Malignant Melanoma

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BioLume
Presentation January 10, 2007
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BioLume Mission
..to develop and commercialize a broad library
of proprietary bioluminescent proteins with
multiple first-in-class applications in
diagnostic imaging, food, beverage, and
cosmetics..
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BioLume Imaging Patents

• Detection and visualization of neoplastic
  tissues and other tissues
• U.S. 6,416,960 issued July 9, 2002
• U.S. 6,596,257 issued July 22, 2003
• U.S. 09/746485 filed December 22, 2000
• Broad claims e.g., A diagnostic system
  containing a bioluminescence generating system
• Backed up by broad composition of matter patents

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What is Bioluminescence?

Bioluminescence is light produced by a chemical
reaction within a living organism
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Bioluminescent Proteins

Visible light
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Bioluminescent Proteins
BioLumes bioluminescent proteins were cloned
from various deep-sea marine organisms

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Bioluminescent Proteins
Sardines, Herring, Haddock, Tuna, Salmon, and
Mackerel all have diets rich in bioluminescent
organisms and contain luciferases and their
substrate coelenterazine

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Bioluminescent Proteins
Food squid observed during fishery collection

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Bioluminescent Protein Safety

These proteins have already been tested for skin,
eye, and oral toxicity (both acute and
sub-acute) These proteins were negative for
mutagenicity in the Ames test. Many
pharmaceutical and university research
laboratories have maintained animals expressing
Luciferase, with no reports of toxicity or
failure of animals or cells to thrive due to
their presence. Coelenterazine is a natural
antioxidant

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Molecular Imaging

Molecular imaging represents a paradigm shift in
the focus of medical imaging from the
visualization of anatomy and physiology to the
study of metabolic and physiological processes
e.g., cancers, often in real time
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Molecular Imaging
Recent advances in biotechnology have enabled in
vivo molecular imaging of luciferase reporter
proteins in living animals by using a cooled
charge-coupled device (CCD) camera.

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Bioluminescent Imaging
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Molecular Imaging

Because bioluminescence imaging has minimal
background activity, this technology is very
sensitive for detecting light emitted from
luciferases
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Bioluminescent Imaging
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Bioluminescence Molecular Imaging with renilla
luciferase
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Bioluminescent Imaging
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Bioluminescent Imaging
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Bioluminescent Imaging
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Bioluminescent Imaging
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Skin Cancer Facts

• gt1 million new cases of skin cancer will be
  diagnosed in the US this year (gt10k will die)
• 1 in 5 Americans will develop skin cancer during
  their lifetime (BCC, SCC, or melanoma)
• 1 in 65 Americans were likely to develop
  melanoma during their lifetime
• Melanoma incidence has increased 690 since 1950
• Melanoma is the second most common cancer in
  women aged 20 to 29
• Source American Academy of Dermatology

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Skin Cancer Detection

• Screening for skin cancer is a visual exam by
  patient or dermatologist
• Suspicious lesions get a biopsy
• Highly specific antibodies for melanoma are
  known and generically available
• There are no skin cancer screening kits on the
  market today

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Immunology of Melanoma

• There are unique surface antigens which
  characterize melanoma cells
• These unique antigens can be used to target
  highly specific antibodies, for therapy or
  detection

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Immunology of Melanoma

• One type of surface antigen is a ganglioside
  (GM3)
• Antibodies have been made which are directed
  against these gangliosides as well as other
  melanoma surface antigens

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Selective melanoma antibody kill melanoma cells
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Bioluminescent Melanoma Detection

Luciferases can be expressed with antibodies to
melanoma surface antigen(s) Or Luciferases can
be chemically conjugated to the melanoma
antibodies
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Summary

• Product development opportunity combining known
  antibodies and developed bioluminescent proteins
  (no research required)
• Patented bioluminescent proteins
• Focused on an unmet medical need
• Large market opportunity