On June 27, 2019 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that the Ministry of Health Labour and Welfare (MHLW) granted an additional approval for FoundationOne CDx Cancer Genomic Profile as a companion diagnostic for Rozlytrek (entrectinib) for the treatment of neurotrophic tyrosine receptor kinase (NTRK) fusion positive solid tumors on June 26, 2019 (Press release, Chugai, JUN 27, 2019, View Source [SID1234537292]). The approval enables FoundationOne CDx Cancer Genomic Profile to be used as a companion diagnostic for Rozlytrek by detecting NTRK fusion genes (fusion genes between NTRK1, NTRK2, NTRK3 and other genes). Rozlytrek is a ROS1/TRK inhibitor and was approved for the treatment of adult and pediatric patients with NTRK fusion positive advanced and recurrent solid tumors on June 18, 2019.

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"The conventional concept of cancer treatment focuses on the site where the cancer started. However, it is drastically changing with the emergence of a completely new approach called tumor agnostic treatment; an approach which targets genomic mutations that drive cancers instead of the tumor location in the body. We are proud of the MHLW approval of FoundationOne CDx Cancer Genomic Profile as a companion diagnostic for Rozlytrek which represents this new tumor agnostic treatment approach," said Dr. Minoru Watanabe, Chugai’s Vice President, Head of Foundation Medicine Unit. "A comprehensive genomic profiling test is especially beneficial in identifying rare gene mutations expressed in multiple cancer types, including NTRK gene fusions. Chugai will further strive to provide services to help physicians’ swift and appropriate decision making in order to realize patient-centric healthcare."

Developed by Foundation Medicine Inc., FoundationOne CDx Cancer Genomic Profile is a next-generation sequencing based in vitro diagnostic device for the detection and analysis of substitutions, insertion and deletion alterations, and copy number alterations in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from patient’s tumor tissues. As a comprehensive companion diagnostic function, it can be also used as a companion diagnostic for certain molecular-targeted drugs approved in Japan.

As a leading company in the field of oncology, Chugai is committed to realize advanced personalized oncology care and contribute to patients and healthcare providers through comprehensive genomic profiling.

[Note]
A press release issued on June 18, 2019: Anti-Cancer Agent Rozlytrek, Approved for the Treatment of NTRK Fusion Gene Positive Advanced/Recurrent Solid Tumors
View Source

Approval information The underlined part has been newly added.

Brand name FoundationOne CDx Cancer Genomic Profile
Nonproprietary name
Gene mutation analysis program (for use in cancer genome profiling)
Somatic gene mutation analysis program (for use in assessing anticancer drug indications)
Intended uses or indications
The Product is used for comprehensive genomic profiling of tumor tissues in patients with solid cancers.
The Product is used for detecting gene mutations and other alterations to support the assessment of drug indications listed in the table below.
Alterations Cancer type Relevant drugs
EGFR exon 19 deletions and EGFR exon 21 L858R alterations Non-small cell lung cancer (NSCLC) afatinib dimaleate, erlotinib hydrochloride, gefitinib, osimertinib mesylate
EGFR exon 20 T790M alterations osimertinib mesylate
ALK fusion genes alectinib hydrochloride, crizotinib, ceritinib
BRAF V600E and V600K alterations Malignant melanoma dabrafenib mesylate, trametinib dimethyl sulfoxide, vemurafenib
ERBB2 copy number alterations (HER2 gene amplification positive) Breast cancer trastuzumab (genetical recombination)
KRAS/NRAS wild-type Colorectal cancer cetuximab (genetical recombination), panitumumab (genetical recombination)
NTRK1/2/3 fusion gene Solid tumors entrectinib
Conditions for approval
The necessary measures must be taken to ensure that the product is used by a physician with adequate knowledge and experience of cancer genomic medicine at a medical institution with a cancer genome profiling-based medical system pursuant to the "Guidelines for the Development of Core Hospitals and Other Facilities for Cancer Genomic Medicine," and in compliance with the scope and timing of testing stipulated in the most recent guidelines, etc., of relevant academic societies.
Appropriate procedures and controls to protect personal information and up-to-date security and privacy protection measures to prevent unauthorized access must be implemented for tumor tissue specimens sent to the laboratory and for information obtained from these specimens.
Quality control of input data must be performed as described in the Remarks column of the attached Application Form. Any changes to the quality control of input data as described in the Remarks column of the Application Form (excluding minor changes specified by Order of the MHLW in Article 23-2-5, paragraph (11) of the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices ["the Act"]) must be approved by the MHLW Minister pursuant to Article 23-2-5, paragraph (11) of the Act. Note that this approval applies mutatis mutandis to the provisions of Article 23-2-5 paragraph (13), Article 23-2-6, and Article 23-2-7 of the Act.
About Rozlytrek
Rozlytrek is an oral tyrosine kinase inhibitor that blocks ROS1 (c-ros oncogene 1) and TRK (neurotrophin receptors) family strongly and selectively. It blocks ROS1 and TRK kinase activity, and inhibits proliferation of cancer cells with ROS1 or NTRK gene fusions. Rozlytrek has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration and Priority Medicines designation by the European Medicines Agency for the treatment of NTRK fusion gene positive, locally advanced or metastatic solid tumors in adult and pediatric patients who have either progressed following prior therapies or have no acceptable standard therapies. FDA has granted priority review for Rozlytrek for the treatment of NTRK fusion-positive solid tumors and ROS1 fusion-positive non-small cell lung cancer (NSCLC). In Japan, Chugai filed an application for approval of ROS1 fusion gene positive NSCLC in March 2019.

About NTRK fusion gene positive cancer
NTRK fusion gene is an abnormal gene that can be formed by fusing the NTRK genes (NTRK1, NTRK2, NTRK3 encode TRKA, TRKB, TRKC protein, respectively) and other genes (ETV6, LMNA, TPM3, etc.) as a result of chromosomal translocation1-3). The TRK fusion kinase made from NTRK fusion gene is thought to promote cancer cell proliferation. There is very rare expression of NTRK fusion but in various adult and pediatric solid tumors, including infantile fibrosarcoma, glioma, glioblastoma, diffuse intrinsic pontine glioma (DIPG), congenital mesoblastic nephroma, melanoma, inflammatory myofibroblastic tumor (IMT), uterus sarcoma, soft tissue tumor, gastrointestinal stromal tumor (GIST), secretory carcinoma of breast, secretory carcinoma of salivary gland, cancer of unknown primary, lung cancer, colorectal cancer, appendiceal cancer, breast cancer, gastric cancer, ovarian cancer, thyroid cancer, cholangiocarcinoma, pancreatic cancer, head and neck cancer, and various sarcomas.

Trademarks used or mentioned in this release are protected by laws.

[References]

Martin-Zanca D, Hughes SH, Barbacid M. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature 1986; 319(6056): 743-8.
Martin-Zanca D, Oskam R, Mitra G, Copeland T, Barbacid M. Molecular and iochemical Characterization of the Human trk Proto-Oncogene. Molecular and Cellular Biology 1989; 9(1): 24-33.
Lange AM, Lo HW. Inhibiting TRK Proteins in Clinical Cancer Therapy. Cancers 2018; 10: 105.

On June 27, 2019 Innovent Biologics, Inc. (Innovent) (HKEX: 01801) and Eli Lilly and Company ("Lilly") jointly reported that the National Medical Products Administration (NMPA) has accepted its new drug application (NDA) for IBI301, a co-developed biosimilar product candidate of rituximab (MabThera/Rituxan) (Press release, Innovent Biologics, JUN 27, 2019, View Source [SID1234537283]). This NDA by Innovent is the fourth that has been accepted by the NMPA following Tyvyt (sintilimab injection), IBI303 (a biosimilar product candidate of adalimumab injection, granted priority review status) and IBI305 (a biosimilar product candidate of bevacizumab injection, granted priority review status).

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IBI301 is a recombinant human-mouse chimeric anti-cell surface protein (anti-CD20) monoclonal antibody for injection co-developed by Lilly and Innovent for the treatment of non-Hodgkin’s lymphoma (NHL) and other diseases. Rituximab was first approved by the U.S. Food and Drug Administration (FDA) for the treatment of NHL in November 1997, followed by approvals in chronic lymphocytic leukemia (CCL), rheumatoid arthritis (RA), and other disease indications. Branded rituximab has been well-recognized for its proven efficacy and safety profile. Despite the high unmet demand for effective cancer therapies in China, the adoption rate of rituximab is relatively low due to low affordability. The biosimilar product candidate of rituximab, IBI301, is expected to offer a high-quality and affordable alternative to patients in China.

The NDA is based on clinical data generated from two clinical studies, namely: a Phase 3 comparative study of efficacy and safety in patients with diffuse large B-cell lymphoma (DLBCL) and a pharmacokinetic (PK) study in patients with CD20-positive B-cell lymphoma. Both studies directly compare IBI301 to rituximab and have met their pre-defined primary endpoints.

"Two clinical studies have been conducted with rituximab injection as the control arm. Based on the high-quality clinical data, the NDA of IBI301 has been accepted by NMPA. We believe that the high-quality rituximab biosimilar will improve drug availability and benefit more patients and their families," said Professor Lugui Qiu from Blood Diseases Hospital, Chinese Academy of Medical Sciences.

"The Phase 3 study comparing IBI301 with rituximab when each is used in combination with standard chemotherapy (CHOP) in patients with DLBCL shows an objective response rate (ORR) and safety profile consistent with that of branded rituximab, which suggests biosimilarity between IBI301 and rituximab injection. We hope that the drug can be launched soon to benefit more lymphoma patients," said Professor Jun Zhu, Beijing Cancer Hospital.

Dr. Li Wang, Senior Vice-President of Lilly China and Head of Lilly China Drug Development and Medical Affairs, commented, "The NDA of IBI301 represents another millstone of strategic cooperation between Lilly and Innovent. We hope that IBI301 can be approved soon in order to offer an affordable treatment option for lymphoma patients in China."

"At present, we have fourteen assets in clinical research stage, four products in phase 3 clinical trials, and one, Tyvyt (sintilimab injection), is now successful approved and launched on the market. IBI301 is the fourth NDA filing Innovent has submitted to NMPA. We are excited about reaching this important milestone and hope to bring the high-quality drug to more patients. We’ll strive to deliver high-quality biopharmaceutical drugs from our rich pipeline to benefit more and more ordinary people," said Dr. Hui Zhou, Vice President and Head of Oncology Strategy and Medical Sciences of Innovent.

About non-Hodgkin’s lymphoma

Malignant lymphoma is one of the most common hematological malignancies in China. It is one of the top ten malignant tumors with high morbidity and mortality. In recent years, the incidence of malignant lymphoma has been rising. According to histopathology, lymphoma can be divided into Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL), of which NHL accounts for the majority. NHL is a general term for a series of related but different lymphoid malignant tumors. Most (80-85%) originates from B cells. The rest originates from T cells or an undetermined cell type. More than 95% of B-cell non-Hodgkin’s lymphoma cells express CD20. The incidence of NHL increases with age. The most common type of NHL in China is diffuse large B-cell lymphoma (DLBCL), accounting for 40-50% (about 30-40% in Western countries). DLBCL is a moderately malignant to highly malignant invasive lymphoma that progresses rapidly and leads to the death of patients within a few months without treatment. The clinical efficacy and safety of rituximab in CD20-positive non-Hodgkin’s lymphoma have been confirmed in several large-scale clinical trials.

About IBI301

IBI301 is a biosimilar of rituximab, a recombinant human-mouse chimeric anti-CD20 monoclonal antibody for injection co-developed by the Group and Eli Lilly and Company. Rituximab is a monoclonal antibody which binds to CD20 antigen on the surface of B lymphocytes and mediates complement-dependent cytotoxicity ("CDC") and antibody-dependent cellular cytotoxicity ("ADCC"). The normal and malignant B cells in the mediator dissolve, thereby achieving an anti-tumor therapeutic effect.

On June 27, 2019 Bracco Imaging S.p.A., a global leader in diagnostic imaging, reported that it had signed a definitive agreement to acquire Blue Earth Diagnostics, a molecular imaging company based in Oxford, UK (Press release, Bracco, JUN 27, 2019, View Source [SID1234537282]). Subject to customary closing conditions, completion of the transaction is expected in Q3 of this calendar year.

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Bracco Imaging will acquire all outstanding shares of privately-held Blue Earth Diagnostics for the equity value of $ 450 million, plus closing adjustment estimated at $25 million, from leading healthcare company Syncona and Blue Earth Diagnostics’ management team. Upon closing of the transaction, Blue Earth Diagnostics will be a subsidiary of Bracco Imaging, led by its current leadership team and will retain the well-established Blue Earth Diagnostics name. Blue Earth Diagnostics employs approximately 100 people and is expected to generate revenues of $ 140M in the year to September 2019, primarily in the US.

The first novel PET molecular imaging agent developed by Blue Earth Diagnostics is Axumin (F18-fluciclovine) injection approved in the United States (US) and the European Union for PET imaging in men with suspected recurrent prostate cancer based on elevated prostate specific antigen (PSA) levels following prior treatment. The company’s pipeline includes innovative Prostate Specific Membrane Antigen (PSMA)-targeted radiohybrid ("rh") agents, which are a clinical-stage, investigational class of theranostic compounds, with potential applications in both the imaging and treatment of prostate cancer.[1]

Prostate cancer is the most common cancer in men, with an estimated number of more than 170 thousand new cases in 2019 in the US.[2] While most cases of primary prostate cancer can be treated successfully, the cancer will recur in up to one third of cases and in a third of those recurrences, patients develop distant metastases leading to a fatal outcome[3]. In two separate studies which evaluated the utility of Axumin (F18-fluciclovine) PET/CT in providing physicians with actionable information for the management of men with recurrent prostate cancer, the intended management plan was changed for approximately 60% of the study subjects, based on the results of the Axumin PET/CT scan.[4]

F18-fluciclovine has a broad range of other potential applications in cancer imaging and Blue Earth Diagnostics is investigating the molecule for other cancers including in neuro-oncology.

"Blue Earth Diagnostics’ innovative products and pipeline will significantly enhance Bracco Imaging’s portfolio in precision medicine and personalized diagnostics, while expanding our range of nuclear oncology imaging solutions in the Urology segment and other specialties," said Fulvio Renoldi Bracco, Chief Executive Officer, Bracco Imaging. "We are thrilled to welcome to Bracco this world class team with exceptional product development and commercialization expertise."

"The acquisition of Blue Earth Diagnostics by Bracco Imaging is a validation of the proven success of Axumin in prostate cancer, its potential uses beyond prostate cancer, and the PSMA pipeline under development," said Dr. Jonathan Allis, D.Phil., Chief Executive Officer, Blue Earth Diagnostics. "Bracco Imaging’s global footprint and clinical research and marketing support will enable us to further leverage our high-value platform for innovative radiopharmaceuticals to inform clinical management and guide care for cancer patients around the world."

J.P. Morgan is acting as Exclusive Financial Adviser to Bracco and as sole Underwriter of the financing for its [$450 million] acquisition of Blue Earth Diagnostics Ltd from Syncona Ltd. Santa Maria Law Firm and Greenberg Traurig acted as legal advisors.

On June 26, 2019 BridgeBio Pharma, Inc. ("BridgeBio") reported the pricing of its initial public offering of 20,500,000 shares of its common stock at a price to the public of $17.00 per share, above the range of $14.00 to $16.00 (Press release, BridgeBio, JUN 26, 2019, View Source [SID1234576265]). In addition, BridgeBio has granted the underwriters a 30-day option to purchase up to 3,075,000 additional shares of its common stock. The shares are expected to begin trading on the Nasdaq Global Select Market on June 27, 2019, under the ticker symbol "BBIO" and the offering is expected to close on July 1, 2019, subject to customary closing conditions.

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J.P. Morgan Securities LLC, Goldman Sachs & Co. LLC, Jefferies LLC, SVB Leerink LLC, KKR Capital Markets LLC, Piper Jaffray & Co., Mizuho Securities USA LLC, BMO Capital Markets Corp. and Raymond James & Associates, Inc. are acting as book-running managers for the offering.

A registration statement relating to the securities being sold in this offering has been filed with and was declared effective by the U.S. Securities and Exchange Commission on June 26, 2019. This offering is being made only by means of a written prospectus. Copies of the final prospectus may be obtained, when available, from the office of J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, telephone: 1-866-803-9204 or by emailing [email protected]; Goldman, Sachs & Co., Attention: Prospectus Department, 200 West Street, New York, NY 10282, telephone: 1-866-471-2526 or by emailing [email protected]; Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, telephone: 1-877-547-6340, or by emailing [email protected]; or SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, Massachusetts 01220, telephone: 1-800-808-7525, ext. 6132, or by emailing [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On June 26, 2019 Vaccibody AS reported strong immunogenicity data from the neoantigen cancer vaccine clinical trial VB N-01 (Press release, Vaccibody, JUN 26, 2019, View Source [SID1234537300]). Immunogenicity was assessed in two patients with renal cell carcinoma (RCC) and two patients with squamous cell carcinoma of the head and neck (SCCHN) after treatment with a VB10.NEO in combination with checkpoint inhibitor therapy as per protocol. Before VB10.NEO vaccination, these patients had been treated with the checkpoint inhibitor nivolumab for 12-32 months with stable disease as best response. One patient was progressing at start of vaccination. All patients had low tumour mutational burden ranging from 1.7-3.2 mutations/Mb. The top 20 neoepitopes predicted by Vaccibody’s proprietary NeoSELECTTM algorithm was selected for each of the fully personalized VB10.NEO neoantigen vaccines. Immunogenicity to each individual neoepitope has so far been assessed after 3 to 6 vaccinations of VB10.NEO by an in vitro stimulated IFN-γ ELISpot. Strong T cell responses were observed in all these first four patients tested. T cell responses were significantly increased in post-vaccination samples towards 63% of the neoepitopes. The response to the vaccine was very solid with an average increase of more than 1200 SFU per million PBMC which is on average a 250-fold increase from baseline. The breadth and the strength increased with number of vaccinations. An amplification of existing neoepitope-specific T cells as well as de novo responses were observed in all patients.

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Agnete Fredriksen President and CSO of Vaccibody, commented: We are very pleased to see the strong T cell responses observed in all of the first four patients at the initial assessments. We are excited to see that the vaccine was able to induce so strong T cell responses even in the patients with a history of many lines of previous treatment and no objective response to long-term treatment with anti-PD-1. All these first patients had low tumour mutational burden (TMB) leaving the number of mutations limited for selection of immunogenic neoepitopes, hence we believe the high percentage of the neoantigen-specific immune responses observed substantiates Vaccibody’s unique neoepitope prediction method and delivery mechanism. We are very intrigued by the de novo responses induced by the vaccine. The baseline responses and hence the number of de novo responses were surprisingly different between the patients assessed so far and we are looking forward to characterizing the T cells in more detail and follow the clinical responses in these patients