On April 16, 2016 Redx Pharma’s cancer subsidiary, Redx Oncology, reported that it has developed novel, differentiated, reversible small molecule inhibitors of Bruton’s tyrosine kinase (BTK) and will be presenting its poster to the scientific community next week at the AACR (Free AACR Whitepaper)’s 2016 annual gathering (Press release, Redx Pharma, APR 16, 2016, View Source [SID1234524743]). Redx’s lead compound has a favorable in vitro safety profile and drug-like properties, displaying an improved CYP profile to competitor compounds. In vivo PK demonstrated good oral bioavailability.

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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

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This breakthrough is part of Redx’s work to develop best-in-class treatments for leukaemia, other blood cancers, and autoimmune diseases such as rheumatoid arthritis, lupus, and Sjögren’s Syndrome.

Dr Nicolas Guisot will be presenting the program on Wednesday 20 April between 7:30 and 11:00am in Section 19, Poster Board Number 20. If you would like to meet with our scientists or business development team please contact Dr Matilda Bingham, Executive Director of Redx Oncology.

The presentation abstract and author information is available here:
View Source

Bioorthogonal turn-on probes have been widely utilized in visualizing various biological processes. Most of the currently available bioorthogonal turn-on probes are blue or green emissive fluorophores with azide or tetrazine as functional groups. Herein, we present an alternative strategy of designing bioorthogonal turn-on probes based on red-emissive fluorogens with aggregation-induced emission characteristics (AIEgens). The probe is water soluble and non-fluorescent due to the dissipation of energy through free molecular motion of the AIEgen, but the fluorescence is immediately turned on upon click reaction with azide-functionalized glycans on cancer cell surface. The fluorescence turn-on is ascribed to the restriction of molecular motion of AIEgen, which populates the radiative decay channel. Moreover, the AIEgen can generate reactive oxygen species (ROS) upon visible light (λ=400-700 nm) irradiation, demonstrating its dual role as an imaging and phototherapeutic agent.
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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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

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Aberrant epigenetic events contribute to tumorigenesis of all human cancers. Significant efforts are underway in developing new generation of epigenetic cancer therapeutics. Although clinical trials for agents targeting DNA hypermethylation and histone deacetylation have yielded promising results, developing agents that target histone methylation remains to be in the early stage. We and others have previously reported that 3-Deazaneplanocin A (DZNep) is a histone methylation inhibitor that has a wide range of anticancer effects in various human cancers. Here, focusing on acute myeloid leukemia (AML) as a model, we reported a less toxic analog of DZNep, named D9, which is shown to be efficacious in AML cell lines and patient-derived samples in vitro, as well as AML tumorigenesis in vivo. Gene expression analysis in a panel of AML cell lines treated with D9 identified a set of genes that is associated with D9 sensitivity and implicated in multiple oncogenic signaling pathways. Moreover, we show that D9 is able to deplete the leukemia stem cells (LSC) and abolish chemotherapy-induced LSC enrichment, leading to dramatic elimination of AML cell survival. Thus, D9 appears to be a robust epigenetic compound that may constitute a potential for AML therapy.

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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

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THIOMAB drug conjugates (TDCs) with engineered cysteine residues allow site-specific drug conjugation and defined Drug-to-Antibody Ratios (DAR). In order to help elucidate the impact of drug-loading, conjugation site, and subsequent deconjugation on pharmacokinetics and efficacy, we have developed an integrated mathematical model to mechanistically characterize pharmacokinetic behavior and preclinical efficacy of MMAE conjugated TDCs with different DARs. General applicability of the model structure was evaluated with two different TDCs.
Pharmacokinetics studies were conducted for unconjugated antibody and purified TDCs with DAR-1, 2 and 4 for trastuzumab TDC and Anti-STEAP1 TDC in mice. Total antibody concentrations and individual DAR fractions were measured. Efficacy studies were performed in tumor-bearing mice.
An integrated model consisting of distinct DAR species (DAR0-4), each described by a two-compartment model was able to capture the experimental data well. Time series measurements of each Individual DAR species allowed for the incorporation of site-specific drug loss through deconjugation and the results suggest a higher deconjugation rate from heavy chain site HC-A114C than the light chain site LC-V205C. Total antibody concentrations showed multi-exponential decline, with a higher clearance associated with higher DAR species. The experimentally observed effects of TDC on tumor growth kinetics were successfully described by linking pharmacokinetic profiles to DAR-dependent killing of tumor cells.
Results from the integrated model evaluated with two different TDCs highlight the impact of DAR and site of conjugation on pharmacokinetics and efficacy. The model can be used to guide future drug optimization and in-vivo studies.

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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

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On April 15, 2016 Incyte Corporation (Nasdaq: INCY) reported that it will highlight the productivity of its drug discovery and development organization and aspects of its development portfolio at an investor event on Sunday, April 17, 2016 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans, Louisiana (Press release, Incyte, APR 15, 2016, View Source;p=RssLanding&cat=news&id=2157635 [SID:1234510922]).

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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

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The event will include a discussion of Incyte’s second-generation PI3Kδ inhibitor, INCB50465; the Company’s immuno-oncology portfolio, including its anti-GITR antibody, INCAGN1876, anti-OX40 antibody, INCAGN1949, and emerging data with its small molecule BRD inhibitor, INCB54329; as well as its targeted epigenetic therapies, including a novel LSD1 inhibitor entering Phase 1 development, INCB59872 .

"Incyte operates with the conviction that investment in basic research can translate into innovative therapies that can address important unmet medical needs. To that end, we are pleased to be able to highlight such a broad collection of abstracts from our emerging development portfolio at this year’s AACR (Free AACR Whitepaper) Annual Meeting," stated Reid Huber, Ph.D., Incyte’s Chief Scientific Officer. "The research team’s productivity is a result of the quality of our scientific organization and the efficiency of our R&D model."

As part of its succession plan, Incyte also announced that after almost 13 years at the Company, Dr. Richard Levy, Chief Drug Development Officer, is retiring effective April 30, 2016. Dr. Steven Stein, Incyte’s Chief Medical Officer, will now assume all of Dr. Levy’s responsibilities. Dr. Levy was instrumental in building the broad and diverse portfolio Incyte has today, and developing Jakafi (ruxolitinib), the Company’s proprietary JAK 1/JAK 2 inhibitor