On December 14, 2015 Corcept Therapeutics Incorporated (NASDAQ: CORT), a pharmaceutical company engaged in the discovery, development and commercialization of drugs that treat severe metabolic, oncologic and psychiatric disorders by modulating activity at the glucocorticoid receptor (GR), reported initial efficacy data from its Phase 1/2 trial of mifepristone in combination with the chemotherapy drug eribulin to treat patients with GR-positive, metastatic, triple-negative breast cancer (TNBC) (Press release, Corcept Therapeutics, DEC 14, 2015, http://www.corcept.com/news_events/view/pr_1450104306 [SID:1234508565]). The data were presented at the 2015 San Antonio Breast Cancer Symposium (SABCS) on Saturday, December 12th, 2015.

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Trial Design and Objective

Corcept is investigating whether the addition of mifepristone, the active ingredient in Corcept’s approved medication, Korlym, will enhance the effect of eribulin in patients whose TNBC tumors express GR, one of the receptors to which Korlym binds.

The trial is being conducted in two parts. In the first phase, researchers determined the maximum tolerated combined dose of mifepristone and eribulin. This dose — 300 mg of mifepristone daily with 1.1 mg/m2 of eribulin taken on days one and eight of a three week cycle — is now being administered to patients in the trial’s second, efficacy phase, which will enroll 20 patients with GR-positive, metastatic TNBC. This phase of the trial is ongoing.

Initial Efficacy Results

At SABCS, the trial’s investigators presented efficacy data from the 15 patients enrolled to-date with GR-positive TNBC who have been treated with the recommended dose (two patients from the trial’s first phase and 13 from its second). As determined using the Response Evaluation Criteria in Solid Tumors (RECIST), initial efficacy results in this group were as follows: one patient exhibited a partial response (defined as a 30 percent or greater reduction in tumor size), seven had stable disease and five had progressive disease. Two patients were too early in their treatment to be assessed.

The combination of mifepristone and eribulin has been well-tolerated. Most adverse events have been disease-related and of mild or moderate severity, with the most common being neutropenia, fatigue, hypokalemia, nausea, hair loss and neuropathy. Neutropenia has been manageable with the administration of growth factor. No patient has suffered a serious adverse event. Pharmacokinetic data show no interaction between eribulin and mifepristone.

"We are pleased that the combination of mifepristone and eribulin appears to be active in these very ill patients," said Robert S. Fishman, MD, Corcept’s Chief Medical Officer. "Our oncology program is based on the hypothesis that GR modulators such as mifepristone can enhance the efficacy of a variety of chemotherapeutic agents in GR-positive disease. We very much look forward to completing the trial. If the final results are sufficiently positive, we plan to initiate a Phase 3 trial of this treatment regimen next year."

Corcept’s trial builds on pre-clinical and clinical research performed by investigators at Corcept and at the University of Chicago showing that modulation of activity at GR enhances the effect of chemotherapy in the treatment of TNBC. At the 2013 SABC, University of Chicago researchers presented positive results of a trial in which six patients with metastatic, GR-positive TNBC received a combination of nab-paclitaxel and mifepristone

About Triple-Negative Breast Cancer

TNBC is a form of breast cancer in which the three receptors that fuel most breast cancer growth — estrogen, progesterone and HER-2 — are not present. Because the tumor cells lack these receptors, treatments that target estrogen, progesterone and HER-2 are ineffective. Approximately 40,000 women are diagnosed with triple-negative breast cancer each year. It is estimated that more than 75 percent of these women’s tumor cells express GR. There is no FDA-approved treatment and neither a targeted treatment nor an approved standard chemotherapy regimen for relapsed triple-negative breast cancer patients exists.

Corcept has licensed patents from the University of Chicago covering the use of GR antagonists in combination with chemotherapy to treat TNBC and castration-resistant prostate cancer.

About Korlym (mifepristone)

Korlym modulates the effects of excess cortisol in patients with Cushing’s syndrome. Since 2012, Corcept has marketed Korlym as a once-daily oral treatment of hyperglycemia secondary to endogenous Cushing’s syndrome in adult patients with glucose intolerance or diabetes mellitus type 2 who have failed surgery or are not candidates for surgery. Korlym was the first FDA-approved treatment for that illness, and the FDA has designated Korlym as an Orphan Drug for that indication.

On December 14, 2015 Bird Rock Bio, Inc., a clinical stage biopharmaceutical company, reported its corporate name change from RuiYi, Inc. to Bird Rock Bio (Press release, Bird Rock Bio, DEC 14, 2015, View Source [SID1234515802]).

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"With the advancement of gerilimzumab into Phase 2 for rheumatoid arthritis (RA) and RYI-018 into Phase 1 for non-alcoholic fibrotic liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) in 2016, our organization has shifted dramatically from discovery operations in Shanghai to global clinical development for novel antibody therapeutics targeting large unmet medical needs," said Paul Grayson, CEO. "We anticipate an exciting year of milestones for both of our highly differentiated antibodies and the new name reflects the shift and progress."

Backed by leading biotechnology venture investors, Bird Rock Bio’s strategy leverages biologic targets with substantial human proof of mechanism for the development of best in class molecules with strong clinical and commercial differentiation. RYI-018 is a first in class inverse agonist antibody to the CB1 receptor with anticipated clinical differentiation associated with an enhanced safety profile and gerilimzumab is a novel anti-IL-6 antibody with potential commercial differentiation as a disruptive, cost effective treatment.

Previous small molecule inverse agonists to the CB1 receptor demonstrated significant benefits in inflammation, metabolism and fibrosis (the principle contributors to NAFLD and NASH), however, these small molecule drugs had potential risk of severe CNS side effects. RYI-018 is the only known CB1 inverse agonist antibody and has demonstrated, pre-clinically, distribution to all peripheral tissues without penetration of the brain. As such, RYI-018 possesses differentiated and potentially compelling product potential for large unserved markets such as NASH. The Company is advancing RYI-018 through IND enablement and anticipates Phase 1 to initiate 2H 2016.

Gerilimzumab is a novel monoclonal antibody that is directed against the IL-6 cytokine, for the treatment of autoimmune disorders, including RA. Gerilimzumab has an ideal product profile, demonstrating in preclinical studies to have the highest known potency amongst the anti-IL-6 cytokine class and in a Phase 1 clinical trial in healthy volunteers to have an extended blood half-life, which is anticipated to support small volume dosing Bird Rock Bio once every eight weeks. This would enable high patient convenience and lowest pricing, which are compelling product features for a chronic therapy to increasingly cost-sensitive healthcare systems globally.

Bird Rock Bio believes gerilimzumab has the potential to effectively compete in the $35 billion global biologic market for rheumatoid arthritis by not only treating the large number of anti-TNF refractory patients but also becoming a front line treatment for moderate and severe patients. The Company expects to submit for its Phase 2 clinical trial in Brazil, a country with more than 1 million biologic naïve RA patients in 1H 2016

On December 14, 2015 Ignyta, Inc. (Nasdaq: RXDX), a precision oncology biotechnology company, reported that its San Diego diagnostic laboratory has been accredited by the College of American Pathologists (CAP) based on results of a recent on-site inspection (Press release, Ignyta, DEC 14, 2015, View Source [SID:1234508568]). This accreditation is awarded to facilities that meet the highest standards of quality in clinical laboratory services. With this recognition, Ignyta’s diagnostic laboratory joins the ranks of some of the most prominent clinical laboratories in the world.

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"We are extremely proud that our in-house diagnostic laboratory has achieved CAP accreditation, further validating our commitment to provide the highest quality laboratory services as part of our focus on helping healthcare providers take better care of patients suffering from cancer," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "This milestone is consistent with our vision of becoming the world’s leading precision medicine company, with an integrated approach to ‘Rx/Dx’ in oncology. Furthermore, we believe our diagnostic laboratory provides us with a competitive advantage. For example, in our potentially-registration-enabling Phase 2 clinical trial of entrectinib, STARTRK-2, we are using our lab as the FDA-required central lab to confirm the results of local genetic patient screening for enrollment, as well as to perform central testing for clinical sites without the means for local genetic screening to identify patients with molecular alterations eligible for this clinical trial that would otherwise not have been identified."

The U.S. Centers for Medicare & Medicaid Services (CMS) has approved CAP as an accreditation organization for clinical laboratories under CLIA (Clinical Laboratory Improvement Amendments). Ignyta had previously announced CLIA registration of its diagnostic laboratory, and CAP accreditation results in full CLIA certification for Ignyta’s diagnostic laboratory.

On December 14, 2015 ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT: IMUC) reported the establishment of an agreement with a major Canadian cancer cooperative group, The Canadian Brain Tumour Consortium (CBTC), for the phase 3 registrational trial of its cancer immunotherapy ICT-107 in patients with newly diagnosed glioblastoma (Press release, ImmunoCellular Therapeutics, DEC 14, 2015, View Source [SID:1234508569]). Established in 1998, and including a national investigator network of over 100 brain tumor specialists and researchers, the CBTC partners with industry to evaluate and execute clinical trials of promising new agents in a timely and cost-effective manner. The CBTC’s major goals are furthering brain tumor research and development and supporting patients and their families who are affected by glioblastoma.

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Andrew Gengos, ImmunoCellular Chief Executive Officer, commented: "Partnering with the highly respected CBTC is a critical component of our clinical trial infrastructure, and further strengthens the multi-national clinical trial network for our ICT-107 phase 3 trial. With complementary collaborations in place with cooperative groups in the US and, Europe, the CBTC collaboration can enable us to execute this international clinical program in a high quality and efficient manner. As the lead asset in our cancer immunotherapy pipeline, we believe that ICT-107 represents a valuable opportunity for ImmunoCellular. As the phase 3 program progresses, we also intend to continue to build our cancer immunotherapy platform, including our Stem-to-T-cell program, with the goal of expanding our anti-cancer technological and therapeutic approaches."

The ICT-107 phase 3 registrational trial is open for enrollment in the US with additional sites anticipated to open in Canada and Europe in the coming weeks and months.

On December 14, 2015 Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) ("Cyclacel" or the "Company"), reported the presentation of preclinical data demonstrating the molecular basis for the development of CYC065 in triple negative breast cancer (TNBC), and in particular basal-like TNBC. CYC065 is a highly-selective, second-generation cyclin dependent kinase (CDK) inhibitor targeting CDK2/9 dependent tumors (Press release, Cyclacel, DEC 14, 2015, View Source [SID:1234508697]). The data were presented at the San Antonio Breast Cancer Symposium (SABCS), taking place December 8-12, 2015.

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"We have recently reported that CYC065 can target malignancies driven by CDK2/9 dependent oncogenic and leukemogenic pathways such as MLL-rearranged leukemias and tumors overexpressing MYC", said Spiro Rombotis, Cyclacel’s President and Chief Executive Officer. "The data presented at SABCS show CYC065 could be active in breast cancer patients with a poor prognosis and that its mechanism induces breast cancer cell death by apoptosis. In addition, we have identified approved and investigational anticancer agents, including our own sapacitabine, which combine effectively with CYC065. A first-in-human, Phase 1 clinical trial with CYC065 has commenced and we look forward to reporting data from this study."

Data presented at SABCS (Program Number: P5-03-10, View Source) demonstrated in particular the mechanistic rationale for clinical development of CYC065 in basal-like TNBC, a cancer with poor prognosis frequently associated with BRCA1 mutations. Molecular characteristics of TNBC include amplification or overexpression of Cyclin E, the partner protein of CDK2, and MYC. CYC065 directs a pro-apoptotic mechanism in breast cancer cell lines, which includes transcriptional down regulation of key pro-survival and oncogenic regulators, including MCL-1 and MYC.

CYC065 was shown to rapidly induce cell death in breast cancer cell lines, while transiently inducing G1 cell cycle arrest in non-malignant breast lines. CYC065’s potent anticancer activity has been confirmed in breast cancer xenograft animal models. CYC065 effectively combined with Cyclacel’s sapacitabine in breast cancer cell lines, as was the case with seliciclib, Cyclacel’s first generation CDK2/9 inhibitor, when combined with sapacitabine.

An oral regimen of seliciclib and sapacitabine is being evaluated in an on-going Phase 1 all-comer study of patients with various advanced cancers. In previously reported initial data from this study, durable partial responses have been observed in breast, ovarian and pancreatic cancer patients with germline mutations in Homologous Recombination (HR) repair genes, specifically BRCA1 or BRCA2.

CYC065 is in a first-in-human, Phase 1 clinical trial.