Chugai to In-license ROS1/TRK Inhibitor Entrectinib

On July 17, 2018 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has entered into a license agreement with F. Hoffmann-La Roche, Ltd. for the ROS1/TRK inhibitor entrectinib (Development Code: RG6268), which is under development for tumors that harbor ROS1 or NTRK fusions (Press release, Chugai, JUL 17, 2018, View Source [SID1234529698]).

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Under the terms of agreement, Chugai obtains exclusive rights for the development and marketing of entrectinib in Japan, and will make upfront and milestone payments to Roche.

Entrectinib is an orally bioavailable CNS-active tyrosine kinase inhibitor that potently and selectively inhibits the ROS1 (c-ros oncogene 1) and TRK (tropomyosin receptor kinase) family. Entrectinib targets ROS1 fusion gene positive non-small cell lung cancer and NTRK fusion gene positive solid tumors. Currently, Roche is conducting a global phase II clinical study (The STARTRK-2 study). Entrectinib has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) in May 2017 and PRIME (PRIority MEdicines) Designation by the European Medicines Agency (EMA) in October 2017 for the treatment of NTRK fusion positive solid tumors. In Japan, entrectinib also received the Sakigake Designation by the Ministry of Health, Labour and Welfare in March 2018.

To date, Chugai has made contributions to healthcare through the launches of innovative anti-cancer agents. With the addition of the ROS1/TRK inhibitor entrectinib to our product portfolio, Chugai’s strength as a leading pharmaceutical company in the area of oncology will be enriched, enabling Chugai to make greater contributions to the advancement of cancer treatment.

Chugai is committed to continuing its efforts to meet unmet medical needs by effectively utilizing the research and development resources of Roche to find innovative new drugs.

About ROS1 fusion gene positive non-small cell lung cancer
ROS1 fusion gene is an abnormal gene that can be formed by fusing the ROS1 gene and other genes (CD74, etc.) as a result of chromosomal translocation for some reason. The ROS1 fusion kinase made from ROS1 fusion gene is thought to promote cancer cell proliferation. ROS1 fusion gene is found in about one to two percent of non-small cell lung cancer, among which it is more expressed in adenocarcinoma.

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 translocation. 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 appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, gastrointestinal stromal tumor (GIST), infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas.

About Sakigake Designation
Sakigake aims at shortening pre-market review period for innovative medical products that satisfy certain criteria by designating such products during the early stages of development, and providing prioritized consultation services and substantial pre-application consultation. By taking advantage of the benefits offered by Sakigake, the target review period for the designated products will be reduced to as short as 6 months.

Inflection Biosciences Announces Publication of Positive Data for Dual Mechanism Inhibitor Against Chronic Lymphocytic Leukaemia

On July 17, 2018 Inflection Biosciences Ltd, a private company developing innovative therapeutics for cancer, reported the publication of preclinical data showing the company’s dual mechanism PIM/PI3 kinase inhibitor IBL-202 has promise as a treatment for chronic lymphocytic leukaemia (CLL) (Press release, Inflection Biosciences, JUL 17, 2018, View Source [SID1234527747]). This research has been published in the most recent issue of the peer-reviewed British Journal of Haematology.

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The preclinical research was conducted in collaboration with Dr. Oliver Giles Best of the Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, Australia, and a member of the CLL Australian Research Consortium (CLLARC), Sydney, Australia.

Despite significant advances in treatment, CLL remains an incurable disease. Given the growing body of evidence suggesting CLL cells may adapt to, survive and even proliferate under hypoxic conditions of the tumour microenvironment, new treatment options which are effective under these conditions are required.

These published results show that IBL‐202 is cytotoxic against CLL cells under in vitro conditions that mimic the hypoxic tumour microenvironment. The publication also demonstrates the significant effects of IBL‐202 on CD49d and CXCR4 gene expression and on the migration, cycling and proliferation of CLL cells, suggesting the drug may significantly impair the migratory and proliferative capacity of the leukaemic cells.

Dr. Best, lead author on the publication, commented: "Collectively, this data demonstrates that dual inhibition of the PIM and PI3 kinases by IBL‐202 may be an effective strategy for targeting CLL cells, particularly within the environmental niches known to confer drug‐resistance."

The complete article titled ‘The dual inhibitor of the phosphoinositol‐3 and PIM kinases, IBL‐202, is effective against chronic lymphocytic leukaemia cells under conditions that mimic the hypoxic tumour microenvironment’ can be accessed here.

July 2018 Investor Presentation.

On July 17, 2018 Advaxis presented the corporate presentation (Presentation, Advaxis, JUL 17, 2018, View Source [SID1234527762]).

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Johnson & Johnson Reports 2018 Second-Quarter Results

On July 17, 2018 Johnson & Johnson (NYSE: JNJ) reported sales of $20.8 billion for the second quarter of 2018, an increase of 10.6% as compared to the second quarter of 2017 (Press release, Johnson & Johnson, JUL 17, 2018, View Source [SID1234527728]).

Operational sales results increased 8.7% and the positive impact of currency was 1.9%. Domestic sales increased 9.4%. International sales increased 11.8%, reflecting operational growth of 7.9% and a positive currency impact of 3.9%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 6.3%, domestic sales increased 5.7% and international sales increased 6.8%.*

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Net earnings and diluted earnings per share for the second quarter of 2018 were $4.0 billion and $1.45, respectively. Second-quarter 2018 net earnings included after-tax intangible amortization expense of approximately $1.0 billion and a charge for after-tax special items of approximately $0.8 billion. Second-quarter 2017 net earnings included after-tax intangible amortization expense of approximately $0.4 billion and a charge for after-tax special items of approximately $0.8 billion. Excluding after-tax intangible amortization expense and special items, adjusted net earnings for the current quarter were $5.7 billion and adjusted diluted earnings per share were $2.10, representing increases of 14.0% and 14.8%, respectively, as compared to the same period in 2017.* On an operational basis, adjusted diluted earnings per share also increased 11.5%.* A reconciliation of non-GAAP financial measures is included as an accompanying schedule.

"Our strong second-quarter results reflect double-digit growth in our Pharmaceutical business and the accelerating sales momentum in our Medical Devices business, driven by the continued growth of our market leading products and strategic new launches. We remain focused on investing in innovation and meeting the needs of our customers by delivering innovative products and solutions that position the company to deliver long-term, sustainable growth," said Alex Gorsky, Chairman and Chief Executive Officer. "Our talented J&J colleagues are united in our efforts to address some of the most critical health and consumer needs of people around the world.
The Company updated its sales guidance for the full-year 2018 to a range of $80.5 to $81.3 billion. This reflects an increase in expected operational growth to a range of 4.5% to 5.5%, partially offset by the estimated lower favorable impact of currency. Additionally, the Company updated its adjusted earnings guidance for full-year 2018 to a range of $8.07 to $8.17 per share. This reflects an increase in expected operational growth to a range of 8.5% to 9.9%, partially offset by the estimated lower favorable impact of currency.

Segment Sales Performance
Worldwide Consumer sales of $3.5 billion for the second quarter 2018 represented an increase of 0.7% versus the prior year, consisting of an operational decrease of 0.4% and a positive impact from currency of 1.1%. Domestic sales decreased 0.7%, international sales increased 1.9%, which reflected no change in operational sales and a positive currency impact of 1.9%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 0.9%, domestic sales decreased 0.7% and international sales increased 2.1%*.
Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by over-the-counter products including TYLENOL analgesics and digestive health products, international beauty products primarily NEUTROGENA, OGX and Dr. Ci Labo, partially offset by lower sales of baby care products. During the quarter, the divestiture of the anti‐dandruff shampoo brand NIZORAL and certain other ketoconazole‐based shampoo brands was completed.

Worldwide Pharmaceutical sales of $10.4 billion for the second quarter 2018 represented an increase of 19.9% versus the prior year with an operational increase of 17.6% and a positive impact from currency of 2.3%. Domestic sales increased 17.7%; international sales increased 22.9%, which reflected an operational increase of 17.5% and a positive currency impact of 5.4%. Sales included the impact of Actelion Ltd which contributed 6.6%, to worldwide operational sales growth. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 11.0%, domestic sales increased 10.2% and international sales increased 11.9%.*
Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by STELARA (ustekinumab), a biologic for the treatment of a number of immune-mediated inflammatory diseases, ZYTIGA (abiraterone acetate), an oral, once-daily medication for use in combination with prednisone for the treatment of metastatic, castration-resistant prostate cancer, DARZALEX (daratumumab), for the treatment of patients with multiple myeloma, IMBRUVICA (ibrutinib), an oral, once-daily therapy approved for use in treating certain B-cell malignancies, a type of blood or lymph node cancer, TREMFYA (guselkumab), for the treatment of adults living with moderate to severe plaque psoriasis. SIMPONI/SIMPONI ARIA (golimumab), a biologic for the treatment of a number of immune-mediated inflammatory diseases, INVEGA SUSTENNA/XEPLION/TRINZA/TREVICTA (paliperidone palmitate), long-acting, injectable atypical antipsychotics for the treatment of schizophrenia in adults, and XARELTO (rivaroxaban), an oral anticoagulant.

During the quarter, the U.S. Food and Drug Administration (FDA) approved an additional indication for DARZALEX (daratumumab) in combination with VELCADE (bortezomib), a proteasome inhibitor; melphalan, an alkylating agent; and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. The European Commission granted marketing authorization for JULUCA (dolutegravir/rilpivirine), a two-drug regimen, once-daily, single-pill for the treatment of HIV-1. A supplemental New Drug Application was submitted to the FDA seeking to expand the indication of OPSUMIT (macitentan) to include the treatment of adults with inoperable chronic thromboembolic pulmonary hypertension (CTEPH, WHO Group 4) to improve exercise capacity and pulmonary vascular resistance.
Also in the quarter, the acquisition of BeneVir Biopharm, Inc., a privately-held, biopharmaceutical company specializing in the development of oncolytic immunotherapies, was completed. In addition, a worldwide collaboration

was entered into with Bristol-Myers Squibb Company to develop and commercialize Factor XIa inhibitors, including BMS-986177, for the prevention and treatment of major thrombotic conditions.
Worldwide Medical Devices sales of $7.0 billion for the second quarter 2018 represented an increase of 3.7% versus the prior year consisting of an operational increase of 1.9% and a positive currency impact of 1.8%. Domestic sales increased 1.1%; international sales increased 6.0%, which reflected an operational increase of 2.5% and a positive currency impact of 3.5%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 2.9%, domestic sales increased 1.7% and international sales increased 4.1%.*
Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by ACUVUE contact lenses and surgical products in the Vision business; electrophysiology products in the Interventional Solutions business; biosurgicals and international endocutters in the Advanced Surgery business; wound closure products in the General Surgery business and trauma products in the Orthopaedics business, partially offset by declines in the Diabetes Care business and spine products in the Orthopaedics business.
During the quarter, the Company announced acceptance of the binding offer from Platinum Equity to acquire its LifeScan business for approximately $2.1 billion, subject to customary adjustments. The Company also announced receipt of a binding offer from Fortive Corporation to acquire its Advanced Sterilization Products business for an aggregate value of approximately $2.8 billion, subject to customary adjustments. In addition, the FDA approved iDESIGN Refractive Studio, part of a next generation LASIK platform that measures the eye inside and out to enable highly precise personalized vision correction.
In July, the acquisition of assets from Medical Enterprises Distribution, LLC, a privately held developer of surgical impactor technology, including the automated ME1000 Surgical Impactor for use in hip replacement, was completed.

OncoSec Presents Update from Triple Negative Breast Cancer Program at 3rd Global Insight Conference on Breast Cancer

On July 17, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ: ONCS), a company developing intratumoral cancer immunotherapies, reported that Sharron Gargosky, PhD, Chief Clinical and Regulatory Officer, presented a clinical update of the Company’s intratumoral therapy, ImmunoPulse tavokinogene telseplasmid (TAVO), as well as an overview of the ongoing and anticipated clinical programs involving TAVO in triple-negative breast cancer (TNBC) (Press release, OncoSec Medical, JUL 17, 2018, https://ir.oncosec.com/news/detail/1950/oncosec-presents-update-from-triple-negative-breast-cancer-program-at-3rd-global-insight-conference-on-breast-cancer [SID1234527738]). The presentation, titled "Intra-tumoral delivery of tavokinogene telseplasmid (pIL-12) by electroporation: immunomodulation in melanoma and triple negative breast cancer," took place at the 3rd Global Insight Conference on Breast Cancer in Valencia, Spain.

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"We were grateful for the opportunity to present at the 3rd Global Insight Conference on Breast Cancer and share progress from our TAVO clinical programs with the clinicians, biotechnology executives, and industry opinion leaders in attendance. Metastatic TNBC is a heterogeneous cancer with a poor prognosis where less than five percent of pre-treated patients achieve an objective response to PD-1/PD-L1 checkpoint treatments," said Dr. Gargosky. "The marked synergy shown in these patients strongly suggest that IL-12 may have primed the tumor microenvironment, impacting the clinical result. The combination of TAVO and checkpoint inhibition represents a highly promising new therapeutic approach for TNBC and warrants a formal evaluation given the extremely low response rate in women who have failed multiple prior therapies."

The ongoing Phase 1 TNBC study, OMS-140 (NCT02531425), is designed to determine whether TAVO as a single cycle of monotherapy can elicit a pro-inflammatory molecular and histological signature in treated as well untreated tumors. The study has reached its target enrollment of 10 patients. Several of these patients were subsequently treated with an anti-PD-1 checkpoint inhibitor treatment(s) as their next therapy. As previously reported at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, immunological signals were observed on an individual patient basis, and clinically meaningful objective tumor responses have been observed in both TAVO treated and untreated lesions following the anti-PD-1 checkpoint inhibitor treatment. A detailed case study of one such patient, along with information regarding clinical observations and safety data, were presented at this conference.

Following these observations, the Company entered a clinical collaboration with Merck to evaluate the combination of TAVO with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in a Phase 2 clinical trial, KEYNOTE-890 (NCT03567720). KEYNOTE-890 is a study of TAVO in combination with KEYTRUDA in TNBC patients with inoperable locally advanced or metastatic TNBC who have progressed on more than one line of prior therapy. Patients will be treated with the combination of TAVO with pembrolizumab. The proposed primary endpoint is to assess efficacy as measured by objective response rate (ORR) by independent central review (ICR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. KEYNOTE-890 is expected to initiate in the third quarter of 2018.