On January 31, 2020 OncoArendi Therapeutics reported that funding awarded by NCBR will allow us to launch another R&D project initiating the new deubiquitinase research platform, which will expand OncoArendi’s R&D pipeline of more advanced R&D programs in the chitinase and arginase platforms (Press release, OncoArendi Therapeutics, JAN 31, 2020, View Source [SID1234553747]). The new platform comprises a group of promising biological targets in immuno-oncology allowing us to solidify our expertise in the most attractive and dynamic area of cancer treatment. The aim of the funded project is to develop a new, anti-cancer drug candidate for immunotherapy of multiple cancers. The competitive advantage of the new experimental drug over currently available therapies will be associated with its unique mechanism of action, safety and efficacy profile, especially when compared to chemotherapy and biologics. Inhibiting deubiquitinase (DUBs) is an innovative therapeutic approach, which complements and expands our expertise developed in the area of ​​arginase inhibitors. It is a natural direction for the growth and expansion of our research pipeline .

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Some deubiquitinase enzymes modulate the level of key proteins in the immune system response to cancer because they regulate the ubiquitination process and subsequent protein degradation. Ubiquitination is an essential process of protein marking for degradation in the organism necessary to activate the cellular "clean-up" system responsible for regulating cell functioning, including multiplication, dying, immune response or antigen presentation. Excessive activity of deubiquitinase can disrupt normal ubiquitination process, which causes many diseases including cancers and neurodegenerative diseases. Inhibiting deubiquitinase hyperactivity restores correct body’s immune response to cancer.

In 2019 OncoArendi carried out pilot exploratory research aimed at blocking the DUBs targets. We were able to develop and validate several new screening assays and counterscreens based on natural deubiquitinase substrates. As a result an early lead structure was identified out of two classes of compounds, which appear to both stimulate the immune response to cancer cells and directly inhibit the proliferation of cancer cells and promote apoptosis. Within the project the company will enter the early lead optimization phase.

On January 31, 2020 Sandoz reported that it has successfully completed the acquisition of the Japanese business of Aspen Global Incorporated (AGI), a wholly owned subsidiary of Aspen Pharmacare Holdings Limited. Sandoz has acquired all of the shares in Aspen Japan K.K. and associated assets held by AGI (Press release, Novartis, JAN 31, 2020, View Source [SID1234553732]).

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"The successful completion of the acquisition of Aspen’s Japanese operations promises to significantly strengthen our position in Japan, a stable and growing market." said Sandoz CEO Richard Saynor. "We are making bold moves in the marketplace to deliver on our purpose to pioneer access for patients by helping to address Japan’s patient and customer needs."

The acquisition enables Sandoz to expand its presence in Japan’s marketplace, the third largest for generics and off-patent medicines worldwide. It also strengthens Sandoz’s presence in the hospital channel by complementing the broad Sandoz portfolio and pipeline of hospital generic and biosimilar products in Japan with a dedicated sales, marketing and medical organization.

Aspen’s portfolio in Japan consists of approximately 20 products of off-patent medicines with a focus on anesthetics (including Xylocaine) and specialty brands (including Imuran) and local brands. Additionally, Sandoz has entered into a five year manufacturing and supply agreement (with an additional two year extension option) with AGI for the supply, by AGI, of active pharmaceutical ingredients, semi-finished and finished goods related to the portfolio of products acquired by Sandoz through the transaction.

On January 31, 2020 Oncotarget reported Intratumoral injection of SD-101 induces significant anti-tumor immunity in preclinical and clinical studies, especially when combined with PD-1 blockade (Press release, Oncotarget, JAN 31, 2020, View Source [SID1234553748]).

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Combination therapy generated CD8+ T cell dependent immunity leading to rejection of both non-injected and injected tumors and long-term survival, even in very large tumors.

Dr. Mary J. Janatpour from Dynavax Technologies, Inc., Emeryville, CA 94608,USA said, "It has long been appreciated by cancer researchers that the phenotypic heterogeneity and progressive evolution of malignant tumors minimizes the chance that any agent targeting a single molecular pathway could effectively cure advanced cancer."

The authors have previously demonstrated in mouse tumor models that employing the innate immune system to prime a T cell response, in combination with checkpoint blockade, results in deep and durable anti-tumor efficacy.

These high response rates were observed in both injected and non-injected tumor lesions and patients with PD-L1 negative tumors, indicating low levels of basal immune inflammation, responded as well as patients with PD-L1 positive tumors.

Intratumorally administered SD-101 exerts its priming activity and ultimate orchestration of a systemic anti-tumor T cell response through multiple mechanisms.

The production of interferon stimulates tumor cell killing by natural killer cells, with ensuing tumor antigen release, and induces chemokines that attract T cells back to the tumor bed.

Low-dose cyclophosphamide decreases Tregs. Additional impacted biological activities have been described, such as:

increased interferon production,
induction of immunogenic cell death,
increases in effector T cells, and
increases in functional NK cells,
…likely to be complementary to SD-101 activity by virtue of modulation of the TME. By administering SD-101 locally, rather than systemically, the researchers demonstrate that localized SD-101 injection combined with systemically administered low-dose cyclophosphamide confers an anti-tumor response at non-injected sites.

The Janatpour research Team concluded that, taken together, the intratumoral SD-101 plus low-dose CY combination may complement existing checkpoint blockade therapies in patients to improve efficacy in the clinic and extend the benefits of immunotherapy to more patients.

On January 30, 2020 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) announced today that its partner Bayer AG has decided to advance a further programme from the endometriosis multi-target alliance into clinical Phase I development (Press release, Evotec, JAN 30, 2020, View Source;announcements/press-releases/p/evotec-and-bayer-advance-further-programme-into-phase-i-clinical-development-5905 [SID1234553682]). Evotec will receive a milestone payment of € 2 m upon first dosing in the Phase I clinical trial and may be eligible for further significant clinical and sales milestones as well as royalties depending on the future progress during clinical development and potential commercialisation of a drug in the future.

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The companies entered into their endometriosis multi-target discovery alliance in October 2012 with the aim to discover three clinical candidates. So far, the alliance generated six pre-clinical candidates, of which a fourth has now progressed into Phase I. Bayer advanced the first programme into a Phase II trial in refractory chronic cough in 2018. The Phase II study yielded positive results which met all of the targeted endpoints. For more information about this Bayer/Evotec alliance also see "White Paper on Bayer/Evotec Alliance".

Dr Werner Lanthaler, Chief Executive Officer of Evotec, commented: "We are very pleased that the excellent collaboration between Bayer and Evotec has now officially surpassed the ambitious initial target by delivering a fourth clinical drug candidate. The candidates we have identified and developed together are performing extremely well and hold great potential, most likely also beyond the initially surveyed indications."

On January 30, 2020 GlycoMimetics, Inc. (Nasdaq: GLYC) reported that Duke University investigators have dosed the first patient in a proof-of-concept Phase 1b study to evaluate GlycoMimetics’ novel GMI-1359 drug candidate in patients with advanced breast cancer (Press release, GlycoMimetics, JAN 30, 2020, View Source [SID1234553700]). The dose-escalating study will enroll up to 12 individuals with metastatic, hormone receptor positive breast cancer with stable or minimally progressive disease, including bone metastasis. GMI-1359 is a dual inhibitor of both E-selectin and CXCR4. The trial is designed to evaluate safety, pharmacokinetics and pharmacodynamic measures of biologic activity, such as increases in circulating tumor cells and mobilization of CD34+ and immune T-cell subsets. GlycoMimetics expects the trial results to be available in late 2020, the conclusions of which the Company will use to inform future development of GMI-1359.

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Kelly Marcom, M.D., and Dorothy Sipkins, M.D., Ph.D., both of the Duke Cancer Institute, are the trial’s co-principal investigators.This clinical trial builds on published findings from Dr. Sipkins on the key roles of both E-selectin and CXCR4 in the trafficking of metastatic cancer cells and of their establishment as micro-metastases in bone. Dr. Sipkins’ research suggests that both E-selectin and CXCR4 mediate key mechanisms that promote progression and migration of cancer cells to protective niches in the bone marrow micro-environment, and reveals the potential for an E-selectin and CXCR4 inhibitor like GMI-1359 to molecularly excise disseminated breast cancer cells.1

"The initiation of enrollment is an important milestone in our exploration of GMI-1359 and its potential as a novel approach to treating metastatic cancer," said GlycoMimetics Senior Vice President of Clinical Development and Chief Medical Officer Helen Thackray, M.D., FAAP. "We’re pleased to have such distinguished researchers at Duke University begin to explore the use of this investigational therapy and look forward to learning more about its potential impact as clinical study advances."

More information on this clinical trial can be found at www.clinicaltrials.gov.

About GMI-1359

GMI-1359 is designed to simultaneously inhibit both E-selectin and CXCR4. E-selectin and CXCR4 are both adhesion molecules involved in tumor trafficking and metastatic spread. Preclinical studies indicate that targeting both E-selectin and CXCR4 with a single compound could improve efficacy in the treatment of cancers that involve the bone marrow such as acute myeloid leukemia and multiple myeloma or in solid tumors that metastasize to the bone, such as prostate cancer and breast cancer, as well as in osteosarcoma, a rare pediatric tumor. GMI-1359 has completed a Phase 1 clinical trial in healthy volunteers. The newly initiated Phase 1b clinical study in breast cancer patients is designed to enable investigators to identify an effective dose of the drug candidate and to generate initial biomarker data around the drug’s activity.