Case StudySignature Genomic Laboratories, LLC

Spokane WA

Bassem A. Bejjani, MD, FACMG

Co‐founder and Chief Medical Officer

Signature Genomic Laboratories, LLC

The Founders

•Sacred Heart Medical Center Spokane

•PAML

•Lisa G. Shaffer, PhD and Bassem A. Bejjani, MD

Sacred Heart Medical Center Spokane

•Founded by the Sisters of Providence in 1886 as a 31‐bed, wood‐framed structure. 

Sacred Heart Medical Center Spokane

Sacred Heart Medical Center & Children’s Hospital is part of Providence Health & Services, which includes 27 hospitals; more than 35 non‐acute facilities; physician clinics; a health plan; a liberal arts university; 45,000 employees; and numerous other health, housing and education services in Alaska, Montana, Washington, Oregon and California. The corporate headquarters are in Seattle.

PAML

• Largest independent laboratory in the Northwest.

• Annual revenues: >$150 million per year with partnerships.

• Provides reference testing services to over 100 hospitals throughout the West.

• A history of successful laboratory joint ventures with hospitals.

• Internationally recognized staff of Ph.D. and M.D. scientists.

Lisa G. Shaffer, PhD and Bassem A. Bejjani, MD

• Worked together at Baylor College of Medicine.

• Bejjani boarded in pediatrics, medical genetics, molecular genetics, and cytogenetics.

• Shaffer boarded in cytogenetics.

• Together have over 25 years of experience and have published more than 200 manuscripts.

• Recognized as leaders in the array‐CGH field.

The Field

Clinical Cytogenetics

Indications for Chromosome Study

• Problems of early growth and development

• Stillbirth and neonatal death

• Fertility problems

• Family history

• Pregnancy in a woman of advanced age

• Neoplasia

Market Size (US only)• Legacy Market

– 3% of the population has mental retardation (~9M people).

– Only ~20% have a diagnosis.– All should have a array CGH ($14.8B).

• Renewable Market– ~120,000 birth/year with birth defect

($200M/year).– ~400,000 prenatal karyotypes/year ($660M).

History of Human Cytogenetics

• “Dark Ages” (prior to 1952)• Hypotonic Period (1952‐1959)• Trisomy Period (1959‐1974)

• Banding Era (1974‐1989)• Molecular Era (1989‐ ?)

Therman E, Susman M (1993) Human Chromosomes, 3rd ed. Springer-Verlag, New York

Mb No. of Genes

Genome 3,000 20,000

Avg. Chromosome 150 1,000-2,000

Avg. Band = 400 bands/hg

7.5 50-100

Prophase = 1,000 bands/hg

3.0 25-50

Limits of resolution 2.0 15-30

400 550 850hg = haploid genome

The Banding Era

Limitations to Conventional Cytogenetics and FISH

•Low resolution/Labor intensive•High resolution/Labor intensive

Applications of DNA microarrays

• Gene expression profiling• Genotyping (SNP detection)• DNA re‐sequencing• CGH

Traditional CGH Array CGH

Control Test Control Test

Picture courtesy of Brynn Levy, Ph.D.

Arrayed clones

CGH Microarray Methodology

Cloned human DNA (BAC/PAC, Oligos)

CGH Microarray MethodologyControl genomic

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A Brief History of Signature Genomics 

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A Brief History of Signature Genomics 

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esIngredients for Growth

• The vision of the founding investors.

• The support of the founding investors.

• Knowledge of the market.

• Knowledge of the technology.

• Key hires.

• Marketing strategy.

• Continuous innovation.

Ingredients for Growth

• The vision of the founding investors.–Recognize the importance of new technology in driving esoteric testing.

–Recognize that measured risk‐taking is worth a try.

–View joint ventures as positive structures for both entrepreneurs and established institutions.

Ingredients for Growth

• The support of the founding investors.–PAML support of all ancillary services to allow the scientific founders to concentrate on the science.

–Mentoring of founders in basics of business.

–Leverage relations already established by PAML and SHMC.

Ingredients for Growth

• Knowledge of the market.– Founders have been active in the clinical cytogenetics field for more than 15 years (at the time of founding the company).

–Recognize the need for innovation in technology.

–Have established networks in the field allowing early adopters to trust the new product.

Ingredients for Growth

• Knowledge of the technology.

–Prior experience in the technology.–Recognize key IP holders.–Implement key innovative step to make the product commercially viable (solve work‐flow issues, implement automation, recognize technical issues, etc.)

Ingredients for Growth

• Key hires.

–Hire talented people (technical and otherwise).

–Retain talented people.–Promote talented people (Careful how you do it!).

Ingredients for Growth

• Marketing strategy.– Trusted people with a scientifically and medically sound message.

–Publish in the peer‐reviewed medical literature.

– Founders available to the clients. All clients.

–Willing to share the knowledge.

–Offer solutions, not tests.

Ingredients for Growth• Continuous innovation.

–Innovate, innovate, innovate to stay ahead.

–Be willing to be ignorant (ignore the : “can’t be done, ‘cause no one has done it this way before).

–Use all the tools available to you (the internet is still grossly underutilized in our industry).

Signature Genomic Laboratories, LLCSignature Genomic Laboratories, LLC is the

leading diagnostic company in the field of array CGH for cytogenetic applications.

Signature offers:- a comprehensive menu of clinical array CGH platforms (BAC and oligo).- the most service options to clients.

• Genoglyphix is a comprehensive service line for cytogenetics laboratories to help them transition to array CGH.

• It is powered by a proprietary web-based application (GGX) that offers the clients the option of complete in-house testing or in-house interpretations only (Signature performs wet work).

• Since the launch of Genoglyphix in March of 2007, 12 institutions have enlisted and are actively participating.

• Microarray sales has averaged ~400 units per month and growing (sales started in June 2007).

• Additional services are being added (database access to clients, discussion forum, more platforms, etc.).

• Searchable database to assist in interpretation.

• Clients contribute to database and to the refinement and evolution of GGX application.

• FISH probes for confirmation and visualization of array results.

• A community of cytogeneticists.

Company Growth-Postnatal

Company Growth-Prenatal

Signature GenomicsMarket Share

• Market research (June 2007): Signature Genomics has >50% of the postnatal market share.

• Emerging prenatal market shows significant growth (doubled the volumes in the last 2 months).

• Signature Genomics is uniquely positioned to capture a significant portion of expanding post- and pre-natal aCGH markets.

Staying Ahead

• First to enter/create the market.• Has the largest market share.• Well-branded in the industry.• Large database of abnormals.• Choice of platforms:

WG, OS, marker, prenatal.• Choice of service:

Genoglyphix plans.

The Future

• Signature is testing many oligonucleotide platforms to further expand service and distinguish itself in the Dx market:• Agilent (44K, 105K, 244K).• Roche/NimbleGen (385K).• Affymetrix (SNP array 6.0).• Others

©2007 Signature Genomic Laboratories, LLC

The Future

• Partner with oligo manufacturers:– Signature brand, design & content– GGX interface/oligo software integration– Database access– Client support

• Partner with other product manufacturers.• Grow and diversify diagnostic service.• Develop new technologies and products.• Adopt new and emerging technologies.