Tuesday, February 1, 2011

Astellas Oncology: Dora's Estrellas in Astellas' Star-Pocket

Many of you may recall the spring of 2010 when Astellas tried to acquire OSI Pharmaceuticals - the barbs flew, as expected, until tons of Yens (to the tune of $4B) were offered to calm OSI and bring it into the Astelles family.  That event signaled the maturing of Astellas as an oncology firm. 
Today, Agensys, OSI and a cherry-picked winner, Medivation, have created an impressive portfolio for Astellas Oncology.  Astellas (us-TALL-es) Pharma itself is a young company.  It was formed through the merger of two legacy Japanese Pharmaceuticals, Fujisawa and Yamanouchi, on 1 April 2005.

<Dora's star pocket and star friends>

Noisy Star (the loudest star) = OSI Pharmaceuticals
Glowy (the bright light star) = Agensys
Woo-hoo Star (the peekaboo star) = Medivation
Morph Star (the explorer star that can change its shape)! = Astellas itself
Tool Star (the star with all the cool gadgets) = partners - Seattle Genetics & Abgenix
Saltador (the jumping star) = coming onboard for phase II/III - Ferring and others
Rocket and Hero stars = just off the horizon!

Agensys ‘Glowy’ star:  Agensys (a-GEN-SIS), originally known as UroGenesys, was spun-off from UCLA and established as a subsidiary of Astellas in 1996 to develop fully humanized monoclonal antibodies against solid tumors targeting surface antigens discoved at UCLA by Arie Belldegrun and others.  The lead candidate licenced from UCLA was the prostate stem cell antigen, or PSCA.  Later Astellas bought Agensys for  $537M, some say, it merged into it.[...]  Today, the strength of Agensys is its xenomouse technology, in-licenced from Abgenix (now Amgen Fremont), to develop fully humanized monoclonal antibodies.  The other key advantage is their collection of potential cancer targets identified and validated through a collection of actual patient samples.

Astellas Oncology Pipeline (11/2010)
 (Two marketed products are Eligard and Tarceva)

Agensys monoclonals: 
  • AGS-1C4D4, anti-prostate stem cell antigen (anti-PSCA) monoclonal antibody, is in phase 2 trial for pancreatic cancer
  • ASP6183 (AGS-8M4), anti-human chondrolectin (AGS-8) monoclonal antibody, was in Phase 2 for ovarian cancer (development suspended)
  • AGS-16M8F and antibody-drug conjugate (ADC) entered phase 1 clinical trial for metastatic renal cancer in Sept 2010.  It has monomethyl auristatin F (MMAF) cytotoxin conjugated to fully human monoclonal antibody directed to ectonucleotide pyrophosphatase/phosphodiestrase 3 (ENPP3) which is upregulated in majority of renal cancers.  MMAF is conjugated  using Seattle Genetics' non-claveable linker that allows release of toxin only after the ADC is inside a (tumor) cell.
  • AGS-16M18, a fully human IgG1 monoclonal antibody that binds AGS-16 on the surface of kidney cancer cells
  • AGS-16M18, AGS-16M8F and ASG-5ME are in early phase 1 trials.  The latter two are ADC conjugates; ASG-5ME is co-developed with Seattle Genetics.
OSI oral compounds:
  • erlotinib (Tarceva), HER1/EGFR tyrosine kinase inhibitor, is in Phase 3 trial for NSCLC (first line for patients with EGFR mutation)
  • OSI-906, IGF-1R/IR tyrosine kinase inhibitor, is in Phase 3 trial for Adrenocortical carcinoma and Phase 2 for Ovarian cancer, NSCLC and Hepatocellualr carcinoma.
  • OSI-027, mTOR kinase inhibitor, is in Phase 2 for renal cellular cancer
  • MDV3100 (Medivation's compound) triple andogen antagonist, is in late stage Phase 3 trials
  • ASP3550 is a three-month formulation of degarelix (Ferring's compound).  It is a GnRH antagonist and is in Phase 2 trial for prostate cancer in Japan.  The original compound, degarelix is already in US market as Firmagon for prostate cancer.
  • AC220 (Ambit's compound), FLT3 kinase oral compound, is in Phase 2 for Acute myeloid leukemia.
  • YM155, suppresses Survivin, is in Phase 2 for breast cancer, non-hodgkin's lymphoma and melanoma
  • AKP-002 (in-licenced from ASKA) is in early stage for benign prostatic hyperplasia (BPH)

  • Astellas eyes oncology growth. By Dominic Tyer. InPharm, April 4, 2010 [link]
  • Therapeutic potential of AGS-PSCA: A fully human monoclonal antibody to prostate stem cell antigen for treating prostate and pancreatic cancers.  AACR Meeting Abstracts, Apr 2005; 2005: 164. [AACR link]
  • From XenoMouse technology to panitumumab, the first fully human antibody product from transgenic mice. by: Aya Jakobovits, Rafael G. Amado, Xiaodong Yang, Lorin Roskos, Gisela Schwab.  Nature biotechnology 25(10):2007;1134-1143. [DOI][GoogleScholar]

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