Replies to post #130497 on Biotech Values

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CLDX initiates Phase I trial with CDX1127, a fully-human monoclonal antibody


November 8, 2011 - 8:00 AM EST
CLDX 2.89 0.00

Celldex Therapeutics Announces Initiation of Phase 1 Clinical Trial of CDX-1127

Celldex Therapeutics, Inc. (Nasdaq: CLDX) today announced initiation of a Phase 1 study of its therapeutic human antibody candidate, CDX-1127, in patients with selected malignant solid tumors or hematologic cancers. CDX-1127 is a fully human monoclonal antibody that binds CD27, an important co-stimulatory molecule on T cells. CDX-1127, an agonist antibody designed to activate patients’ immune cells against their cancer, has shown potent efficacy in several preclinical models. In addition, CD27 is over-expressed in certain lymphomas and leukemias and can be directly targeted by CDX-1127.

The Phase 1 study is designed to test 5 escalating doses of CDX-1127 to determine a Phase 2 dose for further development based on safety, tolerability, potential activity and immunogenicity. The study will accrue approximately 30 patients in each of the two arms, either solid tumors or lymphomas/leukemias. Patients will have received all appropriate prior therapies for their specific disease. The trial design incorporates both single dosing and multiple dosing regimens at each dose level. The study, anticipated to complete accrual in approximately 1 year, is being conducted at multiple clinical sites in the United States.

“The CDX-1127 program is our first therapeutic antibody and demonstrates our development capabilities to rapidly and successfully translate concept into clinical trials,” said Anthony S. Marucci, President and Chief Executive Officer of Celldex Therapeutics. “We believe strongly in the opportunities for immune modulating antibodies and the pre-clinical data generated with CDX-1127 through our collaboration with University of Southampton, UK has been very encouraging.”

About CDX-1127

CDX-1127 is a human monoclonal antibody program targeting CD27, a member of the tumor necrosis factor (TNF) receptor superfamily. CD27 is a critical molecule in the activation pathway of lymphocytes.

It acts downstream from CD40 and may provide a novel way to regulate the immune responses. CD27 is a co-stimulatory molecule on T cells and is over-expressed in certain lymphomas and leukemias. Previously published data by Professor Martin Glennie, Ph.D., Director of Cancer Sciences, Tenovus Research Laboratory, University of Southampton, UK, has demonstrated that targeting CD27 with monoclonal antibodies in mice is highly effective at promoting anti-cancer immunity. Celldex presented more recent preclinical in vitro and animal data with CDX-1127 at the 2011 American Association for Cancer Research (AACR) 101st Annual Meeting demonstrating that targeting CD27 receptors with CDX-1127 can increase the numbers of responding T cells and can mediate significant anti-tumor activity. CDX-1127 was also shown to directly impact tumor cells expressing CD27. The solid tumor indications that can enroll into the Phase 1 study include; refractory patients with metastatic melanoma, renal (clear) cell carcinoma, hormone-refractory prostate adenocarcinoma, ovarian and colorectal adenocarcinoma, and non-small cell lung cancer.

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[mcbio]

CLDX - initiates rindo Phase 3

http://finance.yahoo.com/news/-Celldex-Initiates-ACT-IV-bw-2060126512.html?x=0

Celldex Initiates ACT IV, a Pivotal International Phase 3 Trial of Rindopepimut in Patients with Glioblastoma

- Vaccine Targets Molecularly Defined Population– Patients with EGFRvIII-positive Glioblastoma -

NEEDHAM, Mass.--(BUSINESS WIRE)-- Celldex Therapeutics, Inc. (NASDAQ: CLDX - News) today announced that it has launched a pivotal, randomized, double-blind, controlled Phase 3 trial of rindopepimut in patients with surgically resected epidermal growth factor variant III (EGFRvIII)-positive glioblastoma, the “ACT IV Study.” US investigators have started screening patients for inclusion in the trial that is expected to enroll up to 440 patients internationally to recruit 374 patients with Gross Total Resection (GTR) for the primary analysis. Rindopepimut is a therapeutic cancer vaccine candidate that targets the tumor-specific oncogene EGFRvIII, which confers an enhanced capacity for unregulated tumor growth and which is present in many cancer cell types, but not present at significant levels in normal cells. Expression of EGFRvIII is linked to poor long term survival regardless of other factors such as extent of resection and age. EGFRvIII has been shown by polymerase chain reaction (PCR) analysis to be expressed in approximately 31% of glioblastoma tumors.

“Rindopepimut has demonstrated significant potential to offer a new treatment option to patients suffering from glioblastoma, a disease with an extremely poor prognosis and few treatment options,” commented Thomas Davis, M.D., Chief Medical Officer of Celldex. “Celldex has worked diligently with both US and European regulatory authorities to design the ACT IV trial to rigorously evaluate the addition of rindopepimut to standard of care in EGFRvIII-positive glioblastoma patients. This international Phase 3 study will be conducted in a blinded fashion, comparing rindopepimut against a control arm receiving only a low-dose of keyhole limpet hemocyanin (KLH). KLH is a component of rindopepimut and was selected due to its ability to generate a similar injection site reaction to that observed with the rindopepimut vaccine,” added Dr. Davis.

“Given the consistent encouraging clinical data from multiple previous trials of rindopepimut showing clear improvements in median Overall Survival and median Progression Free Survival to both matched historical controls and historical data with the standard of care treatment, we look forward to expanding on this body of evidence in the pivotal ACT IV study,” said Anthony Marucci, President and CEO of Celldex. “The initiation of ACT IV is an important milestone for Celldex and we expect to make substantial progress in this trial throughout 2012. We are also planning to further expand on the clinical development program for rindopepimut in 2011 by initiating the Phase 2 ReACT study of rindopepimut in combination with Avastin® in patients with recurrent or refractory glioblastoma.”

About the ACT IV Study

The ACT IV study is a randomized, double-blind, controlled study of rindopepimut plus GM-CSF added to standard of care temozolomide in patients with newly diagnosed, surgically resected, EGFRvIII-positive glioblastoma. Patients will be randomized after the completion of surgery and standard chemoradiation. The treatment regime includes a vaccine priming phase post-radiation followed by an adjuvant temozolomide phase and a vaccine maintenance therapy phase. Patients will be treated until disease progression or intolerance to therapy. The primary objective of the study is to determine whether rindopepimut plus GM-CSF improves the overall survival of patients with newly diagnosed EGFRvIII positive glioblastoma after GTR when compared to treatment with the current standard of care, temozolomide. A total of approximately 440 patients will be enrolled at over 150 centers worldwide to recruit 374 patients with GTR to be included in the primary analysis. Secondary endpoints include: progression free survival; safety and tolerability of rindopepimut and GM-CSF in combination with temozolomide; neurologic status and quality of life. Patients will be stratified based upon geographic region, RPA class prognostic factors and MGMT methylation status.

Clinical Data Supporting Rindopepimut in Glioblastoma

Rindopepimut has been evaluated in three successful clinical studies of patients with EGFRvIII-positive glioblastoma to date: the ACTIVATE, ACT II and ACT III studies. Notably, rindopepimut demonstrated consistent and statistically significant increased survival rates across all three studies. In ACTIVATE, ACT II and ACT III, median progression free survival (PFS) from diagnosis was 14.2, 15.3 and 12.3 months, while median overall survival (OS) from diagnosis was 24.6, 24.4 and 24.6 months, respectively. The results were not statistically different between these studies. Mature data from the ACT III study were presented at the Society for Neuro-Oncology conference, indicating that 52% of the patients were alive at two years, while 50% of the enrolled patients in both earlier studies were alive at two years from diagnosis. These data compare favorably to a cohort of patients (historical controls) treated at M.D. Anderson Cancer Center and matched for eligibility including having glioblastoma expressing the EGFRvIII oncogene, where median PFS was 6.4 months and median OS was 15.2 months, with less than 6% of patients alive after 2 years. In addition, the four-year survival rate for ACTIVATE is 22%, while follow-up in ACT II and ACT III is ongoing.

In ACT III, the results for the predefined primary endpoint, 66% Progression Free Rate (PFR) at approximately 8.5 months post-diagnosis, show a statistically significant improvement (p=0.0168) over a predetermined estimate of 53%, which is beyond the range of expected progression-free survival for glioblastoma patients receiving standard of care (SOC). Published results for SOC and from matched historical controls are 45% and 29%, respectively, for PFR at 8.5 months post-diagnosis.

In all clinical trials to date, rindopepimut has been generally well tolerated with injection site reaction being the most frequently observed side effect.

About Rindopepimut

Rindopepimut is an investigational immunotherapeutic vaccine that targets the tumor-specific molecule epidermal growth factor receptor variant III (EGFRvIII). EGFRvIII is a mutated form of the epidermal growth factor receptor (EGFR) that is only expressed in cancer cells and not in normal tissue and is a transforming oncogene that can directly contribute to cancer cell growth. Expression of EGFRvIII is linked to poor long term survival regardless of other factors such as extent of resection and age. EGFRvIII has been shown by polymerase chain reaction (PCR) analysis to be expressed in approximately 31% of glioblastoma tumors.

About Celldex Therapeutics, Inc.

Celldex Therapeutics is the first antibody-based combination immunotherapy company. Celldex has a pipeline of drug candidates in development for the treatment of cancer and other difficult-to-treat diseases based on its antibody focused Precision Targeted Immunotherapy (PTI) Platform. The PTI Platform is a complementary portfolio of monoclonal antibodies, antibody-targeted vaccines and immunomodulators used in optimal combinations to create novel disease-specific drug candidates. For more information, please visit http://www.celldextherapeutics.com.

[mcbio]

CLDX - completes accrual for CDX-011 Phase 2b breast cancer trial

[I view the readout from this Phase 2b trial in 1H12 as a very big binary event for CLDX. Who knows if the results will be positive but I thought the Phase 2a results were promising (#msg-44473380 ) and have CLDX as one of my largest holdings. Curious to hear any skeptical takes on the prior Phase 2a data, other than fact that trial was single-arm, or chances of success of the ongoing Phase 2b.]

http://finance.yahoo.com/news/Celldex-Completes-Accrual-CDX-bw-508915165.html?x=0

Celldex Completes Accrual of CDX-011 Phase 2b “EMERGE” Study in Advanced Breast Cancer

NEEDHAM, Mass.--(BUSINESS WIRE)-- Celldex Therapeutics, Inc. (Nasdaq: CLDX - News) today announced that it has completed accrual of the EMERGE study, a randomized Phase 2b study evaluating CDX-011 (glembatumumab vedotin) in patients with previously treated metastatic or locally advanced breast cancer. The Company anticipates presenting results at an appropriate scientific conference in the first half of 2012.

“The median survival of patients with metastatic breast cancer is two to three years and for patients with "triple-negative" disease, the prognosis is even more grim,” said Thomas Davis, MD, Chief Medical Officer of Celldex Therapeutics. “A previous Phase 1/2 single arm study of CDX-011 demonstrated encouraging results in women whose tumors express GPNMB, a molecule associated with worse outcome. These results included disease regression and improvements in progression free survival (PFS) compared to historical controls. We are very pleased with the rapid accrual of this study and expect the data will continue to support the potential of CDX-011 as a much needed new treatment option for patients facing these difficult to treat breast cancers.”

CDX-011 is an antibody-drug conjugate targeting glycoprotein NMB (GPNMB) which is over expressed in several cancers including breast cancer, melanoma, lymphomas/leukemias and squamous carcinoma of the lung. The randomized, multi-center, controlled trial enrolled advanced and heavily pre-treated breast cancer patients who are unlikely to benefit from any approved therapies and whose tumors are confirmed to express GPNMB via a centralized diagnostic assay. It is anticipated that a significant portion of the enrolled patients will have triple-negative disease, since GPNMB is frequently expressed in this patient population. Patients were randomized (2:1) to receive either CDX-011 or single-agent “Investigator’s Choice” chemotherapy. Patients randomized to receive Investigator’s Choice are allowed to cross-over to CDX-011 following disease progression. Activity endpoints include response rate (RR) and PFS. The study is being conducted at approximately 20 academic and community sites across the U.S.

About Breast Cancer

Breast cancer is the most common cancer in women and a leading cause of death in the United States. According to the American Cancer Society, more than 180,000 women were diagnosed with invasive breast cancer in 2009 with more than 40,000 deaths attributed to this disease. Despite recent advances in therapy, the median survival of patients with metastatic breast cancer is 2 to 3 years, while patients with "triple-negative" or "basal-like" breast cancer have limited treatment options due to lack of over-expression of HER2, estrogen and progesterone receptors and have poorer outcomes. Therefore, a significant unmet need remains for novel therapeutic approaches for patients with locally advanced and metastatic breast cancer who have failed other therapies.

About CDX-011

CDX-011 (glembatumumab vedotin) is an antibody-drug conjugate (ADC) that consists of a fully-human monoclonal antibody, CR011, linked to a potent cell-killing drug, monomethyl-auristatin E (MMAE). The ADC technology, comprised of MMAE and a stable linker system for attaching it to CR011, was licensed from Seattle Genetics, Inc. The ADC is designed to be stable in the bloodstream. Following intravenous administration, CDX-011 targets and binds to GPNMB, a specific protein that is expressed in breast cancer and other tumor types, and which promotes the migration, invasion and metastasis of breast cancer. Upon internalization into the targeted cell, CDX-011 is designed to release MMAE from CR011 to produce a cell-killing effect. CDX-011 has been shown to be well tolerated and active, with observed objective responses in two positive Phase 1/2 trials in metastatic breast cancer and advanced melanoma. In May 2010, the U.S Food and Drug Administration (FDA) granted Fast Track designation to Celldex’s CDX-011 for the treatment of advanced, refractory/resistant GPNMB-expressing breast cancer.

About Celldex Therapeutics, Inc.

Celldex Therapeutics is the first antibody-based combination immunotherapy company. Celldex has a pipeline of drug candidates in development for the treatment of cancer and other difficult-to-treat diseases based on its antibody focused Precision Targeted Immunotherapy (PTI) Platform. The PTI Platform is a complementary portfolio of monoclonal antibodies, antibody-targeted vaccines and immunomodulators used in optimal combinations to create novel disease-specific drug candidates. For more information, please visit http://www.celldextherapeutics.com.