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GigaGen and Trianni Announce License Agreement for Discovery of Fully Human Immuno-Oncology Antibodies

On February 28, 2017 GigaGen Inc., a biopharmaceutical company with patented technology for discovery of antibody therapeutics from millions-diverse immune repertoires, reported a strategic partnership with Trianni, Inc., a biotechnology company that has developed novel mouse strains genetically engineered to express human antibodies (Press release, GigaGen, FEB 28, 2017, View Source [SID1234520618]). The partnership will use GigaGen technology to discover immuno-oncology antibody therapeutics through The Trianni Mouse platform.

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"The combined power of the Trianni and GigaGen technologies will produce an unprecedented pipeline of fully-human antibodies," said Dave Johnson, PhD, MBA, CEO of GigaGen. "We are confident that the resulting portfolio will have an enormous impact on the field of immuno-oncology."

The Trianni Mouse has been engineered with genetic loci that are optimized for the expression of antibodies that are entirely human in their variable domains. Because they retain mouse constant regions in their antibody repertoires, the mice are not immunocompromised, but rather exhibit robust lymphocyte development and immune responses.

GigaGen’s highly efficient immune repertoire sequencing and expression platform captures full B-cell repertoires and then builds protein display libraries from the repertoires to rapidly validate binding and function. Using GigaGen’s technology, a single mouse produces hundreds or thousands of therapeutic candidates, which are rapidly sequenced and validated for binding affinity.

"We are excited to put The Trianni Mouse into the hands of our partners at GigaGen," said David Meininger, PhD, MBA, CBO of Trianni. "In prior roles in research and in business development, I evaluated many antibody discovery technologies, and believe that GigaGen and Trianni have transformative technologies that together offer enormous potential to rapidly identify new immuno-oncology treatments."

About Trianni, Inc.
Trianni is a privately held organization, formed in 2010, with a mission to use recent advances in DNA synthesis and genomic modification technology for the development of an optimized therapeutic antibody discovery platform, The Trianni Mouse. The company is headquartered in San Francisco, CA.

4SC to present supportive preclinical data on resminostat’s potential as maintenance therapy for CTCL

On 28 February 2017 4SC AG (4SC, FSE Prime Standard: VSC) will present supportive preclinical data on the potential of the histone deacetylase (HDAC) inhibitor resminostat as maintenance therapy for advanced-stage cutaneous T-cell lymphoma (CTCL) at two conferences (Press release, 4SC, FEB 28, 2017, View Source [SID1234518602]).

There are two HDAC inhibitors currently available in the U.S. to treat CTCL, but these are indicated only for treatment of patients with progressive disease and not for maintenance therapy. 4SC is currently enrolling advanced-stage CTCL patients in the RESMAIN pivotal study in 11 European countries to evaluate resminostat as maintenance therapy which could be an important additional therapeutic option for clinicians and patients.

The data presented at the following two conferences highlight the mechanistic rationale for pursuing a maintenance indication.

Epigenetics in Drug Discovery Session, Advances in Drug Discovery Conference
Poster: Resminostat – an epigenetic approach for CTCL maintenance treatment
Date: 6-7 March 2017
Location: Cambridge, United Kingdom

Clinical Epigenetics International Meeting
Poster: Resminostat – an epigenetic approach for CTCL maintenance treatment
Date: 9-10 March 2017
Location: Dusseldorf, Germany

Abstract summary

Progression of CTCL appears to be associated with a transition from Th1 to Th2 T-helper cell status that is related to altered expression of STAT4/STAT6. Resminostat’s ability to (1) induce apoptosis in several CTCL cell lines and (2) impact on STAT4/STAT6 expression were evaluated in preclinical experiments.

Resminostat demonstrated anti-tumor activity in CTCL cells at clinically relevant doses. Resminostat also increased STAT4 expression and decreased STAT6 expression, suggesting a stabilization of the less advanced CTCL stage (Th1) or even a reconversion of the advanced Th2 to the Th1 phenotype.

The poster will be published on 4SC’s website on Monday, 6 March 2017.

Related articles

24 January 2017, Overall survival benefit for resminostat in first-line liver cancer study subgroup

16 December 2016, First patient enrolled in pivotal RESMAIN study of resminostat in CTCL

16 June 2016, Resminostat boosts cancer immunotherapy

About cutaneous T-cell lymphoma (CTCL)

CTCL is a rare disease with approximately 5,000 patients being newly diagnosed in Europe each year. The disease arises from malignant transformation of T cells, a specialized subgroup of immune cells, primarily affects the skin, but may ultimately involve lymph nodes, blood and visceral organs.

Currently, CTCL is not curable and treatment options for advanced-stage CTCL are limited. Although patients respond to the available treatment options, the duration of response is often short-lived and declines as the severity of the disease increases. The key therapeutic challenge in advanced-stage CTCL is therefore to make remissions more durable, halting disease progression, improving quality of life and prolonging progression free and overall survival.

About the RESMAIN study – Resminostat for maintenance treatment of CTCL

The RESMAIN pivotal study is open for recruitment since November 2016 and is being conducted at more than 50 clinical centers in 11 European countries. It will include 150 patients who suffer from advanced-stage cutaneous T-cell lymphoma (CTCL) and have achieved disease control with systemic therapy. The patients are randomized 1:1 to receive either resminostat or placebo. Patients who experience disease progression – while being on placebo – will be offered resminostat in an open label treatment arm.

The primary goal of the study is to determine whether maintenance treatment with resminostat prolongs progression-free survival and the key secondary objective is to prolong the time to symptom worsening (itching). A comprehensive biomarker program is also included in the study to ensure vital knowledge about the biological background of resminostat treatment and CTCL is acquired. 4SC anticipates top-line data to be available in 2019.

About Resminostat

Resminostat is an orally administered histone deacetylase (HDAC) inhibitor with an epigenetic mechanism of action that potentially offers a novel approach to treating a wide variety of cancers, both as monotherapy and – in particular – in combination therapy with other anti-cancer drugs. As an inhibitor that blocks HDAC classes I, IIB and IV, resminostat can potentially offer benefit to patients as it inhibits tumor growth and proliferation, causes tumor regression, and strengthens the body’s own immune response to cancer.

Resminostat has been shown to be well tolerated in patients with advanced cancers in Phase I studies. Its use in the treatment of cutaneous T-cell lymphoma (CTCL), Hodgkin’s lymphoma and liver, lung, colon, pancreatic and biliary tract cancers has been and is being investigated in further clinical studies. Initial positive efficacy results for resminostat have – amongst others – been observed in combination with the standard medication sorafenib in selected patients with advanced liver cancer (hepatocellular cancer, HCC).

Baxter and ScinoPharm Announce Exclusive Strategic Partnership for Generic Oncology Injectables

On February 28, 2017 Baxter International Inc. (NYSE: BAX) and ScinoPharm Taiwan, Ltd. (TWSE: 1789) reported a strategic partnership to develop, manufacture and commercialize five injectable drugs used in a range of cancer treatments, including lung cancer, multiple myeloma and breast cancer, as well as medication to treat nausea and vomiting, common side effects of chemotherapy (Press release, Baxter International, FEB 28, 2017, View Source [SID1234517907]). The arrangement also provides Baxter the option to partner with ScinoPharm—one of the world’s leading active pharmaceutical ingredient (API) manufacturers—on as many as 15 additional injectable molecules.

Under the terms of the partnership, Baxter and ScinoPharm will collaborate on product development and manufacturing. Baxter will hold commercialization rights, with products included in the arrangement expected to launch beginning in 2020.

"Combining Baxter’s differentiated manufacturing expertise and global commercialization capabilities with ScinoPharm’s recognized API experience enables Baxter to increase patient access to difficult-to-manufacture, high-quality oncolytic medicines," said Robert Felicelli, president, Pharmaceuticals, Baxter. "The ScinoPharm collaboration will further expand Baxter’s presence in generic injectables, which will continue to be enhanced through our recently executed agreement to acquire Claris Injectables Limited."

Current branded sales of the initial five products included in this partnership total more than $4 billion annually. These products will join Baxter’s existing portfolio of generic injectable medications, which includes difficult-to-manufacture oncology drugs and a broad portfolio of standard-dose, ready-to-use premixed injectable products such as anti-infectives, analgesics and critical care medicines.

ScinoPharm has a 17-year history of manufacturing APIs for the global pharmaceutical industry with a high level of quality and safety. Under the arrangement, ScinoPharm will provide APIs for the initial five generic injectables, and Baxter and ScinoPharm will share manufacturing responsibilities, with the majority of the molecules to be manufactured at Baxter’s state-of-the-art facility in Halle, Germany, one of the most advanced facilities in the world for manufacturing oncology drugs.

"We are very excited to partner with Baxter. We bring complementary strengths to this arrangement that will ultimately lead to more injectable oncology products on the market," said ScinoPharm CEO Dr. Yung Fa Chen. "This strategic partnership will boost our expansion in the formulation business, increase market coverage of our products and eventually fuel our further operating performance."

Commencement of Phase 1 Trial for the Mutant IDH1 Inhibitor (DS-1001) Targeting Malignant Brain Tumors

On March 1, 2017 The National Cancer Center of Japan and Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported a collaboration to develop an inhibitor for mutant isocitrate dehydrogenase IDH1 (DS-1001) as a new molecular targeting drug for malignant brain tumors (gliomas)*1 and the commencement of a first-in-human phase 1 clinical trial*2 (Press release, Daiichi Sankyo, FEB 28, 2017, View Source [SID1234517902]).

Mutations in the IDH1 and IDH2 genes are frequently observed in patients with malignant tumors, such as gliomas, acute myeloid leukemia (AML), cholangiocarcinoma, and chondrosarcoma. The National Cancer Center Research Institute, Division of Hematological Malignancy research group led by Issay Kitabayashi discovered that inhibitions of mutant IDH1/2 were able to eliminate AML cancer stem cells*3. In addition, preclinical studies using patient-derived xenograft (PDX) models*4 showed that DS-1001, which has high blood-brain barrier permeability, was effective in suppressing the proliferation of malignant gliomas, AML, and chondrosarcoma.

Most molecular targeted drugs developed to date target molecules that are active or highly expressed in tumors. However, these drugs may have problematic side effects because the targeted molecules are to some extent also active in normal, healthy cells. DS-1001 selectively inhibits the mutant form of IDH1, which is expressed only in cancer cells, and has minimum effect against wild-type IDH1, which is expressed in normal cells.

Mutations in the IDH1 genes are observed in more than 70% of patients who are diagnosed as grade 2 or 3 gliomas (astrocytomas or oligodendrogliomas) *5. These types of glioma with IDH1 mutation are most frequently observed in 30 to 50 years old population, with multiple relapse and long term treatment course*6. DS-1001 may be effective in such a patient population.

This multicenter phase I clinical trial is planned to enroll patients with recurrent IDH1 mutant gliomas who have no standard treatment at the National Cancer Center Hospital (Chuo-ku, Tokyo) and other facilities in Japan.

TRACON Pharmaceuticals Reports Fourth Quarter and Year-End 2016 Financial Results and Provides Corporate Update

On February 28, 2017 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age‐related macular degeneration and fibrotic diseases, reported financial results for the fourth quarter and year ended December 31, 2016 (Press release, Tracon Pharmaceuticals, FEB 28, 2017, View Source [SID1234517901]).

"During the fourth quarter of 2016 and beginning of this year, we made significant progress toward several important corporate objectives, and anticipate a number of additional potentially value-creating milestones over the remainder of 2017," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "We have recently initiated dosing in the first pivotal study of TRC105 in patients with angiosarcoma in both the U.S. and Europe following beneficial discussions with regulators in both regions. In addition, we intend to initiate the first-in-human clinical trial of TRC253, one of the two compounds in-licensed from Janssen last year, in patients with prostate cancer in the first half of 2017. Finally, we expect our partner, Santen, to initiate Phase 2 development of DE-122, the ophthalmic formulation of TRC105, in wet AMD later this year. Importantly, we are leveraging our unique and differentiated product development platform to complete all of our development activities, and look forward to continued progress throughout the course of the year."

Fourth Quarter 2016 and Recent Corporate Highlights

In February 2017, the Company initiated dosing in the Phase 3 TAPPAS (a randomized Phase 3 trial of TRC105 And Pazopanib versus Pazopanib alone in patients with advanced AngioSarcoma) trial of TRC105. In January 2017, the Company announced that agreement was reached with the U.S. Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) for the protocol design, clinical endpoints and statistical analysis approach for the TAPPAS trial. This one-to-one randomized trial of TRC105 in combination with Votrient (pazopanib) versus single agent Votrient features an adaptive enrichment design which allows for greater flexibility and efficiency to identify potential signs of clinical benefit.
In February 2017, the Company announced that the combination of TRC105 and Avastin did not improve median PFS versus single agent Avastin in recurrent GBM patients, although the combination was associated with a non-significant increase in overall survival. Detailed survival data and the correlative analyses are expected to be presented at an oncology conference later this year.
In January 2017, the FDA cleared the IND for TRC253, a small molecule competitive inhibitor of the wild type androgen receptor and androgen receptor mutations that confer resistance to Xtandi (enzalutamide) and other drugs approved to treat prostate cancer. TRC253 was in-licensed as part of the Company’s strategic licensing collaboration with Janssen Pharmaceutica N.V. in September 2016. TRACON expects to initiate dosing in a Phase 1/2 trial of TRC253 in the first half of 2017.
In November 2016, the Company closed an underwritten public offering of a total of 3,018,750 shares of its common stock resulting in total gross proceeds, before deducting underwriting discounts and commissions and other offering expenses, of $17.4 million.
In November 2016, updated data from the ongoing Phase 1b/2 study of TRC105 and Votrient in patients with angiosarcoma were presented at the Connective Tissue Oncology Society (CTOS) annual meeting. The presentation indicated the combination of TRC105 and Votrient continued to demonstrate encouraging signs of activity, including ongoing durable complete responses, and was well-tolerated.
In November 2016, preclinical data from two separate liver fibrosis models were presented in a poster at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting entitled, "Endoglin Antibody Reduces the NAFLD Activity Score in the STAM Model of NASH and Reduces Liver Fibrosis Following Carbon Tetrachloride Treatment." The poster also highlighted a marked reduction in cutaneous neurofibromatosis in a sarcoma patient following dosing with TRC105 and Votrient in a Phase 2 clinical trial, suggesting the potential clinical utility of an endoglin antibody for the treatment of patients with fibrosis.
Additional Expected 2017 Milestones

Initiation of dosing in the Phase 1/2 trial of TRC253 in patients with prostate cancer.
Presentation of data from expanded cohorts in the Phase 1 trial of TRC102 and Temodar (temozolomide) by the National Cancer Institute.
Completion of the Phase 1/2 PAVE study of DE-122 in patients with wet AMD by TRACON’s partner, Santen Pharmaceutical Co., Ltd. (Santen).
Initiation of dosing in Santen’s Phase 2 AVANTE study, a randomized controlled Phase 2 trial of DE-122 and Lucentis (ranibizumab) versus single agent Lucentis in patients with wet AMD.
Announcement of top-line data from the randomized Phase 2 TRAXAR trial of TRC105 in combination with Inlyta (axitinib) in patients with advanced or metastatic renal cell carcinoma.
Completion of dose escalation in the Phase 1/2 clinical trial of TRC253.
Fourth Quarter 2016 Financial Results

Cash, cash equivalents and short-term investments were $44.4 million at December 31, 2016, compared to $35.1 million and $52.2 million at September 30, 2016 and December 31, 2015, respectively.
Collaboration revenue for the fourth quarter of 2016 was $0.6 million, compared to $1.4 million for the fourth quarter of 2015.
Research and development expenses for the fourth quarter of 2016 were $4.8 million, compared to $10.6 million for the fourth quarter of 2015. The decrease in 2016 as compared to 2015 primarily resulted from decreased TRC105 drug manufacturing expenses.
General and administrative expenses for the fourth quarter of 2016 were $1.9 million, compared to $1.7 million for the fourth quarter of 2015.
The net loss for the fourth quarter of 2016 was $6.3 million, compared to a loss of $11.0 million for the fourth quarter of 2015.