On February 21, 2020 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has obtained approval for its anti-cancer agent/ALK inhibitor, Alecensa capsule 150 mg (nonproprietary name: alectinib hydrochloride) from the Ministry of Health, Labour and Welfare for an additional indication of recurrent or refractory ALK fusion gene-positive anaplastic large-cell lymphoma (Press release, Chugai, FEB 21, 2020, View Source [SID1234554594]).

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"Chemotherapy is usually used for the treatment of ALCL. However, standard therapies have not been established in patients with post-chemotherapy recurrent ALCL, resulting in a growing demand for new pharmaceutical products," said Dr. Osamu Okuda, Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit. "The approval for the additional indication of Alecensa will offer a new treatment option to patients with these unmet medical needs. We will strive to make Alecensa as one of the standard therapies for ALK-positive non-small cell lung cancer, with the aim of making a significant contribution to the treatment of hematologic cancers."

This approval is based on the results from the investigator initiated study (the ALC-ALCL study) started in May 2015. The study was conducted as a part of the "Research Project on Practical Application of Innovative Cancer Therapy" by Japan Agency for Medical Research and Development. In the ALC-ALCL study, the response rate (primary endpoint, assessed by the central review committee) and safety were evaluated in 10 patients with relapsed or refractory ALK-positive ALCL who are 6 years or older (6-70 years). The response rate which was the primary endpoint was 80.0% (two-sided 90% confidence interval: 56.15-95.91%). The incidence of adverse reactions was 100.0%. The most common adverse reactions were maculopapular rash (40.0 %, 4/10 cases), upper respiratory tract infection, bronchitis and increased blood alkaline phosphatase (30.0 %, 3/10 cases), respectively.

[Reference information]
Media release issued by Chugai on June 3, 2019
Title: Chugai Files for Additional Indication of ALK Inhibitor ALECENSA for Recurrent or Refractory ALK Fusion Gene-Positive Anaplastic Large Cell Lymphoma (ALCL)
View Source

About ALK-positive anaplastic large-cell lymphoma (ALCL)
ALCL is non-Hodgkin’s lymphoma originated in T-cells in lymphocytes, which is one of four subtypes of peripheral T-cell lymphoma classified as malignant lymphoma. The malignancy is categorized as "intermediate-grade," in which disease progression is observed on a monthly basis. In Japan, the percentage of ALCL in malignant lymphomas is from 1.5 to 2.0%1, 2), about half of which have been reported as ALK-positive.3,4) Considering that the 5-year survival rate with successful treatment has been reported to be 60% in patients with ALK-positive ALCL who received chemotherapy in another global study, the percentage of recurrent and refractory cases is estimated to be 40%.3)

Prescribing Information *The underlined parts were newly added.

Product name: Alecensa capsule 150 mg
Nonproprietary name: alectinib hydrochloride
Indications: ○ALK fusion gene positive unresectable, recurrent / advanced non-small cell lung cancer
○Recurrent or refractory ALK fusion gene-positive anaplastic large cell lymphoma
Dosage and administration:
〈ALK fusion gene-positive unresectable, recurrent or advanced non-small cell lung cancer〉
The usual adult dosage is 300 mg alectinib administered orally twice daily.

〈Recurrent or refractory ALK positive anaplastic large-cell lymphoma〉
The usual dosage is 300 mg of alectinib administered orally twice daily. The usual dosage in adults and children weighing less than 35 kg is 150 mg of alectinib administered orally twice daily.

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

Sources

Lymphoma Study Group of Japanese Pathologists. The World Health Organization classification of malignant lymphomas in Japan: Incidence of recently recognized entities. Pathol Int. 2000 Sep; 50(9): 696-702
Aoki R, Karube K, Sugita Y, Nomura Y, Shimizu K, Kimura Y, et al. Distribution of malignant lymphoma in Japan: Analysis of 2260 cases. 2001-2006. Pathol Int. 2008 Mar; 58(3): 174-82
Savage KJ, Harris NL, Vose JM, Ullrich F, Jaffe ES, Connors JM, et al. ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral Tcell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. Blood. 2008 Jun 5; 111(12): 5496-504
Sibon D, Fournier M, Brière J, Lamant L, Haioun C, Coiffier B, et al. Long-Term Outcome of Adults With Systemic Anaplastic Large-Cell Lymphoma Treated Within the Groupe d’Étude des Lymphomes de l’Adulte Trials. J Clin Oncol. 2012 Nov 10; 30(32): 3939-46

On February 21, 2020 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it obtained approval for an additional indication of an anticancer agent/tyrosine kinase inhibitor, Rozlytrek (generic name: entrectinib) for the treatment of ROS1 fusion-positive, unresectable, advanced or metastatic non-small cell lung cancer (NSCLC) from the Ministry of Health, Labour and Welfare (MHLW) (Press release, Chugai, FEB 21, 2020, View Source [SID1234554593]).

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"We are very pleased to announce the approval of Rozlytrek for the treatment in adults with ROS1 fusion-positive NSCLC. Rozlytrek was launched last year as Chugai’s first product to embody advanced personalized healthcare for the treatment of patients with NTRK fusion-positive solid tumors regardless of their age or site of origin," said Dr. Osamu Okuda, Executive Vice President, Co-Head of Project & Lifecycle Management Unit. "ROS1 is an important cancer-driver gene found in 1 to 2% of patients with NSCLC. Offering Rozlytrek as a new treatment option for ROS1 fusion-positive NSCLC patients, we will continue making efforts to contribute to the progress in advanced personalized medicine."

This approval is based mainly on the results of an open-label, multicenter, global phase II STARTRK-2 study. Efficacy was evaluated in ROS1 fusion-positive NSCLC cohort from the STARTRK-2 study while safety was evaluated in two overseas phase I studies (STARTRK-1 study and ALKA-372-001 study) in addition to STARTRK-2 study.

FoundationOne CDx Cancer Genomic Profile is used as a companion diagnostic to identify people that could potentially benefit from Rozlyterk for the ROS1 fusion-positive, unresectable, advanced or metastatic NSCLC. The MHLW granted the approval for the expanded use of FoundationOne CDx Cancer Genomic Profile as a companion diagnostic of Rozlytrek on December 25, 2019.

As a leading company in the field of oncology, Chugai is committed to contribute to patients and medical professionals through realization of advanced personalized healthcare.

[Reference information]
Chugai Obtains Approval for Expanded Use of FoundationOne CDx Cancer Genomic Profile as a Companion Diagnostic of Rozlytrek for ROS1-positive Lung Cancer (A press release issued by Chugai on December 26, 2019)
View Source

Roche’s investigational medicine entrectinib showed a durable response of more than two years in people with a specific type of lung cancer (A press release issued by Roche on September 24, 2018)
View Source

Approval information The underlined part has been newly added.

Product name Rozlytrek Capsules 100 mg
Rozlytrek Capsules 200 mg
Generic name entrectinib
Indications NTRK fusion-positive advanced or metastatic solid tumors
ROS1 fusion gene positive, unresectable, advanced or metastatic non-small cell lung cancer
Dosage and administration
In case of patients with NTRK fusion-positive advanced or metastatic solid tumors.
The usual adult dosage is 600 mg entrectinib administered orally once a day. Reduce the dose as necessary depending on the patient’s condition.
The usual pediatric dosage is 300 mg/m2 (body surface area) entrectinib administered orally once a day. However, the dose should not exceed 600 mg. Reduce the dose as necessary depending on the patient’s condition.
In case of patients with ROS1 fusion gene positive, unresectable, advanced or metastatic non-small cell lung cancer.
The usual adult dosage is 600 mg entrectinib administered orally once a day. Reduce the dose as necessary depending on the patient’s condition.
Conditions for approval
A risk management plan should be created and appropriately implemented.
Given that the number of patients in clinical studies in Japan was extremely limited, post-marketing drug use surveillance of all patients receiving Rozlytrek should be conducted until data for a certain number of patients have been accumulated, in order to understand background information on patients receiving Rozlytrek, collect early data on the safety and efficacy of Rozlytrek, and take necessary measures for appropriate use of Rozlytrek.
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 was approved for the treatment of locally advanced or metastatic solid tumors that harbor NTRK1/2/3 gene fusions in June 18, 2019 and was launched in September 4, 2019.

About ROS1 fusion-positive NSCLC
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 1 to 2% of NSCLC, among which it is more expressed in adenocarcinoma.1)

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

On February 20, 2020 Montis Biosciences reported its launch with €8,4 million in seed financing from an international investor syndicate to investigate interactions between perivascular macrophages and tumor vasculature (Press release, Montis Biosciences, FEB 20, 2020, View Source [SID1234568646]). The company’s mission is to exploit these cellular interactions with therapeutics to drive and sustain immune reactions against solid tumors.

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Montis was founded by Droia Ventures, VIB and KU Leuven based on the foundational science discovered by the labs of Peter Carmeliet (VIB-KU Leuven) and Massimiliano Mazzone (VIB-KU Leuven). For the seed financing, the founders were joined by new investors Polaris Partners, ALSA Ventures and Pfizer Ventures, the venture capital arm of Pfizer Inc. (NYSE: PFE).

Blood vessels regulate the influx of immune cells into tumors. They do so under direction of perivascular macrophages, which can stimulate blood vessels to attract immune cells and let them pass into the tumor, or can induce blood vessel dysfunction and create an immune-compromised environment or suppressive environment in the tumor. Montis’ proprietary insights into how these two classes of cells interact now allows for modulation of these interactions to ensure a strong influx of fresh immune cells into the tumor. The seed financing will allow Montis to prioritize among a set of targets and to validate its lead programs for further development towards clinical studies. Montis will also expand its unique screening and assay platform to identify and validate additional promising targets.

"It is becoming increasingly clear that endothelial cells in the tumor vasculature play a major role in immune reactions to cancer and that their interaction with immune cells shapes this response. Historical therapies targeting the tumor vasculature largely ignored this role and instead destroyed the vessels to starve the tumor," says professor Peter Carmeliet. "Our research is showing that rather than destroying blood vessels, we can use them to herd the correct immune cells to the tumor and get much more potent and sustainable effects."

"Our approach with single-cell RNA-sequence data finally allows us to investigate the communication between immune cells and the tumor vasculature," adds professor Massimiliano Mazzone. "Montis is the step forward to translate this concept into therapeutic applications."

Montis’ Board of Directors will be composed of Executive Chairman and Droia Partner, Luc Dochez, and VIB Head New Ventures, Griet Vanpoucke, who will be joined by Ellie McGuire (Polaris Partners), Sohaib Mir (ALSA Ventures) and Rana Al-Hallaq (Pfizer Ventures).

"We’re very pleased to have been able to bring together the world-class science from the VIB-KU Leuven labs of Peter Carmeliet and Massimiliano Mazzone with an investor syndicate that is excellently positioned to ensure the long-term success of the company," says Luc Dochez, Partner at Droia Ventures and Executive Chairman at Montis. "Montis has a unique approach to target solid tumors that should be able to really shift the paradigm on multiple indications."

"We are excited to work with Droia Ventures in this oncology focused company co-creation effort," comments Johan Cardoen, managing director of VIB. "Montis is a prime example of how scientific excellence complemented with an entrepreneurial mindset and hands-on early stage investors can result in a promising new venture."

On February 20, 2020 Akari Therapeutics, Plc (Nasdaq: AKTX), a biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where the complement and/or leukotriene systems are implicated, reported that it has entered into definitive agreements with certain accredited investors, the majority of whom are existing investors of the Company, including Dr. Ray Prudo, Akari’s Chairman, to receive gross proceeds of approximately $6 million through the private placement of its equity securities (Press release, Akari Therapeutics, FEB 20, 2020, View Source [SID1234555167]).

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In connection with the offering, the Company will issue unregistered American Depository Shares (ADSs) at a purchase price of $1.70 per ADS. Additionally, for each ADS purchased by investors, the investors will receive an unregistered warrant to purchase one-half ADS. The warrants will have an exercise price of $2.20 per ADS, will be exercisable upon their issuance and will expire five years from the issuance date. The closing of the offering is expected to take place during or before the week of February 24, 2020, subject to the satisfaction of customary closing conditions.

Paulson Investment Company, LLC, is acting as the exclusive placement agent in connection with this offering.

The ADS and warrants described above are being offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and, along with the ADSs issuable upon exercise of the warrants, have not been registered under the Act, and may not be offered or sold in the United States absent registration with the SEC or an applicable exemption from such registration requirements.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein. There shall not be any offer, solicitation of an offer to buy, or sale of securities in any state or jurisdiction in which such an offering, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On February 20, 2020 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported that it has received an independent assessment of the absence of cardiotoxicity in patients treated with Annamycin in both its US and European open label and single arm Phase 1 clinical trials (Press release, Moleculin, FEB 20, 2020, View Source [SID1234554627]). Data from the first 5 patients in the US and the first 9 patients in Europe were made available to an expert in chemotherapy who is affiliated with a leading cancer research institute in assessing cardiotoxicity. After review of this data, the independent expert concluded that he "does not see evidence of cardio-toxicity."

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Moleculin Biotech, Inc. is a clinical stage pharmaceutical company focused on the development of a broad portfolio of oncology drug candidates for the treatment of highly resistant tumors. (PRNewsfoto/Moleculin Biotech, Inc.)

The data made available included left ventricular ejection fraction (LVEF) as determined by echocardiograms, ECHO strain imaging, and Troponin levels. For a small population of patients, ECHO strains were not provided due to the limitations of delivery of such data by the clinical sites. "ECHO strain imaging" is a method in echocardiography (medical ultrasound) for measuring regional or global deformation of the myocardium (heart muscle). By strain rate imaging, the simultaneous function of different regions can be displayed and measured. Cardiac health biomarkers such as blood Troponin levels are considered an indicator of potential long-term heart damage.

"We are pleased to receive this independent assessment which further validates the absence of cardiotoxicity in patients to date of Annamycin," stated Wally Klemp, Chairman and CEO of Moleculin. "Currently approved anthracyclines are notoriously cardiotoxic, so demonstrating that Annamycin is not cardiotoxic, even in patients who have received more than the lifetime maximum cumulative anthracycline exposure established by the FDA, supports our claim that Annamycin is truly in a class by itself, and indeed a ‘Next Generation’ anthracycline." He continued, "We are excited to continue to demonstrate Annamycin’s excellent safety profile. We believe continuing to demonstrate the lack of cardiotoxicity, along with initial efficacy data shown while increasing the dosage to a therapeutic level, will make Annamycin an extremely promising new drug candidate."