland, breast, colorectal, and lung.1 It has been granted Sakigake designation and orphan drug designation by the MHLW.2

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Rozlytrek is also undergoing regulatory review in Japan for the treatment of people with ROS1 fusion-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).2

"Today’s approval of Rozlytrek represents a new chapter in personalised healthcare, applying advanced diagnostics to deliver precision medicines that target cancers based on their molecular drivers instead of their location in the body," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are proud to be at the forefront of personalised medicine with this novel treatment approach, and we look forward to working with regulatory agencies around the world to bring Rozlytrek to more patients with NTRK fusion-positive cancer, as well as to those with ROS1 fusion-positive NSCLC, as soon as possible."

The data package for this first approval of Rozlytrek includes the pivotal Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials, as well as data from the Phase I/II STARTRK-NG study in paediatric patients. Results showed:

In the pivotal Phase II STARTRK-2 study, Rozlytrek shrank tumours in more than half (objective response rate [ORR] = 56.9 percent) of people with NTRK fusion-positive solid tumours. Objective responses to Rozlytrek were seen across 10 different solid tumour types (median duration of response [DoR] = 10.4 months), including in people with and without CNS metastases at baseline.
Importantly, Rozlytrek also shrank tumours that had spread to the brain in more than half of people (intracranial response [IC] ORR = 50.0 percent).2
In the STARTRK-NG study, Rozlytrek shrank tumours also in children and adolescents who had NTRK fusion-positive solid tumours including the patients with primary CNS tumours.3
The most commonly reported adverse reactions include constipation, altered sense of taste (dysgeusia), diarrhoea, dizziness, fatigue, swelling (oedema), weight increase, anaemia, blood creatinine increase, shortness of breath (dyspnea), and nausea.2
Biomarker testing for NTRK gene fusions is the only way to identify people who may be eligible for treatment with Rozlytrek. Roche is leveraging its expertise in developing personalised medicines and advanced diagnostics, in conjunction with Foundation Medicine, to help identify people with NTRK gene fusions using a companion diagnostic that is undergoing review.

About the supporting data
The data package for this approval includes the pivotal Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials. In addition, data from the Phase I/II STARTRK-NG study in paediatric patients were also included in the submission. The studies enrolled people across 15 countries and more than 150 clinical trial sites. Tumour types evaluated in the studies included breast, cholangiocarcinoma, colorectal, gynaecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.1,2

STARTRK-2 is a Phase II, global, multicentre, open-label basket study in people with solid tumours that harbour an NTRK1/2/3, ROS1 or ALK-positive gene fusion. The primary endpoint is objective response rate (ORR), and duration of response (DoR) is a secondary endpoint. Other secondary outcome measures include time to response, clinical benefit rate, intracranial tumour response, progression-free survival (PFS), central nervous system (CNS) PFS and overall survival (OS).4
STARTRK-1 is a Phase I, multicentre, open-label dose escalation study of a daily continuous dosing schedule in people with solid tumours with NTRK1/2/3, ROS1 or ALK gene fusions in the US and South Korea. The trial assessed the safety and tolerability of Rozlytrek via a standard dose escalation scheme and determined the recommended Phase II dose.5
ALKA-372-001 is Phase I, multicentre, open-label dose escalation study of an intermittent and continuous Rozlytrek dosing schedule in people with advanced or metastatic solid tumours with TRKA/B/C, ROS1 or ALK gene fusions in Italy.2
STARTRK-NG is a Phase I/II dose-escalation and expansion study evaluating the safety and efficacy of Rozlytrek in children and adolescent patients with no curative first-line treatment option, recurrent or refractory extracranial solid tumours or primary CNS tumours, with or without TRK, ROS1 or ALK fusions.3
About NTRK fusion-positive cancer
Neurotrophic tyrosine receptor kinase (NTRK) fusion-positive cancer occurs when the NTRK1/2/3 genes fuse with other genes, resulting in altered TRK proteins (TRKA/TRKB/TRKC) that can activate signaling pathways involved in proliferation of certain types of cancer. NTRK gene fusions are tumour-agnostic, meaning they are present in tumours irrespective of site of origin. These fusions have been identified in a broad range of solid tumour types, including breast, cholangiocarcinoma, colorectal, gynaecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.1

About Rozlytrek
Rozlytrek (RXDX-101) is an oral medicine for the treatment of locally advanced or metastatic solid tumours that harbour NTRK1/2/3, as well as in development for the treatment of ROS1 gene fusions. It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer.6,7 Rozlytrek can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusions.6,7

Rozlytrek has been granted Priority Review by the FDA for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or as an initial therapy when there are no acceptable standard therapies, and for the treatment of people with metastatic, ROS1 fusion-positive NSCLC. It has also been granted Priority Medicines (PRIME) designation by the European Medicines Agency (EMA) and Sakigake designation and orphan drug designation by MHLW.2

On June 17, 2019 Viela Bio reported the successful completion of a $75 million private placement of its Series B preferred stock, bringing the total capital raised since the Company’s launch in February 2018 to more than $300 million (Press release, Viela Bio, JUN 17, 2019, View Source [SID1234539161]). The financing round was led by HBM Healthcare Investments, and additional new investors participating included Viking Global Investors, Cormorant Asset Management, Terra Magnum Capital Partners, Goldman Sachs, and Barer & Son Capital. Existing investors participating included Temasek.

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"We are pleased that our ongoing development of our clinical programs continues to attract capital from leading healthcare investors. This financing will support our upcoming regulatory milestone—the anticipated filing of our Biologics License Application with the U.S. FDA for our lead product candidate, inebilizumab, for the treatment of neuromyelitis optica spectrum disorder, or NMOSD," said Bing Yao, Ph.D. Executive Chairman and Chief Executive Officer. "NMOSD is a severe, debilitating, and sometimes fatal neurological disease for which there is currently no approved treatment. While our priority is to serve this patient population through the successful approval and launch of inebilizumab, we believe this financing also puts us in a strong position to pursue additional new indications with inebilizumab. Furthermore, we believe this financing will allow us to advance the entirety of our clinical pipeline, which is comprised of several additional clinical candidates for a range of rare autoimmune and inflammatory diseases."

On June 17, 2019 2019 BioNTech SE, a biotechnology company focused on the clinical development of patient-specific immunotherapy for the treatment of cancer and other serious diseases, reported the launch of DuoBody PD-L1x4-1BB product candidate clinical development (Press release, BioNTech, JUN 17, 2019, View Source [SID1234539089]). PD-L1x4-1BB is a bi-specific antibody developed in collaboration with Genmab A / S. The Phase I / IIa trial will test the bi-specific antibody in patients with metastatic or surgically non-removable solid tumors that can not be treated with standard care. The DuoBody PD-L1x4-1BB is the first co-developed product candidate to reach the clinical phase. The costs and profits of the partnership are shared 50 to 50 times.

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"The launch of the Phase I / IIa clinical trial with a product candidate that was developed in just four years confirms our highly productive partnership with Genmab," said Prof. Dr. med. Ugur Sahin, CEO of BioNTech . "The dual-immunostimulatory mechanism of action of the DuoBody PD-L1x4-1BB can address a variety of cancers, as well as providing an additional level of treatment options in our cancer therapy portfolio. We also strengthen BioNTech’s strategy of using new targets and mechanisms to unlock the full potential of the immune system for cancer immunotherapy. "

The DuoBody PD-L1x4-1BB is a novel bi-specific antibody that combines the checkpoint blockade of the inhibitory PD-1: PD-L1 signaling axis with the conditional stimulation of T cells by activating the 4-1BB receptor and thereby increase the proliferation of activated T cells for the efficient control of cancer cells. The original idea and the concept of combining the two mechanisms are based on scientific studies conducted by BioNTech. The unblinded study with the DuoBody PD-L1x4-1BB (ClinicalTrials.gov Identification Number NCT03917381) is carried out at several sites and consists of two parts: a dose-escalation study (Phase I, First-in-Human) and a dose-expansion study (Phase IIa). Primary endpoints include, above all, safety assessment, including the review of dose-limiting toxicity and adverse events.

On June 17, 2019 CASI Pharmaceuticals, Inc. (Nasdaq: CASI), a U.S. biopharmaceutical company that is focusing on developing and accelerating the launch of innovative therapeutics and pharmaceutical products in China, the U.S., and throughout the world, reported the signing of a license agreement for exclusive worldwide license and commercialization rights to an autologous anti-CD19 T-cell therapy product (CNCT19) from Juventas Cell Therapy Ltd., a China-based domestic company located in Tianjin City, China (Press release, CASI Pharmaceuticals, JUN 17, 2019, View Source [SID1234537128]). Juventas will continue to develop CNCT19 with CASI’s participation on the program’s steering committee. CASI will be responsible for payment of certain future development milestones and sales royalties.

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In connection with the license, CASI Pharmaceuticals (Wuxi) Co., Ltd., a joint venture in which CASI owns 80% of the registered capital, will invest RMB 80 million (approximately 11.6 million) in Juventas through a wholly owned Chinese subsidiary in lieu of the upfront payment for the license.

CNCT19 targets CD19, a B-cell surface protein widely expressed during all phases of B-cell development and a validated target for B-cell driven hematological malignancies. CD19-targeted CAR constructs from several different institutions have demonstrated consistently high antitumor efficacy in children and adults with relapsed B-cell acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL), and B-cell non-Hodgkin lymphoma (B-NHL). CD19 antigen is the most frequently used biomarker in the CAR-T cell therapy clinical trials for hematological malignant diseases such as leukemia and lymphoma. Juventas has previously submitted two INDs to the NMPA for Acute Lymphoblastic Leukemia (ALL) and Non-Hodgkin Lymphoma (NHL) indications; approvals of which are expected in late 2019.

Larry Zhang, President of CASI (Beijing) Pharmaceuticals Co., Ltd., a wholly owned subsidiary of CASI, commented, "We are extremely excited by this partnership and are encouraged by the preliminary data which showed promising results that may offer the potential to be the best in class anti-CD19 CAR-T product for Non-Hodgkin lymphoma (NHL) and B-cell acute lymphoblastic leukemia (B-ALL). We are excited about our role to help drive innovation in this exciting therapeutic area and remain committed to providing a range of solutions to patients with hematological malignancies. We look forward to working with Juventas to advance the clinical development of this therapy and for CASI to begin commercial planning."

Alexander Zukiwski, M.D., CASI’s Chief Medical Officer commented, "Juventas has made significant strides thus far with regulatory filings in two treatment areas, B-cell acute lymphoblastic leukemia (B-ALL) and Non-Hodgkin lymphoma (NHL), and have identified sites for both Phase 1 and Phase 2 studies in China. We look forward to reviewing the data from the Phase 1 and 2 studies once they are available."