1stOncology™: Cancer Intelligence Service – Page 16120 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

[PDF]Kyowa Hakko Kirin Announces Initiation of Phase 3 Study in Japan of Mogamulizumab in Patients with HTLV-1 Associated Myelopathy

On June 30, 2017 Kyowa Hakko Kirin Co., Ltd. (Headquarters:Tokyo; President and CEO: Nobuo Hanai, "Kyowa Hakko Kirin") announces that it has initiated a Phase 3 clinical study in Japan of mogamulizumab (code No. : KW-0761)*1 in patients with HTLV-1-associated myelopathy (Press release, Kyowa Hakko Kirin, JUN 30, 2017, View Source [SID1234519735]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

HTLV-1-associated myelopathy (HAM) manifests as inflammation in the spinal cord caused by T-lymphocytes infected with human T-cell leukemia virus type 1 (HTLV-1). The disease progresses slowly and is accompanied by symptoms such as walking difficulties, numbness, difficulty passing urine, and constipation. A 2010 epidemiological survey estimated that approximately 3,000 patients in Japan have developed HAM, where it is a designated intractable disease*2. Mogamulizumab is a humanized monoclonal antibody targeting CC chemokine receptor 4 (CCR4).

Mogamulizumab utilizes its enhanced ADCC activity to eliminate CCR4-positive T-lymphocytes infected with HTLV-1, and therefore is expected to alleviate symptoms in patients with HAM. Kyowa Hakko Kirin started the Phase 3 study based on the results of the investigatorinitiated clinical trials (Phase 1/2a study (completed) and the long-term study (ongoing)) led by Dr. Yoshihisa Yamano, Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine. The purpose of the Phase 3 study is to evaluate the efficacy and safety of mogamulizumab in patients with HAM.

"HAM is a severe disease which causes long term myelopathic symptoms, such as lower limb paralysis, pain, dysuria, and constipation, and for which there are no currently effective treatments." said Mitsuo Satoh, Ph.D., Head of Research and Development Division of Kyowa Hakko Kirin. "We hope mogamulizumab will be a treatment option for patients with HAM."

The Kyowa Hakko Kirin Group companies strive to contribute to the health and wellbeing of people around the world by creating new value through the pursuit of advances in life sciences and technologies.

News Release

Target Disease HTLV-1-associated myelopathy (HAM)
Design Randomized, double-blind, placebo-controlled study with an open label study
Target number of subjects 52
Primary endpoint Improvement in the Osame’s Motor Disability Score (OMDS)
Publicized information ClinicalTrial.gov: NCT03191526 *1

About mogamulizumab (KW-0761)
Mogamulizumab is a humanized monoclonal antibody targeting CC chemokine receptor 4 (CCR4). CCR4 is frequently expressed in certain hematologic cancer cells, but also expressed in T-lymphocytes infected with HTLV-1. Mogamulizumab is manufactured using Kyowa Hakko Kirin’s POTELLIGENT technology that is related to increased ADCC activity. It was approved for sale for the first time globally in Japan, and since March 2012 has been sold as an approved drug (brand name: POTELIGEO) for relapsed or refractory CCR4-positive adult T-cell leukemia-lymphoma (ATL). Furthermore, mogamulizumab obtained approval for additional indications in Japan for relapsed or refractory CCR4-positive peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) in March 2014 as well as for chemotherapy-naïve CCR4-positive ATL in December 2014. *2

About designated intractable diseases
Designated intractable diseases are diseases covered by medical subsidies as set forth in Article 5 of the Law for Medical Treatment of Patients with Intractable Diseases enacted in May 2014 in Japan. The designation is made by the Minister of Health, Labor, and Welfare when quality and appropriate medical treatment are judged to be imperative for patients with such a disease based on the opinion of the Health Science Council.

Cytovation announces private fundraising round of NOK 20m to progress CyPep-1 to Phase 1 clinical study

On June 29, 2017 Cytovation AS, a privately held biotech company developing CyPep-1 for the treatment of skin disorders, reported that it has raised NOK 20m in a private funding round. The financing was led by a group of private investors in Norway and the Company will use these funds to advance lead product CyPep-1 into a Phase I clinical trial (Press release, Cytovation, JUN 29, 2017, View Source [SID1234561558]).

Cytovation is developing CyPep-1, a peptide consisting of 27 amino acids that selectively targets cutaneous warts through the destruction of the cell membrane and creating an immune response through the release of antigens. These funds will enable Cytovation to conduct pre-clinical toxicology studies and GMP manufacturing of CyPep-1 as a topical cream for the treatment of warts caused by the human papilloma virus (HPV). This is a completely novel treatment strategy to treat a common disease which has already undergone extensive testing and quality control and also has applications in other dermatological diseases.

Cytovation’s CEO, Kjell Inge Arnevig, commented on the financing: "We have been encouraged by the continuing support of our new and existing investors. These funds will allow us to move through toxicology studies and formulation towards our planned Phase I clinical trial for CyPep-1 with initial results expected during 2018."

CRT’s Discovery Laboratories extends alliance with Merck to develop new cancer drugs

On June 29, 2017 CANCER RESEARCH TECHNOLOGY (CRT) reported that it has signed a further deal with Merck, a leading science and technology company, to discover new cancer drugs targeting the Hippo pathway, today (Thursday) (Press release, Cancer Research Technology, 29 29, 2017, View Source [SID1234523164]).

The extension to this alliance follows a successful one-year target validation and drug discovery feasibility partnership between CRT’s Discovery Laboratories (CRT-DL) in London and Cambridge and Merck at Darmstadt in Germany.

In conjunction with Cancer Research UK’s network of key academic scientists, led by Dr Nic Tapon and Dr Barry Thompson, based at the Francis Crick Institute in London, the alliance has developed a better understanding of the role of the Hippo pathway in cancer, and how best to drug key targets.

In healthy cells the Hippo pathway regulates cell size, controlling the growth of tissues during development and regeneration. But, abnormal activation of proteins controlled by the Hippo pathway has been linked to the development of a range of cancers, making it an attractive area for the discovery of novel therapies.

The partnership has now moved into full drug discovery with the aim of eventually identifying molecules to take into preclinical studies and clinical trials. Dr Tapon will remain a key participant in the alliance moving forwards.

CRT will receive royalties and milestone payments from the deal to be invested into Cancer Research UK’s lifesaving research.

Dr Iain Foulkes, Cancer Research Technology’s chief executive, said: "The extension and expansion of this alliance showcases the success of Cancer Research Technology’s Discovery Laboratories drug discovery approach in moving forward exciting new approaches to cancer therapy. We’ve brought together leading academics in the field and industry to build on world-class research, and we’re now focused on developing these early projects for the benefit of cancer patients."

Dr Hamish Ryder, Cancer Research Technology’s director of drug discovery, said: "This important research highlights our expertise in applying translational thinking to novel, very early stage science."

Servier and Transgene have become partners to apply viral vectorization technology to the engineering of allogenic CAR-T

On June 29, 2017 Servier and Transgene (Euronext Paris: TNG), a biotechnology company that designs and develops immunotherapies based on viral vectors, reported the signature of a research agreement on the application of viral vectorization technology for the production of allogenic CAR-T cell therapies (Press release, Transgene, JUN 29, 2017, View Source [SID1234519742]). The aim is to obtain more efficient products for patients.

"Allogenic cell therapies using CAR-T open a major field of innovation in the treatment of cancer," stated Patrick Therasse, Oncology Research and Development Director at Servier. "However, each of the steps in their complex manufacturing process requires specific development and optimization efforts, in order to provide patients with the best possible therapeutic options. And we look for the best partners to move these products forward. ".

The aim of the collaboration between the scientific teams at both Servier and Transgene is to evaluate and select innovative vectorization methods based on Transgene’s viral vector collection, which may be applied to the engineering of CAR-T cell therapies. In addition to the development of simpler, faster and more effective methods, the aim is also to obtain a tighter control of the modified genome areas. Servier and Transgene thus aim to achieve an original allogenic CAR-T preparation method with better transgene integration yields and fewer steps.

Servier has been engaged in the development of cell therapies since November 2015 (see About UCART19).

Transgene has a large collection of viral vectors and is renowned for its competence in the genome engineering of these vectors. These assets will be used to develop new vectorization tools that will allow us to increase the possibility of fine and precise modification of the genome of CART cells, in order to adapt these cells’ properties to the tumor environment and improve the therapeutic efficacy.

Eric Quéméneur, Scientific Director of Transgene, explains: "We are proud of the recognition of our vectorization know-how and of our capacity for innovation by a pharmaceutical company of importance such as Servier. We will enthusiastically contribute to the development of CAR-T, these new promising products in cancer immunotherapy. Thanks to this collaboration, Transgene broadens the domain of the application of viral vectors from its technological platform. ".

"Cellectis is pleased about Servier and Transgene’s collaboration on allogenic CAR-T cell therapies, stated André Choulika, Chairman and Chief Executive Officer of Cellectis. "Transgene stands among the most advanced companies in the world in the development of vector technologies. We are convinced that this collaboration on these cell therapies will lead to ways to optimize production, costs, and potentially explore their use in other leukemia indications".

Transgene may receive more than 30 million Euro for this contract, with an initial duration of three years. As for Servier, it will be able to use these new vectors to develop its cell immunotherapy portfolio.

Chi-Med and AstraZeneca Initiate SAVOIR, a Global Phase III Trial of Savolitinib in Papillary Renal Cell Carcinoma

On June 29, 2017 Chi-Med and AstraZeneca reported that they have initiated a global pivotal Phase III, open-label, randomized multi-center registration study of the highly selective inhibitor of c-MET receptor tyrosine kinase, savolitinib, in c-MET-driven papillary renal cell carcinoma ("PRCC") (Press release, Hutchison China MediTech, JUN 29, 2017, http://www.chi-med.com/initiate-savoir-global-ph3-of-savolitinib-in-prcc/ [SID1234519740]). This is the first pivotal study ever conducted in c-MET-driven PRCC and the first molecularly selected trial in renal cell carcinoma ("RCC").

"The launch of the SAVOIR trial, designed to support product registration in the U.S. and Europe, continues to advance our strategy to deliver innovative medicines to major markets worldwide," said Christian Hogg, Chief Executive Officer of Chi-Med. "Based on the results of our Phase II study, we believe savolitinib has the potential to bring meaningful clinical benefit to patients with c-MET-driven PRCC. We also expect to further understand the correlations between c-MET alterations and patient outcomes through epidemiological analyses using our newly developed companion diagnostic assay."

Susan Galbraith, SVP IMED Oncology, AstraZeneca commented that "It is exciting to achieve this milestone in savolitinib’s development. The data building across our early development studies are encouraging, that savolitinib has the potential to be an important treatment option for c-MET driven cancers including kidney, lung and gastric cancers."

The initiation of this Phase III trial has triggered a US$5 million milestone payment to Hutchison MediPharma Limited (a 99.8% subsidiary of Chi-Med) from AstraZeneca under the terms of the license and collaboration agreement signed between them in 2011 (as amended).

In addition to SAVOIR, Chi-Med and AstraZeneca are conducting a number of Phase Ib and II studies of savolitinib in kidney cancer, lung cancer and gastric cancer. These studies involve savolitinib as a monotherapy or in combination with other targeted therapy, such as Tagrisso (osimertinib) or Iressa (gefitinib). Additional studies combining with Imfinzi (durvalumab) and Taxotere (docetaxel) are also in progress.

About SAVOIR
SAVOIR is a global Phase III, open-label, randomized, controlled trial evaluating the efficacy and safety of savolitinib, compared with sunitinib, in patients with c-MET-driven, unresectable, locally advanced or metastatic PRCC. Approximately 180 patients will be randomized at 50 to 75 sites across five to ten countries. c-MET status is confirmed by the novel targeted next-generation sequencing (NGS) assay developed for savolitinib. Patients will be randomized in a 1:1 ratio to receive either continuous treatment with savolitinib 600 mg (400 mg if <50 kg) orally, once daily, or intermittent treatment with sunitinib 50 mg orally once daily (4 weeks on/2 weeks off), on a 6-week cycle.

The primary objective is to evaluate the primary efficacy endpoint progression free survival ("PFS") of savolitinib as compared with sunitinib. Secondary endpoints include overall survival, objective response rate ("ORR"), duration of response, best percentage change in tumor size, disease control rate, and safety and tolerability. The impact of savolitinib compared with sunitinib on disease symptoms and quality of life, along with the pharmacokinetics of savolitinib will also be assessed. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT03091192.

About Savolitinib
Savolitinib (AZD6094/HMPL-504) is a potential first-in-class selective inhibitor of c-MET (also known as mesenchymal epithelial transition factor) receptor tyrosine kinase, an enzyme which has been shown to function abnormally in many types of solid tumors. It was developed as a potent and highly selective oral inhibitor specifically designed to address issues observed in the clinic with other selective c-MET inhibitors, such as renal toxicity.

Savolitinib was discovered by Chi-Med and is being developed in collaboration with AstraZeneca. Savolitinib is currently being studied in multiple tumor types worldwide including kidney, lung and gastric cancers, both as a monotherapy or in combination with other targeted and immunotherapy agents.

About c-MET-Driven PRCC
Worldwide, about 366,000 new patients are diagnosed with kidney cancer annually. RCC accounts for approximately 80-85% of kidney cancer and has several histological sub-types with different genetic and biochemical characteristics. PRCC is the most common of the non-clear cell renal carcinomas accounting for 10-15% of RCC. However, the biology and molecular characteristics of PRCC are different from those of clear cell RCC ("ccRCC"). Multiple studies indicate that PRCC is c-MET-driven in 40-70% of patients.

There are no therapies approved for patients with PRCC, who currently receive treatments approved for RCC such as sunitinib. These RCC agents were mostly approved on the basis of studies where the majority of subjects were ccRCC patients and where the benefits to the PRCC minority were more modest. Currently the National Comprehensive Cancer Network Guidelines advise PRCC patients to enter clinical trials.

About Savolitinib in PRCC
In February 2017, the results of a global Phase II multicenter study in advanced PRCC was presented at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium, which indicated a clear efficacy signal with savolitinib monotherapy in c-MET-driven patients. Median PFS of 6.2 months in c-MET-driven patients as compared with 1.4 months (p<0.0001) in c-MET-independent patients. ORR was 18.2% in c-MET-driven patients vs. 0% (p=0.002) in c-MET independent patients. An encouraging durable response and safety profile were reported in savolitinib treated patients. Further details are available at www.chi-med.com/asco-gu-2017-savolitinib-ph2-in-prcc-pres/.

Studies of c-MET-driven disease in gastric cancer and lung cancer suggest that c-MET amplification and/or overexpression can be a negative prognostic for disease progression. Over the course of 2017, Chi-Med and AstraZeneca are also conducting a comprehensive molecular epidemiology study of approximately 300 PRCC patient samples to further understand the correlations between c-MET alterations and patient outcomes, including any predictive biomarkers.