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Chugai’s HEMLIBRA® Receives Breakthrough Therapy Designation
from U.S. FDA for Hemophilia A without Factor VIII Inhibitors

On April 17, 2018 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for its anti-coagulation factor IXa/X humanized bispecific monoclonal antibody / coagulation factor VIII substitute, "HEMLIBRA" [US generic name: emicizumab-kxwh] for people with hemophilia A without factor VIII inhibitors (Press release, Chugai, APR 17, 2018, View Source [SID1234525404]). Development and distribution of the drug in the US is conducted by Genentech, a member of Roche Group.

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"We are thrilled that HEMLIBRA has been granted its second Breakthrough Therapy Designation," said Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit, Dr. Yasushi Ito. "This will allow us to expedite potential delivery of this new therapy we created to people with hemophilia A without inhibitors in the US following the previous designation for inhibitors. We continue to work closely with Genentech to enable this line extension as soon as possible."

This designation is based on the global phase III HAVEN 3 (NCT02847637) study evaluating HEMLIBRA subcutaneous injection once a week and once every two weeks in people with hemophilia A (12 years of age or older) without inhibitors to factor VIII.

Hemophilia A is a disease presenting repeated severe bleeding symptoms. In this disease, the blood coagulation reaction does not proceed normally due to the deficiency or functional disorder of coagulation factor VIII. For people with hemophilia A without inhibitors, regular factor VIII replacement therapy has been widely used to prevent bleeding. HEMLIBRA is a bispecific monoclonal antibody, which was developed using Chugai’s proprietary antibody engineering technologies. The drug is designed to bind factor IXa and factor X. In doing so, HEMLIBRA provides the cofactor function of factor VIII in people with hemophilia A, who either lack or have impaired coagulation function of factor VIII1, 2). In the HAVEN 3 study, a statistically significant reduction in the frequency of bleeding episodes was observed with HEMLIBRA. With the convenience of subcutaneous administration and the lower frequency of administration, it is expected to be a new treatment option for hemophilia A.
This is the sixth Breakthrough Therapy Designation received for three drugs created by Chugai: ALECENSA (ALK-positive non-small cell lung cancer with disease progression on crizotinib, and first line treatment for ALK-positive non-small cell lung cancer), ACTEMRA (systemic sclerosis and giant cell arteritis), and HEMLIBRA (prophylactic treatment for patients 12 years or older with hemophilia A with factor VIII inhibitors).

Trademarks used or mentioned in this release are protected by law.
References
Kitazawa, et al. Nature Medicine 2012; 18(10): 1570
Sampei, et al. PLoS ONE 2013; 8: e57479
About Breakthrough Therapy
Breakthrough Therapy Designation was adopted as part of the FDA Safety and Innovation Act (FDASIA) enacted in July 2012 aiming at expediting the development and review of drugs for the treatment of severe or life-threatening diseases or symptoms. In order to grant Breakthrough Therapy Designation, preliminary clinical evidence is required demonstrating that the drug may have substantial improvement on at least one clinically significant endpoint over existing therapies. Breakthrough Therapy Designation includes the features of a Fast Track designation, with the addition of intensive guidance on efficient drug development as well organizational commitment from FDA.
Main approval status of the drug

US: In November 2017, the drug (US product name: HEMLIBRA; Genentech) was approved by the U.S. Food and Drug Administration and was marketed for "routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors."

EU: In Europe, the drug (EU product name: HEMLIBRA; Roche) obtained regulatory approval from the European Commission and was marketed for routine prophylaxis of bleeding episodes in people with hemophilia A with factor VIII inhibitors in February 2018.
Japan: The Ministry of Health, Labour and Welfare has approved HEMLIBRA for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with congenital factor VIII deficiency (hemophilia A) with factor VIII inhibitors in March 2018.
About the results of HAVEN 3 study
Press release issued on November 20, 2017
View Source

Taiho Pharmaceutical and Helsinn Group present preclinical data at AACR Annual Meeting for a RET inhibitor under co-development as an attractive compound for anticancer therapy

On April 16, 2018 Taiho Pharmaceutical Co., Ltd., a Japanese R&D-driven specialty pharma focused on oncology and Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, reproted that they are collaborating on the development of an investigational highly-selective RET inhibitor TAS0286/HM05, being evaluated in non-small cell lung cancer and other carcinomas (Press release, Helsinn, APR 16, 2018, View Source [SID1234561171]). Preliminary data regarding TAS0286/HM05 is being presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting in Chicago, Illinois, U.S.A. Abstracts of the presentations are available at: View Source!/4562/presentation/6785

In in-vitro preclinical studies, TAS0286/HM05 inhibited the proliferation of various RET fusions and RET-activating mutations positive cells as well as in in-vivo preclinical studies, TAS0286/HM05 was shown to significantly inhibit the growth of tumors harboring various RET fusions and activating mutations at a range of 20 to 100 mg/kg/day without any body weight loss. The antitumor efficacy of TAS0286/HM05 was more potent than pre-existing multikinase inhibitors at their maximum tolerated dose. Primary data in mice studies has shown an effect in tumor growth, providing an induced tumor regression of 40% within 15 days. This study is being presented as a poster on Tuesday, April 17 from 1:00 PM to 5:00 PM CST in Poster Section 36, Poster Board Number 13 (Abstract No. 4784).

"Preliminary data for TAS0286/HM05 suggests it may be a potential agent for future clinical development in patients with RET gene abnormalities," Sergio Cantoreggi, Helsinn Group Chief Scientific Officer commented. "Helsinn and Taiho Pharmaceutical have collaborated over many years on a number of programs and we are delighted to be able to present this promising preclinical data, and we look forward to further collaboration."

"Over the years, Taiho Pharmaceutical has collaborated with Helsinn as an excellent partner in the development and marketing of new drugs. I am excited about the new collaboration with Helsinn on the selective RET inhibitor that was discovered by the Taiho Tsukuba Research Center. I look forward to the success of the program and the strengthening of our partnership." Teruhiro Utsugi, Taiho Managing Director commented.

TAS0286/HM05 was discovered by Taiho Pharmaceutical and it will now be jointly developed by Helsinn and Taiho Pharmaceutical. TAS0286/HM05 is an investigational agent and is not approved for commercial use in any country.

Clinical Trial Tests ONC201 in Combination with Ixazomib and Dexamethasone in Multiple Myeloma

On April 16, 2018 Oncoceutics, Inc. reported that the first patient has been treated in a Phase I/II clinical trial of ONC201 in combination with ixazomib and dexamethasone in relapsed and/or refractory multiple myeloma (Press release, Oncoceutics, APR 16, 2018, View Source [SID1234558369]). The trial, led by Ajai Chari, MD, Associate Professor at the Icahn School of Medicine at Mount Sinai, is entitled "A Phase I/II Study of the Addition of Ixazomib to ONC201 and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma" (NCT03492138) and seeks to combine two oral medications that have shown synergy against multiple myeloma in preclinical models. The study will enroll up to 36 adult patients and will evaluate the safety and tolerability of ONC201 in combination with ixazomib and dexamethasone in Phase I and determine the two-month disease control rate as the primary endpoint of Phase II.

While Oncoceutics is currently focused on clinical trials of ONC201 in high-grade gliomas as its lead indication, the company continues to advance a number of clinical programs in B cell malignancies because they have shown some of the highest sensitivity against ONC201 in pre-clinical models. Oncoceutics currently has two programs in multiple myeloma: "Oral ONC201 in Relapsed/Refractory Multiple Myeloma" (NCT02863991) and the combination trial with ixazomib described above.

Multiple myeloma is highly sensitive to proteasome inhibitors that activate the integrated stress response, the same pathway activated by ONC201 treatment through unique triggers. ONC201 synergizes with proteasome inhibitors since they converge on some of the same downstream effects as ONC201 even though they use distinct triggers in tumor cells. Based on this rationale, which is supported by published preclinical studies (Prabhu et al, Cell Cycle 2018; Tu et al, Neoplasia 2017), this clinical trial will test the combination of ONC201 with ixazomib and dexamethasone. Ixazomib, which goes by brand name NINLARO, is an oral proteasome inhibitor developed by Takeda Pharmaceutical Company. It is FDA approved in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. In addition to the U.S., NINLARO is approved in more than 50 countries.

"We are excited to have the opportunity to test these two oral agents that have demonstrated efficacy against multiple myeloma in pre-clinical settings to provide therapies to patients with refractory/relapsed multiple myeloma that are in need of novel therapies," said Ajai Chari, Associate Professor, Medicine, Hematology and Medical Oncology, at the Icahn School of Medicine at Mt. Sinai.

Nordic Nanovector Presents Preclinical Data at AACR 2018

On April 16, 2018 Nordic Nanovector ASA (OSE: NANO) reported that a poster reporting the anti-tumour effect of Humalutin (177Lu-conjugated humanized anti-CD37 antibody, 177Lu-NNV003) in preclinical models of non-Hodgkin’s lymphoma (NHL) was presented yesterday at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 in Chicago, USA (Press release, Nordic Nanovector, APR 16, 2018, View Source [SID1234553507]). The company previously announced the publication of the poster abstract (abstract 848) on 15 March 2018.

The poster was entitled "In vitro and in vivo evaluation of the beta-emitting lutetium-177 labeled anti-CD37 antibody radionuclide conjugate 177Lu-NNV003 in DLBCL, CLL and MCL models," and showed that:

In tumour cell lines:

• The unlabelled anti-CD37 antibody (NNV003) kills tumour cells mainly through an immunological process called antibody dependent cellular cytotoxicity

• Humalutin (177Lu-NNV003) was found to inhibit tumour cell growth.

In preclinical lymphoma models:

• Humalutin has shown significant tumour uptake and demonstrated an anti-tumour effect in all three NHL models (mantle cell lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukaemia).

Phoenix Molecular Designs Announces Manufacturing Collaboration with WuXi STA to advance PMD-026 toward IND

On April 16, 2019 Phoenix Molecular Designs (PhoenixMD), a privately-held biotechnology company designing precise cancer therapeutics by targeting essential kinases, reported that it has entered into a collaboration with STA Pharmaceutical Co., Ltd (STA), a WuXi AppTec group company, to manufacture the PMD-026 needed for IND-enabling toxicology studies and a Phase I study in women (Press release, Phoenix Molecular Designs, APR 16, 2018, View Source [SID1234536961]).

Under the terms of the collaboration agreement, STA will become a new manufacturing partner for PhoenixMD for their platform of kinase inhibitor drug candidates to treat a wide range of unmet medical needs, with an initial focus on triple negative breast cancer (TNBC). STA will be responsible for the early manufacturing work through their GMP-certified site in San Diego, CA. Through these collaborative efforts, PhoenixMD expects to file an Investigational New Drug Application (IND) with the U.S. Food and Drug Administration (FDA) for PMD-026.

Dr. Minzhang Chen, CEO of STA, commented, "We are excited to manufacture PMD-026 and enable Phoenix MD to advance this novel RSK inhibitor to shrink tumors in Phase 1 studies in women."

"We’re thrilled to collaborate with STA, a global leader in drug development and manufacturing, who has helped us achieve an important milestone in the efficient and scalable manufacturing of PMD-026," said Sandra E. Dunn, CEO PhoenixMD. "Through this work, we have demonstrated that PMD-026 has the potential to be disease-modifying with its ability to block the RSK pathway signaling and initiating significant tumor shrinkage of up to 70% in TNBC xenograft models. Looking ahead, we expect to build upon this progress and file an IND for PMD-026, with the ultimate goal of confirming these revolutionary results in women suffering from TNBC."

Gerrit Los, CSO of PhoenixMD added, "It is critical to have a manufacturing partner at this stage of development for PMD-026. This collaboration will allow us to move PMD-026 into IND enabling toxicology studies and to get ready for a successful IND filing. Importantly, it provides us the security to have access to GMP quality API when we are ready to start our Phase I study."

About Triple Negative Breast Cancer (TNBC) and RSK Kinases

Approximately 400,000 cases of TNBC are diagnosed every year worldwide and it is one of the most difficult breast cancer subtypes to treat due to lack of effective, targeted therapies. TNBC also claims the lives of young women more than any other type of breast cancer due to a lack of understanding around the therapeutic bullseye. It is also a very heterogeneous disease, therefore a common denominator across TNBC types was necessary to identify the bullseye. Through genome-wide screens, RSK was identified as the prime target for TNBC by scientists at PhoenixMD. Currently, there are still no targeted therapies available for TNBC.

There are four types of RSK involved in cancer, known as RSK1-4, and each type has a unique role in the development of the disease. RSK1 is responsible for cancer cell invasion and is an important driver in the spread of cancer. RSK2 controls cancer cell growth, and RSK3 and RSK4 are associated with drug resistance.

RSK1 and RSK2 have been proven critical to the survival of patients with TNBC. Over 90% of primary TNBC express high levels of RSK1 and RSK2. Inhibiting RSK2 eliminates TNBC cells completely, including cancer stem cells, which give rise to cancer recurrence. PhoenixMD, with its novel, targeted approach, is focused on creating patented cancer RSK inhibitors and companion diagnostics for cancer indications – initially in breast cancer – with the potential to treat blood, brain, ovarian, lung, skin, prostate, colon, head and neck cancers.

Currently, there are no approved targeted therapies for TNBC, although several drugs are subject to research studies and clinical trials. PhoenixMD is addressing this unmet medical need through a novel, targeted approach by inhibiting critical kinases, such as RSK1-4, a group of highly conserved Ser/Thr kinases that promote cell proliferation, growth, motility and survival. For this target, PhoenixMD developed PMD-026, a first-in-class, specific RSK inhibitor that blocks downstream signaling of RSK and induces apoptosis.