On April 10, 2018 harles River Laboratories International, Inc. (NYSE: CRL) reported that its team of oncology experts is presenting 13 scientific posters, both independently and collaboratively with clients, and will highlight an enhanced oncology portfolio at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Charles River Laboratories, APR 10, 2018, View Source [SID1234525254]). The meeting is taking place from April 14-18, 2018, at McCormick Place in Chicago, Illinois.

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Throughout the meeting, Charles River’s experts will present the Company’s industry-leading oncology capabilities and highlight the latest advancements by presenting innovative applications for CRISPR/Cas9, immuno-oncology, in vitro assays, and more.

Noteworthy posters include:

Determination of signal transduction pathway activity in patient-derived xenograft models in comparison with clinical patient tumor samples for a variety of human cancer types (Presented: Monday, April 16, 8:00 a.m.-12:00 p.m.) This project, completed with Philips Molecular Pathway Diagnostics, describes an analysis method which identifies and quantifies activity in the cell signaling pathways of Charles River’s patient-derived xenograft (PDX) tumor models.
A translational platform using primary human immune cells in vitro, syngeneic and humanized models in vivo to support and advance immuno-oncology drug discovery (Presented: Monday, April 16, 8:00 a.m.-12:00 p.m.) Researchers established a translational immuno-oncology platform with the capability of progressing biologics or small-molecule modulators of immune response from in vitro and ex vivo through in vivo assays, including humanized models.
Quantitative measurement of immune-modulatory mediators within tumors of freely moving mice utilizing in vivo microdialysis (Presented: Tuesday, April 17, 8:00 a.m.-12:00 p.m.) Leveraging microdialysis in tumors, researchers monitored changes in biochemical elements within tumors to better understand cancer biology in the development of novel therapies.
A full schedule of Charles River’s activities during AACR (Free AACR Whitepaper) 2018 is available online. Reprints of each poster will be available in Booth #1615 during the conference and Charles River experts will be available for meetings to discuss how an integrated approach can support drug discovery and development programs from hit ID to IND. Throughout the conference, Charles River will be providing live updates on the Eureka Blog, including reviews of scientific sessions and input on the research being presented.

Bioinformatic Additions to Compendium

In February 2018, Charles River announced the launch of its new online Tumor Model Compendium web interface. The new Compendium interface provides oncology researchers with an easily accessible, user-friendly resource to identify tumor models based on specific molecular and histological properties, accompanied by selected patient information. Ahead of AACR (Free AACR Whitepaper), Charles River will incorporate the signal transduction pathway activity, developed with Philips Molecular Pathway Diagnostics, as a characteristic of Charles River’s PDX models. The resemblance of these pathways to clinical samples will lead to better development and clinical application of targeted drugs for personalized cancer treatment.

Select Humanization Kit

Recently, Charles River and HemaCare Corporation (OTCBB: HEMA) formed a strategic partnership to advance human immune system research by developing a more efficient and reliable method of working with humanized mice. Through the partnership, HemaCare’s peripheral blood mononuclear cells (PBMCs) are paired with Charles River’s NCG triple immunodeficient mouse. This NCG/PBMC Select Humanization Kit is the first of its kind in the industry and provides both the NCG mouse and vials of prescreened human PBMCs, allowing researchers to efficiently develop humanized mouse models on their own timeline.

Approved Quotes

"Our scientists are exploring groundbreaking applications of innovative tools and technologies across oncology research. From CRISPR to in vitro immuno-oncology to microdialysis, our deep scientific bench affords us a unique opportunity to leverage learnings from different therapeutic areas and apply them to oncology. We’re proud to showcase our body of work at AACR (Free AACR Whitepaper) this year." –Birgit Girshick, Corporate Executive Vice President, Discovery and Safety Assessment, Charles River
"The continued expansion of our Tumor Model Compendium highlights the significant role bioinformatics plays in oncology research. Scientists require data to conduct their research efficiently and effectively. Our Compendium puts the power of our data in their hands—eliminating steps and driving the development process forward." –Aidan Synnott, Executive Director, Discovery Oncology, Charles River
About the American Association for Cancer Research (AACR) (Free AACR Whitepaper)

The mission of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) is to prevent and cure cancer through research, education, communication, and collaboration. Through its programs and services, the AACR (Free AACR Whitepaper) fosters research in cancer and related biomedical science; accelerates the dissemination of new research findings among scientists and others dedicated to the conquest of cancer; promotes science education and training; and advances the understanding of cancer etiology, prevention, diagnosis, and treatment throughout the world.

On April 10, 2018 AngioDynamics, Inc. (NASDAQ: ANGO), a leading provider of innovative, minimally invasive medical devices for vascular access, peripheral vascular disease, surgery and oncology, reported that it will present at the following two investor conferences in May (Press release, AngioDynamics, APR 10, 2018, View Source [SID1234525255]):

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Conference: Deutsche Bank 43rd Annual Healthcare Conference
Location: Boston, MA
Date: Tuesday, May 8, 2018
Presentation: 3:30 p.m. ET
Speakers: Jim Clemmer, President and Chief Executive Officer, and Michael C. Greiner, Executive Vice President and Chief Financial Officer

Conference: UBS Global Healthcare Conference
Location: New York, NY
Date: Monday, May 21, 2018
Presentation: 9:00 a.m. ET
Speaker: Jim Clemmer, President and Chief Executive Officer

A live webcast of each presentation will be accessible through the "Investors" section of the Company’s website at www.angiodynamics.com and will be available for replay following each event.

On April 11, 2018 Molecular Partners AG (ticker: MOLN), a clinical-stage biopharmaceutical company developing a new class of drugs known as DARPin therapies*, reported that Molecular Partners and AstraZeneca (LON: AZN) will collaborate on Molecular Partners’ ongoing phase 1b/2 clinical study of MP0250 with osimertinib (Tagrisso) for the treatment of patients with EGFR-mutated Non-Small Cell Lung Cancer (NSCLC) pre-treated with osimertinib (Press release, Molecular Partners, APR 11, 2018, View Source [SID1234525260]). Under the collaboration, AstraZeneca will supply osimertinib (Tagrisso) required for the clinical study. The clinical study is planned to enroll approx. 40 patients and is taking place in the United States.

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"We are delighted to welcome AstraZeneca as collaboration partner for our second phase 2 study of MP0250. This underlines the growing interest in MP0250 and nicely documents the potential value of MP0250 in EGFR-mutated NSCLC," said Dr. Andreas Harstrick, Chief Medical Officer at Molecular Partners.

MP0250 offers the possibility of targeting two main tumor escape pathways by blocking both hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) simultaneously while continued treatment with osimertinib suppresses EGFR-mutated NSCLC tumor cells.

Osimertinib is a third generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitising and EGFR T790M-resistance mutations, with clinical activity against CNS metastases, which demonstrated significant benefit in untreated EGFR-mutated NSCLC patients in a global phase 3 trial last year. Osimertinib is currently marketed globally, as Tagrisso, for the treatment of locally advanced or metastatic EGFR T790M NSCLC.

The clinical study[1] consists of two parts: the dose-escalation phase (Part A), to establish a safe
recommended dose for MP0250 in combination with osimertinib. In the subsequent treatment
expansion phase (Part B), patients will be further evaluated for efficacy and safety.

[1] ClinicalTrials.gov identifier NCT03418532

About the DARPin Difference
DARPin therapeutics are a new class of protein therapeutics opening an extra dimension of multi-specificity and multi-functionality. DARPin candidates are potent, specific, safe and very versatile. They can engage in more than 5 targets at once, offering potential benefits over those offered by conventional monoclonal antibodies or other currently available protein therapeutics. The DARPin technology is a fast and cost-effective drug discovery engine, producing drug candidates with ideal properties for development and very high production yields.

With their good safety profile, low immunogenicity and long half-life in the bloodstream and the eye, DARPin therapies have the potential to advance modern medicine and significantly improve the treatment of serious diseases, including cancer and sight-threatening disorders. Molecular Partners is partnering with Allergan to advance clinical programs in ophthalmology, and is advancing a proprietary pipeline of DARPin drug candidates in oncology. The most advanced global product candidate is abicipar, a molecule currently in Phase 3, in partnership with Allergan.

Several DARPin molecules for various ophthalmic indications are also in development. The most advanced systemic DARPin molecule, MP0250, is in Phase 1 clinical development for the treatment of solid tumors and in Phase 2 development for hematological tumors. In addition, Molecular Partners intends to further evaluate MP0250 for solid tumors in a phase 1b/2 trial for EGFR-mutated NSCLC. MP0274, the second-most advanced DARPin drug candidate in oncology, has broad anti-HER activity; it inhibits HER1, HER2 and HER3-mediated downstream signaling via Her2, leading to induction of apoptosis. MP0274 has moved into Phase 1. Molecular Partners is also advancing a growing preclinical pipeline that features several immuno-oncological development programs. DARPin is a registered trademark owned by Molecular Partners AG.

On April 10, 2018 Trillium Therapeutics Inc. (Nasdaq/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported its TTI-621 and TTI-622 clinical programs (Press release, Trillium Therapeutics, APR 10, 2018, View Source [SID1234525242]). TTI-621 and TTI-622 target CD47, a protein commonly found on the surface of cancer cells. CD47 emits a "do not eat" signal to the immune system, allowing cancer cells to evade detection.

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TTI-621 Program

TTI-621 (SIRPa-IgG1 Fc) is a decoy receptor that blocks CD47 and delivers an activating signal to effector cells such as macrophages through its IgG1 Fc region. It is being evaluated in two multi-center clinical trials using intravenous or intratumoral administration and preliminary data from both studies were reported at last year’s American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Notably, weekly infusions of TTI-621 were shown to be well tolerated and intratumoral injection was observed to reduce local lesions in 9 out of 10 patients with mycosis fungoides, a common type of cutaneous T-cell lymphoma (CTCL). Building upon these monotherapy results, Trillium has refined and focused its TTI-621 clinical program.

"Our thorough signal-seeking efforts in the TTI-621 program have successfully identified T-cell lymphoma as an indication of interest," said Dr. Niclas Stiernholm, President and CEO of Trillium Therapeutics. "Consequently, we are now moving forward with a more focused TTI-621 program that reflects our commitment to vigorously pursue this signal in both the intravenous and intratumoral trials."

Recent key modifications to the intravenous dosing study (TTI-621-01, NCT02663518) include:

Focusing near-term efforts on patients with CTCL and peripheral T-cell lymphoma (PTCL). These patients are being enrolled in separate cohorts that will be evaluated using a Simon 2-stage design, with a maximum of 35 subjects in each cohort.
Introducing a standardized intra-subject dose intensification schedule for all newly enrolled subjects to increase drug exposure.
Instituting a number of phase 2-like design elements, such as an independent data monitoring committee and central review of diagnostic pathology as well as radiographic disease imaging.
Recent key changes to the intratumoral dosing study (TTI-621-02, NCT02890368) include:

Increasing the duration of treatment to allow for weekly continuation therapy.
Ability to increase the size of each cohort from 12 to 40 patients based on early signs of clinical benefit.
Establishing new cohorts to study intratumoral TTI-621 in combination with a PD-1 or PD-L1 inhibitor, pegylated interferon-alpha 2a, talimogene laherparepvec (T-vec) or radiation therapy.
TTI-622 Program

TTI-622 (SIRPa-IgG4 Fc) is the second SIRPaFc decoy receptor that Trillium is advancing into the clinic. TTI-622 consists of the same CD47-binding domain of human SIRPa as TTI-621 but linked to an IgG4 Fc region, which has a more restricted ability to engage activating Fc receptors. It is expected to have a different pharmacologic profile than TTI-621 and is being developed primarily for combination therapy. Like TTI-621, TTI-622 has the advantage of minimal binding to human red blood cells, thereby reducing the risk of anemia and a large antigen sink effect.

"TTI-622 allows us to deepen our presence in the CD47 space," added Dr. Stiernholm. "With this agent we now have two SIRPaFc decoy receptors being evaluated in clinical trials, each with a different level of Fc receptor engagement. We are excited to compare and contrast the activity of these molecules and determine if each has unique applications that could benefit cancer patients."

A two-part, multicenter, open-label, phase 1a/1b study of TTI-622 in patients with advanced relapsed or refractory lymphoma or multiple myeloma is being initiated, with the first patient expected to be dosed in Q2 2018. In the phase 1a dose-escalation part, patients will be enrolled in sequential dose cohorts to receive TTI-622 once weekly to characterize safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose. In the phase 1b part, patients will be treated with TTI-622 in combination with rituximab, a PD-1 inhibitor or a proteasome inhibitor-containing regimen

On April 10, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported that the first patient was dosed in a global Phase 2 clinical trial of tislelizumab, an investigational anti-PD-1 antibody, in patients with previously treated advanced hepatocellular carcinoma (HCC or liver cancer) (Press release, BeiGene, APR 10, 2018, View Source;p=RssLanding&cat=news&id=2341754 [SID1234525244]).

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"We have made great progress in the development of tislelizumab with three global Phase 3 trials now enrolling patients. Along with our partner, Celgene, we are encouraged by this progress and excited for the development opportunity of tislelizumab globally," commented John V. Oyler, Founder, Chief Executive Officer, and Chairman of BeiGene.

"This potentially registration-enabling trial of tislelizumab is expected to help us further understand its safety and efficacy with respect to the line of treatment in which it is administered to patients with advanced liver cancer. For these patients, as well as for patients in the concurrent front-line Phase 3 study of tislelizumab as compared to sorafenib, we are hopeful that tislelizumab will provide a new treatment option for a patient population with significant unmet needs," commented Amy Peterson, M.D., Chief Medical Officer for Immuno-Oncology of BeiGene.

The Phase 2, multi-center trial is designed to evaluate the efficacy and safety of tislelizumab in patients who were previously treated for unresectable HCC. Approximately 225 patients will be enrolled at approximately 75 cancer centers internationally including Greater China (including Taiwan), the United States, and Europe. Patients will receive a 200 mg dose every three weeks.

The trial’s primary endpoint is overall response rate (ORR) evaluated by an Independent Review Committee (IRC), and secondary endpoints include duration of response (DOR), progression-free survival (PFS), disease control rate (DCR) and clinical benefit rate (CBR) assessed by IRC, and overall survival. Additional secondary endpoints include investigator assessed ORR, DOR, PFS, DCR and CBR, safety and tolerability and health-related quality of life.

"I look forward to evaluating tislelizumab for patients with advanced liver cancer, for whom the expected median survival is typically less than one year. Patients who have either not seen benefit from their front-line or even second-line treatments, or who may have lost an initial response, could potentially respond to tislelizumab. We are excited to build upon the knowledge base we have from the dose expansion cohort of patients with HCC from its Phase 1 trial," said Professor Ann-Lii Cheng, M.D., Ph.D., Distinguished Professor and Superintendent of the Cancer Center of National Taiwan University and principal investigator of the trial.

For more information about the trial, patients and physicians should email BeiGene at [email protected].

About Hepatocellular Carcinoma

HCC is a major global health problem, accounting for 85-90 percent of all reported cases of liver cancer.i Liver cancer is the sixth most common type of cancer, with an estimated 782,000 new cases per year worldwide; it was also the second most common cause of cancer-related mortality, responsible for an estimated 746,000 deaths.ii China accounts for approximately 50 percent of both new HCC cases and HCC-related deaths worldwide.ii

About Tislelizumab

Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. It is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is potentially differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells, based on preclinical data. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia (except Japan).