Author: [email protected]

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]).

Schedule your 30 min Free 1stOncology Demo!
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

                  Schedule Your 30 min Free Demo!

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]).

Schedule your 30 min Free 1stOncology Demo!
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

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
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

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
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

                  Schedule Your 30 min Free Demo!

"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").

https://finance.yahoo.com/news/panther-biotechnology-receives-positive-feedback-110000254.html

On December 7, 2016 Panther Biotechnology, Inc. reported that it has received positive feedback from the submission presented to the U.S. Food and Drug Administration ("FDA") pursuant to a Pre-IND (Investigational New Drug) meeting with the Division of Oncology Products 1 (DOP1) of the Center for Drug Evaluation and Research (CDER) of the FDA (Press release, Panther Biotechnology, DEC 7, 2016, View Source [SID1234517402]). The purpose of the requested meeting was to obtain FDA’s input regarding Panther’s plans for the development of TRF-DOX, Panther’s novel transferrin-doxorubicin conjugate initially planned for the treatment of platinum-resistant ovarian cancer. In preparation for the meeting, Panther submitted a Pre-IND Package to FDA that described the information Panther intends on submitting in the TRF-DOX IND submission planned in 2017. The IND is the regulatory vehicle that will allow for the initiation of clinical trials with TRF-DOX initially for the treatment of ovarian cancer.

Schedule your 30 min Free 1stOncology Demo!
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

                  Schedule Your 30 min Free Demo!

Panther submitted the request to seek guidance on a Phase 2a Open Label Sequential Cohort, Ascending Dose, Blinded, DOXIL controlled Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of Multiple Doses of TRF-DOX Administered Intravenously every 4 weeks for up to 12 months to patients with Advanced Platinum-refractory or -resistant Ovarian Cancer. The primary objective will be to evaluate the safety and tolerability of TRF-DOX administered intravenously to subjects with advanced platinum-refractory or resistant ovarian cancer for up to 12 months. Secondary objectives are tumor response rate (complete and partial responses) assessed every 3 months for 12 months following treatment according to Response Evaluation Criteria in Solid Tumors version 1.1. (RESIST) criteria, progression-free survival at 6 and 12 months following first injection of TRF-DOX and overall survival at 6 and 12 months following first injection of TRF-DOX.

FDA reviewed Panther’s manufacturing, preclinical pharmacology and toxicology, and clinical plans for TRF-DOX and provided specific feedback. In general, FDA agreed with Panther’s plans and offered further recommendations and comments. The manufacturing and nonclinical pharmacology and toxicology plans with TRF-DOX were deemed adequate pending review of actual data by FDA in the IND.

In addition, FDA had input into the design of the Phase 2b clinical trial with TRF-DOX which will be considered in the protocol submitted with the IND.

"This is a significant leap for Panther as we prepare to enter clinical trials in the US and we look forward to getting started," stated Evan Levine, Chief Executive Officer of Panther. "We are extremely pleased and thankful for not only the valuable feedback we received from FDA but also from the productive recommendations to manage TRF-DOX through the next stage of clinical development. Based on earlier encouraging clinical results, we believe we may have a greater opportunity for increasing clinical benefit for patients receiving treatment."
TRF-DOX binds to transferrin receptors on tumor cells, inhibits cancer cell proliferation and causes cell death. TRF-DOX has been shown to exhibit increased cytotoxicity relative to unconjugated doxorubicin toward a variety of cancer cell lines and reduced cytotoxicity to normal cells. In addition to improvements in cytotoxicity and selectivity, TRF-DOX exhibits cytotoxic effects in many multidrug-resistant cells in vitro. Tumor targeting of doxorubicin to transferrin receptors on the cell membranes of tumor cells is intended to improve the therapeutic index of doxorubicin and to reduce the development of doxorubicin resistance.