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Anu Thubagere Graduate Student Fadl Saadi Graduate Student Materials Andrew Hoff Graduate Student Materials Matt Gethers Graduate Student Bioengineerin Breadagami Revolutionize Membrane Protein Crystallography Day 1: 16 Day 2: 10 Day 3: 11 Day 4: 6 Total Interviews: 42

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Anu ThubagereGraduate StudentBioengineering

Fadl SaadiGraduate StudentMaterials Science

Andrew HoffGraduate StudentMaterials Science

Matt GethersGraduate StudentBioengineering

BreadagamiRevolutionize Membrane Protein Crystallography

Day 1: 16Day 2: 10Day 3: 11Day 4: 6 Total Interviews: 42

What we thought on Day 1

Initial thoughts:• Target market would be Academics and

pharmaceutical companies who wished to do in-vitro studies

• Spatial Control main selling point

Novel Technology: Ability to tether biomolecules such as DNA/RNA/Proteins on a wafer

We can provide a scaffold onto which small molecules and biologics can be templated to allow for experiments with high spatial control.

Academics and pharmaceutical companies who want to test interactions between small molecules and biologics with high spatial control.

We provide the chip and the DNA Scaffold. The customer provides the oligo “staples” that are conjugated to the molecules of interest.

Advertising in journals. Could market services through larger supplier like Invitrogen, Sigma.

Either direct sale to customers or payment from suppliers when each chip is bought.

Must make chips. Make “master mix” that is added to oligo staples. Must maintain advertising in journals and other venues.

Access to E-beam lithography. Making master mix. Must cultivate relationships with oligo companies. Relationships with suppliers?

Oligo manufacturers. Perhaps strike agreement making chemistry conjugating molecule of interest to oligo standard part of repertoire. Perhaps they could have a pool of oligos that are used specifically for our devices.

Also need an agreement with facility that has electron beam lithography capability.

Must buy chips, constituents of master mix. Need storage facility. Need access to or need to own SEM.

Business Canvas V1

What we learned on Day 1

• Found three potential markets for our technology– Stem Cell Researchers– Cancer Pharmaceutical Companies– Protein Crystallography

• No silver bullet yet, many suggestions are for fields outside of experts’ own

We can provide a scaffold onto which small molecules and biologics can be templated to allow for experiments with high spatial control.

Academics and pharmaceutical companies who want to test interactions between small molecules and biologics with high spatial control.

We provide the chip and the DNA Scaffold. The customer provides the oligo “staples” that are conjugated to the molecules of interest.

Advertising in journals. Could market services through larger supplier like

Invitrogen, Sigma.

Direct sales

Must make chips. Make “master mix” that is added to oligo staples. Must maintain advertising in journals and other venues.

Access to E-beam lithography. Making master mix. Must cultivate relationships with oligo companies. Relationships with suppliers?

Oligo manufacturers. Perhaps strike agreement making chemistry conjugating molecule of interest to oligo standard part of repertoire. Perhaps they could have a pool of oligos that are used specifically for our devices.

Also need an agreement with facility that has electron beam lithography capability.

Must buy chips, constituents of master mix. Need storage facility. Kavli Nanoscience Institute partnership.

Eliminate uncertainty in quantity of stimulants

Simplify control of molecular orientation

Stem cell researchers

Crystallographers

Cancer pharmaceutical companies

Trade shows, Conferences, Publications, Internet

Shipping

Personal Assistance

Automated Service

Word of mouth

Yearly subscription model

Kavli Nanoscience Institute (Caltech)

Silicon Wafer Supplier

Integrated DNA Technologies

Glen Research

Product development

Shipping

Customer Service

Technical expertise

Fabrication Facilities

Business Canvas V2

What we learned on Day 2

• Interviewed 4 Protein Crystallographers– 3 of them said they were ‘not interested in our product at all’– 1 said it was very interesting for Membrane Protein

Crystallography• One third of all proteins• Very difficult to obtain crystal structure

• Started winnowing interesting fields and focusing on those where technology could have maximum impact– Removed cancer research– Ceased searching for new fields

• Started resorting to cold calls

Must buy chips, constituents of master mix. Need storage facility. Kavli Nanoscience Institute partnership.

Make crystallization faster & simpler

Stem cell researchers

Membrane Protein Crystallographers

Cancer pharmaceutical companies

Trade shows, Conferences, Publications, Internet

Automated Service

Word of mouth

Yearly subscription model

Kavli Nanoscience Institute (Caltech)

Silicon Wafer Supplier

Integrated DNA Technologies

Glen Research

Product development

Shipping

Customer Service

Technical expertise

Fabrication Facilities

Differentiate cells with much higher yield and greater reliability

Direct Sales Force

Eliminate uncertainty in quantity of stimulants

Simplify control of molecular orientation

VWR International

Direct sales

IP

Business Canvas V3

Vendor

What we Learned on Day 3

• Membrane Protein Crystallographers are good early adopters – Many have resorted to in house technology to

resolve situation– Focus of Membrane Protein Crystallography

• Specialized market limited need for Vendors• Trade shows and conferences are extremely

important in this field

Must buy chips, constituents of master mix. Need storage facility. Kavli Nanoscience Institute partnership.

Make crystallization faster & simpler

Stem cell researchers

Membrane Protein Crystallographers

Trade shows

Get: Word of mouth & Publications & Conferences

Yearly subscription model

Kavli Nanoscience Institute (Caltech)

Silicon Wafer Supplier

Integrated DNA Technologies

Glen Research

Product development

Shipping

Customer Service

Technical expertise

Fabrication Facilities

Direct Sales Force

Direct sales

IP

Keep: Customer Service

TEM Manufacturers

Grow: Cross Selling

VWR International

Problem: Crystallizing Membrane Proteins “It’s voodoo”Best case: couple monthsOften: Never

Solution:-Easy to use kit-Works for all-One tenth of the time required

Vendor

SBIR/STTR

Business Canvas V4

What we learned on Day 4

• Numbers– Time scale– Cost– Yield

“[If you can do this], it would be revolutionary…the world would be at your door”James BowieProfessor and Vice-Chair; Department of Chemistry and Biochemistry, UCLA-DOE Institute for Genomics and Proteomics and Molecular Biology Institute

Get: Word of mouth Publications Conferences

Kavli Nanoscience Institute (Caltech)

Silicon Wafer Supplier

Integrated DNA Technologies

Glen Research

Shipping

Customer Service

Fabrication Facilities

Keep: Customer Service

Grow: Cross Selling

SBIR/STTR/Angel

Current Business Canvas

Personnel

Conference Travel

Product development Problem: Crystallizing Membrane Proteins “It’s voodoo”Best case: couple monthsOften: Never

Solution:-Easy to use kit-Works consistently-One tenth of the time required

Trade shows

Direct Sales Force

Technical expertise

IP

Direct sales

Membrane Protein Crystallographers -Grad Student-Postdoctoral Scholar-Staff Scientist

Storage and Work Facility

Kavli Nanoscience Institute partnership

Consumables (wafers, oligos etc.)

We can provide a scaffold onto which small molecules and biologics can be templated to allow for experiments with high spatial control.

Academics and pharmaceutical companies who want to test interactions between small molecules and biologics with high spatial control.

We provide the chip and the DNA Scaffold. The customer provides the oligo “staples” that are conjugated to the molecules of interest.

Advertising in journals. Could market services through larger supplier like Invitrogen, Sigma.

Either direct sale to customers or payment from suppliers when each chip is bought.

Must make chips. Make “master mix” that is added to oligo staples. Must maintain advertising in journals and other venues.

Access to E-beam lithography. Making master mix. Must cultivate relationships with oligo companies. Relationships with suppliers?

Oligo manufacturers. Perhaps strike agreement making chemistry conjugating molecule of interest to oligo standard part of repertoire. Perhaps they could have a pool of oligos that are used specifically for our devices.

Also need an agreement with facility that has electron beam lithography capability.

Must buy chips, constituents of master mix. Need storage facility. Need access to or need to own SEM.

Business Canvas V1

Workflow for creating Membrane Protein Crystals

Cloning

Heterologous expression

Membrane preparation

Screening for detergents

Solubilization

IMAC purification

Gel filtration

Ion exchange Protein characterization

Crystal screening

Crystal optimization

X-ray diffraction

Our Target

Newby, Z, Nature Protocols 4, 619 (2009)

Day in the Life Diagram

Micelle + Protein + Detergent + 10 Plate Crystal Analyze StructureRobot National Lab

2 days 1-3 Months 10% Structural Information

90%

Micelle + Protein + Detergent + 10 Breadagami Crystal Analyze StructureRobot Local

equipment

2 days Days 90% Structural Information

After

Before

FailPass

Fail

Pass

10%

Total Cost: $200,000

Total Cost: $100,000

• User• Some discretionary funds• Early adopter

Grad Students and Techs

• User• More discretionary funds• Early adopter

Post-Doc

• User• More discretionary funds• Early adopter

Staff Scientist

PI• Influencer• Economic Decider• Possible Saboteur

Journal Reviewer

• Influencer• Saboteur

Funding Agencies

• Influencer•Economic Decider

Department Head

• Influencer

• ProviderReagent/Equipment Suppliers

Archetype/Ecosystem

Minimum Viable Product

Patterned chip Breadagami

BuffersOther Vendors

• Easy to use• Works with off the shelf consumables• One size fits all

2-D protein crystals

Value PropositionValue proposition: • Remove uncertainty• Order of magnitude decrease of time spent to obtain structural

information of membrane proteins• Higher research throughput • Less consumablesValue added to customer:• Old Process: Cost of obtaining structural information of a membrane

protein: $200,000 “Likely an underestimate”*

• New Process: Target cost of obtaining structural information of a membrane protein: ~$100,000 – Graduate student cost: 9 months $37,500– Consumables: $12,500– Breadagami: $50,000 (@$5,000/chip)

*Prof. James Bowie

Addressable MarketTotal Addressable Market (TAM): ~300 researchers worldwide

Served Addressable Market (SAM): ~150 researchers in USA

Current Target Market: 75% of SAM @ $60k/year/researcherEstimated sales of ~$7 million/year

Future trends: • Large increase in number of researchers & funds• New customer segments develop (pharma)

Customer Relationships

Get: Outreach with Trade Shows Conferences WorkshopsPartnering with prominent researchers

Keep: Automated, simple system for reordering Email updates on new uses of technology

Grow: Cross selling products (buffers, etc.)

Revenue Model

BreadagamiGrad Student/Tech

Post-Doc/Senior scientists

Principal Investigator

• Revenue stream: Direct Sales, • Pricing: Fixed, value, volume pricing, $5000/chip• ~10 chips for 1 crystal ie $50,000• Possible cut off limit for Grad Students & Tech

• Revenue Streams: Direct Sales• Pricing: Fixed, value, volume

Next Steps

• Talk to more Membrane Protein Crystallographers to refine value proposition

• Create prototype• Patent• Publish

What we Really Learned

• You don’t know everything from Day 1• Go and talk to potential customers• Don’t be discouraged when you get bad news• Situation is always more complex than

previously thought• Being an Entrepreneur is tough!

Acknowledgments

• Interviewees• Classmates• Charles House • Andy Sack • Ken Pickar• Jon Feiber• Steve Blank

Channel

Breadagami

Local (University) Marketplace

Customer

• Typical vendors would be Sigma, VWR, Invitrogen

• Eager early adopters• Small community

Vendor

Revenue Model

Year 1 (of sales)• Cost:

– Raw material ~$300/wafer – Lab space ~$13,000/year (1

person space)– Kavli Nanoscience Institute

~$30,000/year– Cost of personnel ~$50,000/year

• Goal: sell 100 kits in year 1 @ $5000/kit– Revenue: $50,000– Cost: $80,000– Profit: -$30,000

Year 2• Cost:

– Raw material ~$300/wafer – Lab space ~$26,000/year (2 person

space)– Kavli Nanoscience Institute

~$60,000/year– Cost of living ~$200,000/year

• Goal: sell 1000 kits in year 2 @ $5000/kit– Revenue: $5 million– Cost: $586,000– Profit: $4.4 million