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Seattle Genetics Presents Preclinical Data on Antibody-Drug Conjugate (ADC) Technology

Strategic Insights

— 2 min read

Seattle Genetics, Inc. announced that it will present data from several of its preclinical programs, including its novel ADC technology, in five poster sessions during the 2004 Annual Meeting of the American Association for Cancer Research (AACR) in Orlando, Florida. The company's ADC technology is comprised of highly potent drugs and stable linker systems, and has shown promising results in preclinical studies.

Seattle Genetics' ADC technology has the potential to revolutionize cancer treatment by delivering a cell-killing drug directly to a tumor cell, while minimizing exposure to normal cells. The company's second-generation ADC technology utilizes highly potent Auristatin derivatives, such as monomethyl Auristatin E (MMAE) and monomethyl Auristatin F (MMAF), which have been synthetically modified to enhance efficacy and lower toxicity. The data demonstrate that MMAF is less potent than MMAE as a free drug, but when linked to an internalizing monoclonal antibody, the ADCs utilizing MMAF are significantly more potent than corresponding ADCs utilizing MMAE.

Key Takeaways:

  • Seattle Genetics' ADC technology utilizes highly potent Auristatin derivatives, such as MMAE and MMAF, which have been synthetically modified to enhance efficacy and lower toxicity.
  • The company's second-generation ADC technology has shown promising results in preclinical studies, with ADCs utilizing MMAF demonstrating significantly more potent activity than corresponding ADCs utilizing MMAE.
  • SGN-35, an anti-CD30 ADC, has been shown in preclinical studies to have potent and selective activity against CD30-positive malignancies.
  • The company has optimized the therapeutic potential of SGN-35 by assessing the impact of reduced drug loading, resulting in a longer half-life and reduced toxicity.
  • SGN-75, an anti-CD70 ADC, has shown promise in preclinical models, with the CD70 antigen expressed in high density on renal cancer and SGN-75 demonstrating potent antitumor activity.
  • SGN-30, a monoclonal antibody targeting the CD30 antigen, has shown synergistic activity in combination with conventional chemotherapeutics commonly used in CD30-positive malignancies.

Statistics:

  • 8 potential sites for drug attachment on monoclonal antibodies
  • 2, 4, 6, and 8 drugs per antibody evaluated in preclinical models
  • 623 presentations showing that MMAF is less potent than MMAE as a free drug
  • 624 presentations demonstrating that ADCs utilizing MMAF are significantly more potent than corresponding ADCs utilizing MMAE
  • 2258 presentations showing synergistic activity of SGN-30 in combination with chemotherapy

Sources:

  • Business Editors & Health/Medical Writers 2004 Annual Meeting of the American Association for Cancer Research
  • Seattle Genetics, Inc. press release, March 24, 2004
  • Abstract #623, Seattle Genetics, Inc.
  • Abstract #624, Seattle Genetics, Inc.
  • Abstract #625, Seattle Genetics, Inc.
  • Abstract #2258, Seattle Genetics, Inc.
  • Seattle Genetics, Inc. website, www.seattlegenetics.com.

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