On October 19, 2019 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical-stage pharmaceutical company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported that the first patient has been treated in the Phase 1 cohort of INCB01158 (also known as CB-1158) in combination with Keytruda (pembrolizumab), an anti-PD1 immune checkpoint inhibitor (Press release, Calithera Biosciences, OCT 19, 2017, View Source [SID1234535255]). INCB01158 is a potent, selective, oral inhibitor of arginase being developed pursuant to a global collaboration and license agreement with Incyte Corporation.

"Arginase is involved in the metabolism of a key amino acid that is required for optimal anti-cancer immune function," said Susan M. Molineaux, Ph.D., founder, Chief Executive Officer and President of Calithera Biosciences. "In combination with an anti-PD1 therapy, an inhibitor of arginase may reduce immunosuppression caused by myeloid cells and broaden the reach of immuno-oncology therapies."

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The Phase 1 trial (NCT02903914) is designed to evaluate the safety and recommended Phase 2 dose of INCB01158 as a monotherapy, and in combination with immune checkpoint therapy. The trial was initiated in September 2016 and is designed to enroll monotherapy expansion cohorts of patients with advanced non-small cell lung cancer, colorectal cancer and other solid tumors. The recommended Phase 2 monotherapy dose has been selected, and several cohorts of additional tumor types have been added to the trial design. Expansion cohorts of INCB01158 dosed in combination with Keytruda are expected to enroll patients diagnosed with non-small cell lung cancer, melanoma, urothelial cell carcinoma, colorectal cancer, gastroesophageal cancer, squamous cell head and neck cancer and mesothelioma

October 19, 2017 DCPrime BV, a clinical stage company developing dendritic cell vaccines to treat cancer, and apceth Biopharma GmbH, an established contract manufacturing organization in the field of gene and cell therapy, report that they have entered into a strategic manufacturing agreement (Press release, apceth, OCT 19, 2017, View Source [SID1234531599]). The collaboration involves clinical batch production and the development of a commercial scale manufacturing process of cancer vaccines based on DCPrime’s technology platform DCOne. The companies also announce that apceth has recently successfully passed an inspection by the District Government of Upper Bavaria and the Paul-Ehrlich-Institute for the manufacturing license for production of DCP-001, DCPrime’s lead program. This will enable DCPrime to enter into a Phase II Proof of Concept study in Acute Myeloid Leukemia.

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"Precisely because our platform allows, for the first time, production of dendritic cell vaccines in an off-the-shelf manner, and bypasses the costly and complicated manufacturing procedures of patient-derived dendritic cell vaccines, it is crucial for DCPrime to partner with apceth Biopharma, an experienced contract manufacturing company. This collaboration will be instrumental in bringing our innovative therapies to as many patients as possible", says Dr Ada Kruisbeek, founder and CEO & CSO of DCPrime.

"We are pleased that our manufacturing relationship with DCPrime has started in such a successful manner and that after only one year, we can already ensure production of clinical batches and product supply to patients for further development of the first off-the-shelf dendritic cell vaccine to enter Phase II clinical studies", says Dr Christine Guenther, apceth Biopharma’s CEO. "We at apceth are also very pleased that we will continue our relationship in the future, to enable large scale production and therefore product supply to even larger numbers of cancer patients".

"It has been a pleasure working with the professional staff of apceth Biopharma during the early phases of technology transfer of our current production process, and we look forward to the next steps with respect to developing a commercial scale manufacturing process", says Dr Sandra van Wetering, COO of DCPrime.

ATOR-1015 (previously designated ADC-1015) is a bispecific immune activating antibody, developed for tumor-directed immunotherapy. The drug candidate binds to two different immunomodulating target proteins: the inhibitory checkpoint receptor CTLA-4, and the co-stimulatory receptor OX40. The OX40 binding part originates from ALLIGATOR-GOLD, and the CTLA-4 binding part was generated by FIND optimization of CD86, which is a natural binder to CTLA-4.

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ATOR-1015 is capable of binding individual T-cells simultaneously, thereby bringing those cells in close proximity, which may support the immune activating effect. It reduces the number of regulatory T-cells and activates effector T-cells. A strong immune activation is expected to be achieved primarily in environments where both target molecules are expressed at high levels, such as inside a tumor. Taken together, this results in an effective immune activation as well as localization of the effect to the tumor environment, the latter being expected to minimize immune-related side effects. The objective of ATOR-1015 is to be the first CTLA-4 and OX40-binding bispecific antibody to achieve a strong anti-tumor effect, either as a monotherapy or in combination with currently established immunotherapies such as PD-1 and PD-L1 blockers. ATOR-1015 is expected to be suitable for treating a large number of different forms of cancer.

Based on the promising results from concept validation and initial preclinical studies, cell line development, aimed at subsequent large-scale production for clinical trials, was initiated in January 2016. The program is currently in the second phase of production, process development, and is planned to be ready for clinical trials during 2018.

On October 19, 2017 RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on late clinical-stage development and commercialization of proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, reported a planned poster presentation relating to the active metabolite of MESUPRON, WX-UK1, at the 2017 AACR (Free AACR Whitepaper)-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference, on Sunday, October 29, 2017, from 12:30 – 4:00 PM, at the Pennsylvania Convention Center in Philadelphia, PA (Press release, RedHill Biopharma, OCT 19, 2017, View Source [SID1234521042]).

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MESUPRON is a proprietary, first-in-class, orally-administered protease inhibitor, with several potential mechanisms of action to inhibit tumor invasion and metastasis. MESUPRON presents a new, non-cytotoxic approach to cancer therapy and potentially to additional inflammatory gastrointestinal diseases, such as diarrhea-predominant irritable bowel syndrome (IBS-D), pancreatitis and inflammatory bowel disease (IBD).

The poster1, entitled ‘New potential therapeutic applications of WX-UK1 as a specific and potent inhibitor of human trypsin-2 and human trypsin-3′, was authored by scientists from the Department of Molecular Biology and Genetics of Aarhus University in collaboration with RedHill Biopharma. The abstract presents data from non-clinical studies, concluding that WX-UK1 is a potent and rather specific inhibitor of human trypsin-2 and human trypsin-3, suggesting new potential therapeutic applications of WX-UK1 in oncology and inflammatory gastrointestinal diseases.

RedHill acquired the exclusive worldwide development and commercialization rights to MESUPRON, excluding China, Hong Kong, Taiwan and Macao, from Germany’s WILEX AG for all indications. WILEX AG completed several clinical studies with MESUPRON for different indications, including two Phase II proof-of-concept studies, one for pancreatic cancer and one for metastatic breast cancer.

RedHill has an ongoing research collaboration agreement with the Department of Molecular Biology and Genetics of Aarhus University in Denmark for the evaluation of MESUPRON. The non-clinical studies with MESUPRON are intended to support the clinical data from previous Phase I and Phase II studies, and may allow RedHill to take a precision medicine approach going forward. Further evaluation of MESUPRON, together with Aarhus University, may allow for selection of appropriate subpopulations of patients toward demonstrating the activity of MESUPRON in planned clinical trials.

About MESUPRON:
MESUPRON is a proprietary, first-in-class, orally-administered potent protease inhibitor of human trypsin-2 and human trypsin-3, targeting pancreatic cancer and inflammatory gastrointestinal diseases. Protease inhibitors have been shown to play key roles in tumor invasion and the metastasis process. High levels of certain proteases are associated with poor prognosis in various solid tumor cancers, such as pancreatic, gastric, breast and prostate cancers. MESUPRON presents a promising new non-cytotoxic approach to cancer therapy with several potential mechanisms of action to inhibit both tumor metastasis and growth. MESUPRON has undergone several Phase I studies and two Phase II proof-of-concept studies. The first Phase II study was in locally-advanced, unresectable pancreatic cancer and the second study in metastatic breast cancer in combination with first-line chemotherapeutic agents. RedHill received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for a new patent covering the use of MESUPRON and RedHill’s Phase II-stage investigational compound, YELIVA, in combination with a known antibiotic, for hard-to-treat cancers.

ATOR-1017 is an agonistic IgG4 antibody that activates the co-stimulatory receptor 4-1BB (CD137, TNFRSF9) (Company Pipeline, Alligator Bioscience, OCT 19, 2017, View Source [SID1234521032]). It was developed from Alligator´s human antibody library, ALLIGATOR-GOLD. In the development of ATOR-1017, Alligator has used their extensive expertise in the TNF receptor superfamily to develop a compound with a clear differentiation compared to other 4-1BB antibodies in development. Thus, ATOR-1017 has a unique target binding profile compared to the two 4-1BB antibodies currently in clinical development. In addition, its agonistic function is dependent on cross-linking by Fcγ receptors expressed by immune cells. The properties of the antibody directs the immune activation to the tumor area where 4-1BB as well as Fcγ receptors are highly expressed, resulting in a favorable safety-efficacy profile. ATOR-1017 therefore has the potential to be a best-in-class 4-1BB antibody in terms of risk-benefit profile.

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