I'll take that one. Other projects are progressing, but not as far along as the MEDI projects. From the 10-K:
>>Development Programs
Since inception, we have entered into numerous corporate collaborations and have pursued our own internal development projects. We expect that corporate collaborations will continue to be an important element of our business strategy. Unless specifically mentioned, we do not have commercialization rights to the intellectual property of products developed from our collaborations. The following is a summary of our development programs and related corporate collaborations:
MedImmune
In February 1999, we entered into a four-antibody corporate collaboration with MedImmune. The agreement covers the licensing of Vitaxin to MedImmune as well as the optimization of three additional antibodies, including Synagis and an antibody against IL-9. Licenses granted under this agreement are exclusive and worldwide covering the right to research, develop, sell and sublicense. The business terms of the agreement includes research and development support, potential milestone payments, royalties on the sales of products resulting from the collaboration and an equity investment. The duration of the research and development aspect of this agreement was extended through February 2004.
Synagis, MedImmune’s monoclonal antibody against RSV, is limited to the treatment of high-risk infants due to the biopharmaceutical’s high cost and requirement for intramuscular administration. By using our directed molecular evolution technology, we created several new product candidates for MedImmune that have been demonstrated in disease models to be at least 10 times more potent than Synagis. MedImmune is expected to initiate clinical trials with one of these candidates, and if successful, market it as Numax. This more potent version of Synagis could enable MedImmune to increase efficacy, address additional indications, reduce production costs and pursue additional methods for administering the protein therapeutic in order to broaden the product’s use.
Vitaxin is an anti-angiogenic antibody with potential applications in cancer and arthritis. We licensed LM609, the mouse antibody from which Vitaxin was derived, from The Scripps Research Institute. We then optimized LM609 to overcome a potential immune reaction in humans and licensed it to MedImmune.
MedImmune is now in clinical development with a second-generation version of Vitaxin that we developed using our AMEsystem technology. This version of the antibody has significantly improved affinity as well as decreased manufacturing costs. MedImmune initiated Phase I clinical trials for cancer and rheumatoid arthritis with this antibody during 2001, and may enter Phase II clinical trails in 2003.
Anti-IL-9 is an antibody with potential applications in respiratory disease including asthma.
Lilly
In December 2001, we entered into a corporate collaboration covering the optimization of an antibody and a non-antibody protein therapeutic candidate with Lilly. Under the terms of the agreement, AME received an upfront signing fee and may receive milestone payments and royalties on the sales of products resulting from the collaboration. In February 2002, an additional agreement was entered into by AME and Lilly to include the optimization of an additional antibody therapeutic candidate.
Chiron
In December 2001, we entered in to a corporate collaboration covering the optimization of a non-antibody protein therapeutic candidate with Chiron. Under the terms of the agreement, AME received an upfront signing fee and may receive milestone payments and royalties on the sales of products resulting from the collaboration.
Centocor
In May 2002, we entered into a corporate collaboration covering the optimization of an antibody protein therapeutic candidate with Centocor. Under the terms of the agreement, AME received an upfront signing fee and may receive milestone payments and royalties on the sales of products resulting from the collaboration.
CancerVax
In November 1999, we entered into a corporate collaboration covering up to four novel antibody therapeutic candidates with Cell-Matrix. During 2000, we completed the optimization of the first two compounds, and the agreement was not extended to include the remaining two potential compounds. Under the terms of the agreement, AME may receive milestone payments and royalties on the sales of products resulting from the collaboration. CancerVax acquired Cell-Matrix in January 2002. Research under this collaboration has been completed.
Biosynexus
In December 2000, we entered into a corporate collaboration covering the optimization of an antibody therapeutic candidate, HU96-110, with Biosynexus. During 2001 we completed the optimization of HU96-110, which is being developed for the treatment of staphylococcal bacterial infections. Under the terms of the agreement AME received research and development support and may receive milestone payments and royalties on the sale of products resulting from the collaboration. Research under this collaboration has been completed.
Bristol-Myers Squibb
We have entered into two separate agreements with Bristol-Myers Squibb. We have completed our optimization work under these agreements and may receive milestone payments and royalties on the sale of products resulting from the collaboration. Under the terms of the agreement, portions of the milestone payments may be creditable against royalties.
In June 1993, we entered into our initial corporate collaboration with Bristol-Myers Squibb to optimize their BR96 anti-solid tumor antibody and to develop a discovery technology program to treat tumors. Bristol-Myers Squibb renewed this collaboration in 1995. As discussed below, hBR96, our improved version of BR96, is currently in preclinical development with Seattle Genetics, a biotechnology company founded by former Bristol-Myers Squibb scientists. Based on the success of our initial collaborations, Bristol-Myers Squibb amended our agreement in 1998 to include the optimization of its anti-CD40 antibody for treating inflammatory disease. Bristol-Myers Squibb is in preclinical development with the optimized anti-CD40 antibody. Research under this collaboration has been completed.
Seattle Genetics
Seattle Genetics is in preclinical development with hBR96 for the potential treatment of cancers. After we optimized BR96 for Bristol-Myers Squibb, Seattle Genetics licensed this product candidate from Bristol-Myers Squibb. Under our original agreement with Bristol-Myers Squibb and an agreement among Bristol-Myers Squibb, Seattle Genetics and AME, we may receive milestone payments and royalties on the sale of products resulting from the collaboration. Research under this collaboration has been completed.
Novasite Pharmaceutical, Inc.
Background
AME’s majority-owned subsidiary, Novasite Pharmaceuticals, Inc. (“Novasite”), applies directed molecular evolution to small-molecule drug discovery and optimization. Novasite’s proprietary Expanded Target Drug DiscoveryTM (“ETDD”) technology works to address a limiting factor in drug discovery by simultaneously screening libraries of small molecules against libraries of drug target variants created through directed molecular evolution. Novasite’s ETDD technology enables the concurrent screening of hundreds of targets. This contrasts with a conventional method of screening compound libraries against only a single receptor target at a time. Novasite’s novel approach has the potential to screen a billion individual ligand-receptor combinations per day.
Series B Preferred Stock Financing, Affiliates and Select Option Information
During 2002, Novasite raised approximately $1.3 million, including the conversion of approximately $550,000 of debt, from a Series B Preferred Stock financings which occurred in September and November of 2002. In January 2003, Novasite raised an additional $750,000 from Series B Preferred stock financing. Following the financings, AME held a 54% interest in Novasite, and Crabtree Ventures LP, a venture firm and previous investor in Novasite, held a 40% interest in Novasite. John F. Richards, one of our directors and a director of Novasite, is the Managing Member of Crabtree Ventures, L.L.C., the general partner of Crabtree Ventures, L.P. An additional $750,000 is expected to be raised in 2003 from Series B Preferred Stock financing. The funds from the financings are expected to be used to commercialize the ETDD technology for the discovery of highly selective small-molecule drugs.
William D. Huse, our President, Chief Executive Officer and one of our directors, is the President, Chief Executive Officer and a director of Novasite. Dr. Huse has been granted options to purchase up to 800,000 shares of Novasite common stock with an exercise price equal to $0.05 per share, of which he has exercised options to purchase 16,800 shares of Novasite common stock. Approximately 70% of the total options are fully vested. Additionally, Lawrence E. Bloch, our Chief Financial Officer and Secretary, is a director of Novasite.
National Institutes of Health Grants
In March 2002, Novasite was awarded a $2.4 million grant from the National Institutes of Health (“NIH”) to support the discovery of anti-obesity drug candidates with ETDD. The grant awards $2.4 million over two years to Novasite under Phase II of the Small Business Innovation Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases branch of the NIH. Novasite plans to apply ETDD in an effort to discover novel anti-obesity drug candidates within the chemical libraries of a corporate collaborator.
In September 2000 Novasite received a grant from the NIH of $3.2 million over three years for research to develop Novasite’s proprietary technology platform. The grant was awarded to Novasite under the Bioengineering Research Partnership Program of the National Institute of Allergy and Infectious Diseases.
Aventis Pharmaceuticals, Inc.
In July 2001, Novasite entered into an agreement with Aventis Pharmaceuticals, Inc. (“Aventis”) to conduct a pilot-screening project using Novasite’s proprietary ETDD technology platform. Research under this collaboration has not been completed.
Internal Development Programs
We are using our AMEsystem technology to develop both improved versions of currently marketed biopharmaceuticals and novel human protein therapeutic candidates. We are working on improving multiple FDA-approved, currently marketed biopharmaceuticals that are already marketed by third parties and in their first-generation forms are expected to each have sales in excess of $100.0 million in 2002. We have retained full commercialization rights to these internal development projects.
AME-527
AME-527 is a humanized and optimized anti-TNF alpha MAb, in preclinical development for the treatment of rheumatoid arthritis. AME-527 binds to and neutralizes human TNF alpha, which is believed to contribute to inflammatory diseases, including rheumatoid arthritis. In AME’s head-to-head comparisons of affinity, protection from cell killing and potency, this next-generation MAb demonstrated superiority to Remicade, an FDA-approved, currently marketed anti-TNF alpha therapeutic MAb. AME-527 demonstrated greater than 15-fold higher affinity than Remicade in in vitro assays and provided greater than 10-fold increased protection from TNF alpha-mediated cell killing than Remicade in cell-based assays. Additionally, AME-527 demonstrated increased potency when compared with Remicade in a transgenic human TNF alpha polyarthritic murine model, as measured by the prevention of disease progression, or joint swelling.
AME-133
AME-133 is a humanized and optimized anti-CD20 MAb in preclinical development for the treatment of NHL. AME-133 binds to and induces death of cells expressing the CD20 antigen. In AME’s head-to-head comparisons of affinity and tumor cell killing potency, this next-generation MAb displayed superiority to Rituxan, an FDA-approved, currently marketed anti-CD20 therapeutic MAb. AME-133 exhibited greater than 10-fold higher affinity than Rituxan in in vitro models and greater than 10-fold improved killing of human cancer cells in comparison to Rituxan as demonstrated in ex vivo cell-based assays.
AME-359
In September 2001, we announced the award of a $1.0 million grant from the NIH to support the development of AME-359, a therapeutic enzyme BChE we licensed from the University of Nebraska Medical Center in March 2000 and the Mayo Clinic in January 2001, for the potential treatment of acute cocaine toxicity and chronic cocaine addiction. BChE is a naturally occurring human serum enzyme that inefficiently breaks down cocaine to inactive byproducts. Using the AMEsystem, AME has developed AME-359 demonstrating over 100-fold increased activity compared with naturally occurring BChE and has taken the resulting product candidate into preclinical development. AME has conducted animal models demonstrating engineered improvements in AME-359’s catalytic rate that improve the enzyme’s ability to neutralize the toxic effects of cocaine in vivo by greater than 250-fold in comparison to the naturally occurring enzyme. <<
Cheers, Tuck |
