Pfizer Inc. Message Board

Nice to see someone else picking up the tab for this trial.

Sentiment: Strong Buy

Another great patent just issued to Astex.
United States Patent 8,445,502
Bearss , et al. May 21, 2013

Pharmaceutical formulations comprising salts of a protein kinase inhibitor and methods of using same
Abstract
The present invention relates to pharmaceutical formulations comprising the protein kinase inhibitor, MP470, and methods of using same in treating conditions involving undesirable cell proliferation, such as cancer.

Inventors: Bearss; David J. (Cedar Hills, UT), Joshi-Hangal; Rajashree (Pleasanton, CA), Liu; Xiao-Hui (Sandy, UT), Phiasivongsa; Pasit (Brentwood, CA), Redkar; Sanjeev G. (Hayward, CA), Vankayalapati; Hariprasad (Draper, UT)
Applicant: Name City State Country Type
Bearss; David J. Joshi-Hangal; Rajashree Liu; Xiao-Hui Phiasivongsa; Pasit Redkar; Sanjeev G. Vankayalapati; Hariprasad Cedar Hills Pleasanton Sandy Brentwood Hayward Draper UT CA UT CA CA UT US US US US US US

Assignee: Astex Pharmaceuticals, Inc. (Dublin, CA)
Appl. No.: 12/906,640
Filed: October 18, 2010



Current U.S. Class: 514/267
Current International Class: A01N 43/54 (20060101); A61K 31/505 (20060101)
Field of Search: 514/267

References Cited [Referenced By]

Foreign Patent Documents

WO 2005/037825 Apr., 2005 WO

Primary Examiner: Leeser; Erich A
Attorney, Agent or Firm: Seed IP Law Group PLLC

Parent Case Text



Claims

What is claimed is:
1. A method of treating small cell lung cancer in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of an oral pharmaceutical formulation comprising a pharmaceutically acceptable excipient and a hydrochloride sale of MP470, wherein MP470 has the following structure: ##STR00007## , wherein the pharmaceutical formulation is delivered in combination with at least on

The results could come out any day. I expect a pop too.

CLDX could hit $14 this week imo.

This phase I trial studies the side effects and immune response to DEC-205/NY-ESO-1 fusion protein CDX-1401 and decitabine in patients with myelodysplastic syndrome or acute myeloid leukemia. DEC-205-NY-ESO-1 fusion protein, called CDX-1401, is a full length NY-ESO-1 protein sequence fused to a monocolonal antibody against DEC-205, a surface marker present on many immune stimulatory cells. This drug is given with another substance called PolyICLC, which acts to provoke any immune stimulatory cells which encounter the NY-ESO-1-DEC-205 fusion protein to produce an immune response signal against NY-ESO-1. Immune cells which have thus been primed to react against NY-ESO-1 may then attack myelodysplastic or leukemic cells which express NY-ESO-1 after exposure to the drug decitabine. The chemotherapy drug decitabine is thought to act in several different ways, first, it may directly kill cancer cells, secondly, the drug can cause cancer cells to re-express genes that are turned off by the cancer, including the gene for NY-ESO-1. Giving DEC-205/NY-ESO-1 fusion protein (CDX-1401) and polyICLC together with decitabine may allow the immune system to more effectively recognize cancer cells and kill them.

Sentiment: Strong Buy

DEC-205/NY-ESO-1 Fusion Protein CDX-1401and Decitabine in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia
This study is not yet open for participant recruitment.
Verified May 2013 by Roswell Park Cancer Institute
Sponsor:
Roswell Park Cancer Institute
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer InstituteClinicalTrials.gov Identifier:
NCT01834248
First received: April 12, 2013
Last updated: May 7, 2013
Last verified: May 2013
History of Changes

Thank you Long. This is fantastic news.

Sentiment: Strong Buy

Management has been playing possum for a few months. I think something big could happen soon.

Sentiment: Strong Buy

Granuloma cells in chronic inflammation express CD205 (DEC205 ...
by H Ohtani - 2013 -
Feb 22, 2013 – Keywords: antigen presenting cells, CD205 (DEC205), granuloma, ... and granulomatous inflammation of the lung associated with lung cancer ...

DEC-205-mediated antigen targeting to steady-state dendritic cells induces deletion of ... Boston, MA 3Medical Oncology, Dana-Farber Cancer Institute, Boston, MA ... characterized by T cell-mediated destruction of the pancreatic islet beta cells. ... Treatment with anti-DEC-205 linked to NRP-V7, a superagonist mimotope of ...

Good recap Fish.

Blockbuster potential.

Targeting of DEC-205 on human dendritic cells results in efficient MHC class II–restricted antigen Katrin Birkholz1, Michael Schwenkert2, Christian Kellner3, Stefanie Gross1, Georg Fey2, Beatrice Schuler-Thurner1, Gerold Schuler1, Niels Schaft1, and Jan Dörrie1
+ Author Affiliations
1Department of Dermatology, University Hospital Erlangen, Erlangen, Germany;
2Department of Genetics, University of Erlangen-Nuremberg, Erlangen, Germany; and
3Division of Stem Cell Transplantation and Immunotherapy, 2nd Medical Department, Christian-Albrechts-University, Kiel, Germany
Abstract
The use of dendritic cells (DCs) in therapeutic cancer vaccination requires their loading with tumor-specific antigen(s). DEC-205, a phagocytosis receptor mediating antigen uptake, is associated with CD8+ T-cell responses in mice. Here we fused an anti–DEC-205scFv to an HLA-DP4–restricted epitope from the tumor antigen MAGE-A3, and examined the suitability and efficacy of DEC-205 to deliver a helper epitope to human monocyte-derived DCs (moDCs). The construct specifically bound DEC-205 on human moDCs without negative impact on DC phenotype and function. We measured antigen presentation with specific autologous CD4+ T cells, generated by TCR-RNA transfection. DEC-205 targeting resulted in significant major histocompatibility complex class II–restricted antigen presentation, and was superior to loading DCs by electroporation of mRNA encoding endosome-targeted MAGE-A3-DCLAMP or by direct peptide pulsing. Anti–DEC-205scFv-MAGE-A3 was presented 100 times more efficiently than the control constructs. DC maturation before or during incubation with anti–DEC-205scFv-MAGE-A3 reduced the interleukin-10/interleukin-2 ratio. Moreover, we successfully applied the DEC-205 targeting strategy to moDCs from malignant melanoma patients. Again, DEC-205–targeted mature DCs (mDCs) presented the antigen more efficiently than peptide-pulsed DCs and maintained their stimulatory capacity after.....

Whip, this is one time we have to disagree.

The DEC-205 Receptor: DEC-205 (CD205) is part of the mannose receptor family, but is expressed on distinct dendritic cell populations. The pioneering work of Drs. Ralph Steinman and Michel Nussenzweig at The Rockefeller University, New York has demonstrated that this receptor may be exceptionally effective for APC targeting using models of cancer, infectious disease and autoimmune disease. The first product candidate using a human antibody to target DEC-205 receptors is CDX-1401, a vaccine targeting the tumor-associated antigen, NY-ESO-1 to DEC-205 receptor with the human mAb 3G9. CDX-1401 is currently in Phase 1/2 development for the treatment of cancers known to express NY-ESO-1, including cancers of the bladder, breast, ovary, non-small cell lung cancer, myeloma, sarcoma and melanoma. Additional programs targeting DEC-205 for vaccination against HIV and other diseases are also in preclinical development.

Here is an excerpt from Nussenzweig's work:
A second area of interest for the Nussenzweig lab is the physiological function of dendritic cells. To examine the function of dendritic cells in the steady state, he and his colleagues devised an in vivo antigen delivery system that uses a monoclonal antibody and a dendritic cell-restricted endocytic receptor, DEC-205. This route of antigen delivery is several orders of magnitude more efficient in inducing T cell activation and cell division than free peptide in strong adjuvants. But the activation response is not sustained, and T cells become unresponsive to systemic rechallenge with antigen. Co-injection with anti-CD40 agonistic antibody changes the outcome from tolerance to prolonged T cell activation and immunity, indicating that in the steady state, the primary function of dendritic cells is to maintain peripheral tolerance.

Meant to say "results are positive?"