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Compugen Announces Key Highlights from R&D Day

On December 7, 2016 Compugen Ltd. (NASDAQ: CGEN), a leading predictive drug discovery company, reported the following key highlights from its R&D Day that took place this morning in NYC:

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Disclosure of a therapeutic antibody program targeting TIGIT to complement the Company’s CGEN-15029 program, following new data recently generated for the CGEN-15029/PVRIG program. TIGIT and PVRIG represent two distinct arms of the same biological pathway. Based on this and experimental data, the Company believes there is significant added value to developing both arms as a potential combination therapy. Compugen expects to select the lead antibody for CGEN-15137/TIGIT by end of Q1 2017.

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COM701, clinical candidate antibody targeting CGEN-15029/PVRIG, is currently undergoing process development as part of the manufacturing activities to generate clinical material. IND-filing for COM701 is anticipated in Q4 2017.

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Update on status of cancer immunotherapy partnership with Bayer entered in August 2013. As previously disclosed, after achieving all preclinical stage milestones for CGEN-15001T immune checkpoint, this program was transferred to Bayer for further development. To date, preclinical activities are on track, and pivotal toxicity studies and GMP clinical trial material production are ongoing. As previously disclosed, the second program under the partnership, CGEN-15022, is at an earlier stage and further characterization studies of its role in anti-cancer immune responses are ongoing.

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Disclosure of a new therapeutic program focusing on a protein target expressed in various cancers, and which is highly correlated with an M2 macrophages marker. The target was also shown to inhibit T cell activation in cell-based studies. Macrophages are immune cells that are highly immune suppressive in the tumor microenvironment, and targeting such cells offers the potential for efficacy in patients non-responsive to checkpoint inhibitors. Therapeutic antibody discovery activities have been initiated for this program.

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Overview of the Company’s immuno-oncology target validation pipeline activities, which primarily focus on myeloid targets. With an aim to complement and expand the patient population responsive to checkpoints inhibitors, blocking myeloid targets may serve as the next wave of cancer immunotherapies. Myeloid CGEN-target candidates have been identified within the tumor microenvironment of multiple cancers and are aggressively pursued by the Company and in collaboration with Prof. Drew Pardoll.

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The event also featured a presentation by Prof. Drew Pardoll, Chairman of Compugen’s Scientific Advisory Board and Abeloff Professor of Oncology, Medicine, Pathology and Molecular Biology and Genetics at Johns Hopkins University of Medicine, and Director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Sidney Kimmel Cancer Center, Johns Hopkins. The presentation included an overview of the immune checkpoint inhibition landscape, including both T cells and myeloid cells. Prof. Pardoll further presented in vitro and in vivo data demonstrating the importance of PVRIG/CGEN-15029 as a significant T cell immune checkpoint as well as evidences that PVRIG-blockage synergizes with PD1/PDL1 in unleashing T cell activity.

Cancer Research Technology Pioneer Fund announces investment in blood cancer drugs

On December 8, 2016 The Cancer Research Technology (CRT) Pioneer Fund reported an investment to develop a promising new class of drugs for blood cancer (Press release, Cancer Research Technology, AUG 8, 2016, View Source [SID1234523175]).

The funding will support Cancer Research UK-funded scientists at The Institute of Cancer Research, London, who are designing the drugs, to treat patients with Diffuse Large B-Cell Lymphoma – a sub-type of Non-Hodgkin Lymphoma.

The CRT Pioneer Fund was launched in 2012 by CRT, the commercialisation arm of Cancer Research UK, and the European Investment Fund (EIF) in 2012 to bridge the funding gap between cancer drug discovery and early drug development. It is managed by Sixth Element Capital LLP and has received additional investment from investment company BACIT Limited.

The drugs will target a protein called B-Cell Lymphoma 6 (BCL6). It plays an important role in maintaining levels of antibody-secreting B-cells in the blood, and is an essential part of the body’s immune defences. Research shows that BCL6 is overactive in patients with Diffuse Large B-Cell Lymphoma and that this helps drive cancer growth. This suggests that drugs designed to inhibit BCL6 could help to treat the disease.

Ian Miscampbell, managing partner of Sixth Element Capital LLP, said: "We’re delighted to announce the CRT Pioneer Fund’s investment in the BCL6 project and to be collaborating with the Institute of Cancer Research and their world class team once again. This investment will pave the way for potential new cancer drugs to be developed and taken into phase I clinical trials."

Non-Hodgkin Lymphoma affects around 13,400 people in the UK each year and around 4,800 people die from it. Diffuse Large B-Cell Lymphoma is the most common type of Non-Hodgkin Lymphoma, accounting for about 40 per cent of cases.

Professor Paul Workman, chief executive of The Institute of Cancer Research, London, said: "Diffuse Large B-Cell Lymphoma is a fast-growing and all-too-often deadly cancer. Current therapies for the disease have serious side effects and many patients relapse. We need innovative new ways of treating the disease to give patients their best chance of overcoming it.

"The support from the CRT Pioneer Fund will help us to make progress with this challenging project, with the aim of designing a whole new class of potential cancer drugs that target BCL6 – a protein that is crucial for the cancer’s rapid progression."

Dr Phil L’Huillier, Cancer Research Technology’s director of business development, said: "We’re delighted that the CRT Pioneer Fund is providing key investment exactly where it’s needed, to help accelerate this potential new treatment through to early clinical trials, so it can start to benefit patients as quickly as possible. This announcement marks the ninth investment made by the CPF, providing potential new options for patients that might otherwise never have made it beyond the lab."

Eutilex gains $18.9M in Series A round, boosting I/O trial funds

South Korean biotech Eutilex has seen a $21 billion KRW ($18.9 million) Series A funding boost as it looks to take its lead cancer med into midstage testing (Article, FierceBiotech, DEC 8, 2016, View Source [SID1234522127]).

New Breast Cancer Research Highlights BGB324 In Overcoming Immunotherapy Resistance

On December 8, 2016 Leading oncology biopharmaceutical company BerGenBio AS, reported important new preclinical study data on its first-in-class AXL inhibitor, BGB324 in another major disease indication (Press release, BerGenBio, DEC 8, 2016, View Source [SID1234517008]). The study in breast cancer showed that AXL, a key factor in tumor resistance to the emerging class of new immune checkpoint inhibitors is effectively targeted through combination therapy with BGB324. The study data was presented in a poster today at the San Antonio Breast Cancer Symposium 2016.

BGB324 is a highly selective small molecule inhibitor of the AXL receptor tyrosine kinase that is associated with poor overall survival in breast cancer. The new study "BGB324, a selective small molecule inhibitor of AXL tyrosine kinase, enhances immune checkpoint inhibitor efficacy in mammary adenocarcinoma" presented today in the Immunology and Preclinical Immunotherapy poster session, described a unique role for AXL in suppressing the anti-tumor immune response in breast cancer. AXL-targeting with BGB324 enhanced the effect of immune checkpoint blockade in aggressive mammary adenocarcinomas that display limited immunogenicity. The results showed that AXL-associated EMT and expression of immune suppressive cytokines increased in 4T1 tumors in response to immune therapy and correlated with a lack of response. The combination of BGB324 + anti-CTLA-4/anti-PD-1 resulted in durable primary tumor clearance and sustained tumor immunity in animals that rejected 4T1 tumor cell re-challenge. Importantly, the extensive metastasis to the lung, liver and spleen characteristic of this breast cancer model were concomitantly abrogated in the animals responding to the combination treatment. BGB324 enhanced tumor infiltration of effector cytotoxic T lymphocytes and NK cells while decreasing immune suppressive cell types. Notably, BGB324 showed direct effects on human M2 macrophages, reducing secretion of immune suppressive cytokines. Hence, selective inhibition of AXL signaling with BGB324 uniquely targets both tumor intrinsic and microenvironmental immune suppression mechanisms and increases checkpoint inhibitor efficacy.

Richard Godfrey, Chief Executive Officer of BerGenBio, commented:
"We believe this strong new preclinical data again clearly demonstrates the rationale for combining BGB324 with immune checkpoint inhibitors to treat a wide range of aggressive cancers. AXL expression is increased in tumors in response to checkpoint inhibitor treatment and is an important resistance mechanism. Treatment with BGB324 counters this and promotes the anti-tumor immune response. This supports our intention to combine the clinical-stage selective Axl inhibitor BGB324 with immune checkpoint inhibitors to improve treatment of human breast cancer."

About BGB324
BGB324 is a first-in-class, highly selective small molecule inhibitor of the Axl receptor tyrosine kinase. It blocks the epithelial-mesenchymal transition (EMT), which is a key driver in immune evasion, drug-resistance and metastasis. Phase Ib clinical trials are underway as single agent and in combination with standard of care drugs cytarabine in acute myeloid leukaemia (AML) and erlotinib in non-small cell lung cancer (NSCLC).

Lilly Presents neoMONARCH Phase 2 Data on Abemaciclib in Early-Stage Breast Cancer

On December 8, 2016 Eli Lilly and Company (NYSE: LLY) reported that the neoMONARCH study of abemaciclib, a cyclin-dependent kinase (CDK) 4 and CDK 6 inhibitor, met its primary endpoint of reducing expression of Ki67, a biomarker of cell proliferation, after two weeks of treatment (Press release, Eli Lilly, DEC 8, 2016, View Source [SID1234516998]). Final data from the Phase 2 trial presented during the official press program at the 2016 San Antonio Breast Cancer Symposium (SABCS) evaluated abemaciclib, both alone or in combination with the non-steroidal aromatase-inhibitor anastrozole, in postmenopausal women with previously untreated early stage hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer.

"Lilly is committed to the scientific discovery and development of new therapies that change current standards of cancer care," said Sue Mahony, Ph.D., senior vice president and president, Lilly Oncology. "The neoMONARCH data are encouraging and continue to inform our understanding of how abemaciclib could be used as both a single-agent therapy or in combination with aromatase inhibitors, such as anastrozole, in the early-stage setting."

The Phase 2 neoMONARCH trial was a randomized, multi-center, open-label study that enrolled 225 patients who had at least one measurable tumor ≥1 cm, adequate organ function, and an ECOG performance status of ≤1. Patients were randomized to one of three trial arms: 1) twice-daily abemaciclib monotherapy (150mg) for two weeks; 2) twice-daily abemaciclib (150mg) along with once-daily anastrozole (1mg) for two weeks; or 3) once-daily anastrozole monotherapy (1mg) for two weeks. All patients received an initial biopsy prior to randomization to assess baseline Ki67 expression. After the initial two-week treatment period, patients underwent a second tumor biopsy and Ki67 was assessed again.

The primary objective of the study was to assess Ki67 percentage change in the breast tumor after two weeks of therapy from the baseline measurement. The results showed that abemaciclib monotherapy and abemaciclib in combination with anastrozole significantly reduced Ki67 more than anastrozole alone. Following the initial two weeks of randomized treatment, all patients then went on to receive twice-daily abemaciclib (150mg) plus anastrozole (1mg) for a further 14 to 22 weeks.

The study protocol also included the prophylactic use of loperamide (2mg) administered twice-daily, in combination with abemaciclib for the first 28 days. No new safety signals were observed for abemaciclib when administered in combination with anastrozole.

Breast cancer is the most common cancer among American women, besides skin cancers, and is the second leading cause of cancer death among women.1 An estimated 61,000 cases of early-stage breast cancer will be diagnosed in the U.S. this year and one in eight women, or 12 percent, of women in the U.S. will develop invasive breast cancer during their lifetime.1

About Abemaciclib
Abemaciclib (LY2835219) is an investigational, oral cell cycle inhibitor, designed to block the growth of cancer cells by specifically inhibiting cyclin-dependent kinases, CDK 4 and CDK 6. In many cancers, uncontrolled cell growth arises from a loss of cell cycle regulation due to increased signaling from CDK 4 and CDK 6. Abemaciclib inhibits both CDK 4 and CDK 6, and was shown in cell-free enzymatic assays to be most active against Cyclin D 1 and CDK 4.

In 2015, the U.S. Food and Drug Administration granted abemaciclib Breakthrough Therapy Designation based on data from the breast cancer cohort expansion of the company’s Phase 1 trial, JPBA, which studied the efficacy and safety of abemaciclib in women with advanced or metastatic breast cancer. In addition to its current MONARCH clinical trials evaluating abemaciclib in breast cancer, a Phase 3 trial of abemaciclib in lung cancer is also underway.

For more information on additional abemaciclib trials, a complete listing can be found on ClinicalTrials.gov (in the search box on the home page, type in "abemaciclib").